Combining CBT and Medication: An Evidence-Based Approach

Combining CBT and Medication An Evidence-Based Approach



Donna M. Sudak, M.D.

John Wiley & Sons, Inc.

This book is printed on acid-free paper. Copyright © 2011 by John Wiley & Sons, Inc. All rights reserved. Published by John Wiley & Sons, Inc., Hoboken, New Jersey. Published simultaneously in Canada. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 646-8600, or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748-6011, fax (201) 748-6008. Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor author shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold with the understanding that the publisher is not engaged in rendering professional services. If legal, accounting, medical, psychological or any other expert assistance is required, the services of a competent professional person should be sought. Designations used by companies to distinguish their products are often claimed as trademarks. In all instances where John Wiley & Sons, Inc. is aware of a claim, the product names appear in initial capital or all capital letters. Readers, however, should contact the appropriate companies for more complete information regarding trademarks and registration. For general information on our other products and services please contact our Customer Care Department within the U.S. at (800) 762-2974, outside the United States at (317) 572-3993 or fax (317) 572-4002. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books. For more information about Wiley products, visit our website at www .wiley.com. Library of Congress Cataloging-in-Publication Data: 978-0-470-44844-1 (pbk) 978-1-118-07665-1 (ebk) 978-1-118-07666-8 (ebk) 978-1-118-07664-4 (ebk) 978-1-118-09336-9 (obk) Printed in the United States of America 10 9 8 7 6 5 4 3 2 1

Contents Preface

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1 Medication Versus CBT: How Did That Happen?

1

2 Neurobiological Evidence and Combined Treatment

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3 Dual Responsibility Treatment: Principles That Facilitate Collaborative Patient Care

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4 Combining CBT Interventions and Medication to Enhance Medication Adherence

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5 Combined Treatment for Major Depression

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6 Combined Treatment for Bipolar Disorder

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7 Combined Treatment for Anxiety Disorders

103

8 Combined Treatment for Eating Disorders

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9 Combined Treatment for Schizophrenia

139

10 Combined Treatment for Borderline Personality Disorder

159

11 Combined Treatment in Pregnancy

181

12 Combined Treatment for Substance Abuse and Dependence—written with Samson Gurmu, M.D.

193

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Contents

References

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Author Index

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Subject Index

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Preface

P

ractitioners are equipped with a variety of treatments for the most common psychiatric disorders. Unfortunately, there is little clear-cut evidence to help with the choice between treating with medications, psychotherapy, or both. Researchers have found that cognitive behavioral therapy (CBT) and pharmacological treatments for psychiatric conditions are effective for a number of diagnoses, but less evidence is available about how to determine what sequence or combination of treatments would be best to help a particular patient recover and stay well. Mental disorders are widespread, painful, and expensive. A patient’s well-being hinges on a durable and complete recovery. Once treatment starts and a patient is stabilized, it is even more complicated to decide when, how, and in what sequence to withdraw treatment. Practitioners are also charged with delivering the most cost-effective, efficient care. Ideally, when data exists, mental health providers should systematically approach problems in clinical care and recommend a sequence or combination of treatments that is safe, effective, efficient, and durable. Health care costs and human suffering make this an imperative part of clinical work. What generally occurs in practice is that treatment decisions are determined by a combination of factors including patient preference and diagnosis, therapist comfort, access to prescribers and/or qualified psychotherapists, acuity and severity of symptoms, and financial resources. Many patients who enter therapy have already been prescribed medication by a primary care physician. In fact, one study found that 95% of patients with panic disorder in the US seek treatment from their primary care physician first before obtaining a referral to a psychiatrist (Craske & Rodriguez 1994). Between 55 and 95% of patients with anxiety disorders are already on medications at the time they seek therapy (Wardle 1990). Waikar and colleagues (Waikar, Bystritsky, Craske, & Murphy 1994) studied patient attitudes and beliefs about medication and determined that patients prefer to receive combined treatment. Residency training programs in psychiatry and, to a lesser extent, in primary v

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care specialties have increased requirements for residents to be trained in both modalities. Thus, combined treatment is often the rule and not the exception. Another reason to consider combining medication and psychotherapy is that patients on medication often continue to have residual symptoms or will relapse despite continued use of medication or participation in therapy. We have some data about residual symptoms in mood disorders that indicate that patients who have residual symptoms have a greater vulnerability to relapse. Adding a second treatment may make full recovery more likely. Combined treatment could reduce costs by broadening the scope of treatment effects and increasing the rate of response. Some patients who are in a single treatment who could benefit from a combination of treatments are not inclined to seek pharmacological treatment because of biases against physicians or medication. Therapy could be useful to these patients to help them examine the attitudes they have and perhaps make medication an acceptable option. Finally, patients in psychotherapy have a greater awareness of pharmacotherapy options because of the impact of advertising and the Internet. The quality of the information they obtain can influence the acceptability of combined treatment, so a well-informed therapist is essential. The purpose of this book is to provide a review of the evidence currently available about combining medication and CBT. It begins with an overview of the research methods in existing studies of combined treatment in Chapter 1, and a review of the current neuroimaging and neurobiological studies that could influence our understanding of how the combination of treatments work in Chapter 2. Combined treatment can be delivered by a single provider, or by a therapist for psychotherapy and a prescriber. Chapter 3 will describe the potential advantages and pitfalls of providing “collaborative treatment,” a term coined by Riba & Balon (1999)—that is, treatment by a psychotherapist and a prescriber. The original definition they provided denoted a psychiatrist as a prescriber, but the term could apply to a primary care physician or nurse practitioner as well. Clinical vignettes will illustrate strategies to enhance collaboration and to avoid the ethical dilemmas that can arise in collaborative treatment. This chapter will also discuss how to exploit the advantages of having two caregivers. In addition, because thoughtful and deliberate implementation of combined treatment can be a challenge in complex patients, Chapter 4 will present a model for integrating pharmacotherapy and CBT that enhances adherence to the two approaches whether therapy is given by single or multiple care providers.

Preface

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The remainder of the book details specific evidence for or against combining treatment in particular disorders, and, in the case of Chapter 11, during pregnancy. The book is not designed to review all the diagnoses that are encountered in clinical practice, but to focus attention to the most common clinical presentations for which there is evidence as to how to proceed with both treatments. Chapters are designed to review the evidence and to discuss specific challenges in combined treatment with the particular disorder. Chapter 5 and Chapter 6 present evidence for combined treatment in two debilitating mood disorders—major depression and bipolar disorder. Each of these chapters focuses on specific clinical characteristics that can benefit from collaborative care as well as the evidence for better outcomes when CBT is combined with medication. These chapters, along with Chapter 8, which addresses schizophrenia, pay particular attention to suicidal behavior and managing this difficult clinical problem when there are two treatment providers. Chapter 7 explores the evidence available for combining CBT with various medications in anxiety disorders. Principles that facilitate consistent communication to anxious patients in dual-responsibility treatment are presented, along with clinical vignettes that illustrate key concepts. The next three chapters share a common demographic group—women of childbearing years. Chapter 9 reviews collaborative care in eating disorders. This group of patients requires collaborative care even if psychotropic medication is not prescribed, because of the need for dual responsibility in conjunction with a primary care physician or pediatrician. A similar discussion is contained in Chapter 11, Combined Treatment in Pregnancy. Pregnancy does not protect women from psychiatric illness, and the principles of collaborative care are essential in the care of women who wish to become pregnant and need to manage a chronic mental illness. Chapter 10 discusses combined treatment for patients with borderline personality disorder, a condition that is frequently challenging to navigate with multiple care providers. The final chapter, Combined Treatment for Substance Abuse and Dependence, is somewhat different from the previous chapters. It includes more detailed information about the medications available to use in combination with cognitive-behavioral interventions. Many practitioners are unfamiliar with the newer drugs that are available; they can be helpful adjuncts in these common and debilitating conditions. This chapter was co-written with Samson Gurmu, M.D., a talented chief resident at Drexel University College of Medicine, whom I have the pleasure of supervising. His passion for studying

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and treating substance-use disorders was an impetus for this chapter’s inclusion. I am grateful to him for his participation and hope to see his name in print with great frequency in the years to come. Although several evidence-based forms of therapy are classified as CBT (for example, problem-solving therapy, cognitive therapy), the CBT referred to in the text is the version elaborated by Aaron T. Beck. Additionally, the clinical cases presented are fictitious and represent examples of common clinical situations. They are designed to illustrate the opportunities and challenges that present to most clinicians. I have also used the convention of alternating pronouns (he and she) for readability. I have used the terms patient, therapist, and prescriber, with the knowledge that other practitioners have different conventions and philosophies about such terms. I am aware that the role of prescriber often entails much more than pharmacological expertise, and that patient is frequently a term that is regarded as less apt for individuals in mental health treatment. Many people assisted in the completion of this book. I owe a great deal to Cheryl Carmin, Irismar Reis De Oliveira, Wei Du, Kelly Koerner, Joan Romano, and Deborah Gross Scott for their helpful suggestions. My residents, supervisees, and patients inspire and motivate my work every day. Patricia Rossi at John Wiley has been an unfailingly persistent and patient editor. Finally, I am tremendously grateful for the love, support, and accurate feedback from my husband and most respected colleague, Howard Sudak, and the unshakable good humor, confidence, and fast fingers of my daughter and world-class word processor, Laura Ferguson.

Combining CBT and Medication: An Evidence-Based Approach by Donna M. Sudak Copyright © 2011 John Wiley & Sons, Inc.

CHAPTER

1 Medication Versus CBT How Did That Happen?

M

ary is a 40-year-old woman who has been in therapy for six months for a severe depression, which developed after her husband of 15 years left her for another woman. Unfortunately, her depressive symptoms include fairly routine and significant insomnia—she wakes up at four a.m. nearly every night. The sleep disturbance has been not responsive to her therapist’s suggestions to make her bedtime and waking time the same each day and to employ other sleep hygiene measures. Mary is a pharmacist in a busy chain-operated drugstore. She is in danger of being fired because her work performance has been altered by fatigue and poor concentration. Her therapist is reluctant to refer her for a medication evaluation because she believes Mary’s depression has such a clear-cut psychological precipitant. John is a 60-year-old man who was recently diagnosed with lung cancer. He has developed fairly significant anxiety about an impending surgical procedure to remove the lobe of his lung that contains the primary lesion. He has suffered multiple panic episodes, and in the past month he has started to avoid going out to the mall or to football games. His primary care physician prescribes Clonazepam 0.5 mg twice a day and tells John that it “makes sense” that he would be anxious given his circumstances. He does not refer John for therapy. Mary and John are both in treatment with practitioners who have beliefs about the origins of their patients’ illness that influence the treatment they provide. The decisions we make as clinicians are informed by our understanding of the nature and best available treatment of particular psychological problems. Most of us have a view of combined treatment with medications and CBT that is influenced by how research studies of combined treatment were 1

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Medication Versus CBT

conducted in their earliest iterations. It helps to retrace some of this history to assess the quality of the data we use to make clinical decisions.

STUDIES OF COMBINED TREATMENT Studies conducted about treatment combining medications and CBT evolved with the aim of establishing comparative efficacy. A tremendous increase in effective novel medications for depression and anxiety occurred in the 1960s and 1970s. Although it is an imperfect system, the development of the Diagnostic and Statistical Manual of Mental Disorders (DSM) meant that researchers were able to make clearer distinctions between groups of patients and actually determine what treatments worked in particular disorders. Structured interviews became available that increased the consistency of diagnoses in patients—so that more homogeneous and accurately diagnosed groups of patients could be studied in either medication or psychotherapy treatment trials. This was a major advance in the field and increased the ability to develop and test new treatments. Once an accurate diagnosis was made, clinicians could treat patients with greater effectiveness. The previously mentioned explosion in biological treatments was paralleled by substantial new knowledge about manual-based psychotherapeutic treatments— such as CBT and interpersonal therapy (IPT)—that could rapidly and effectively work to treat major depression, panic disorders, and phobias. Medications were considered the “gold standard” as a treatment approach; psychotherapy was evaluated for comparative efficacy. Most research trials were conducted to determine whether individual treatments worked. Unfortunately, investigators who considered the question of whether these treatments were effective were generally quite invested in the approaches they evaluated. Thus, they often framed questions that were inadvertently biased to favor the form of treatment that they espoused. For example, many of the studies that evaluated the efficacy of medication treatment for panic disorder versus the efficacy of CBT were done with patients who did not display agoraphobic avoidance. This would naturally dilute the efficacy of exposure-based procedures in the CBT provided. Certainly the outcome measures chosen to evaluate what constituted response in any study of combined treatment would influence what view we had about the utility of either approach and for which groups of patients. Research about the positive and negative effects of combined treatment was rarely performed in these early comparative studies. Process research that

Studies of Combined Treatment

3

could inform us about any differential effects of medication or therapy or their combination in particular types of patients is still largely uncharted territory. Pooled data that are evaluated at the end of treatment do not allow us to determine individual differences in response to combined treatment over time. Such studies would be expensive and complicated. Early studies considered outcomes at the end of therapy without any effort to look at process issues, interactions between treatments, or specific patient variables that would make patients more suitable for one particular approach or the combination. As treatments became more effective, it became more difficult to determine if the combination of two treatments would be even more powerful than either treatment alone. Highly effective treatments require very large studies to determine whether any benefit is derived from their combination. The expense and complexity of such studies limit the frequency with which they occur. Because medication and therapy independently have a substantial impact relative to placebo in depression and anxiety, there is less incentive to conduct complex and costly evaluations of the beneficial or deleterious effects of the combination. Early studies of combined treatment for depression were small, but had some nonsignificant trends toward an increased response rate for those patients who received combined treatment. At least one large-scale clinical trial (Keller et al., 2000) indicates a fairly substantial benefit from combining a form of CBT with medication versus either treatment alone in a group of chronically depressed patients who had a limited response to prior treatment. Ideally, a heterogeneous group of investigators should develop and execute combined treatment research and pool expertise so that process variables could be measured in the widest possible manner. Gorman and his colleagues (Gorman, Barlow, Ray, Shear, & Woods, 2001) detail the complexity of such a collaboration in an article describing the work they did in evaluating the differential efficacy of CBT, imipramine, and CBT combined with imipramine for panic disorder. Several recent studies, for example, the Treatment for Adolescents with Depression (TADS) study (March et al., 2009), were similarly well designed. They were developed by a multidisciplinary team of investigators and will likely increase our knowledge about variables that influence positive patient outcome. In the context of the early “horse race” model designed to evaluate the differential efficacy of medications, therapy, or both, many of the completed and published studies evaluate combined treatment with medications that are currently not in common use. A majority of the studies in depression and

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Medication Versus CBT

anxiety investigate the efficacy of tricyclic antidepressants alone, compared to, and in combination with CBT, for example. Unfortunately, the data we have from these studies has limited applicability to current practice. The vast majority of patients do not take these medications for depression or anxiety because of the debilitating side effects and risk of suicide inherent in their use. There is less incentive to pursue combined treatment research with newer medications, because CBT has been established as an effective treatment for depression and anxiety and newer antidepressants have not been found to be more effective than tricyclic antidepressants, so that testing them head-to-head with CBT and evaluating the combination has less value to researchers. Another limitation to generalizing the research data available about combined treatment to clinical practice is that research studies do not employ optimal or acceptable standards of care. Separate clinicians deliver each treatment in research studies with minimal, if any, communication with one another. Medications in most clinical trials are prescribed with limited dosage adjustments, if at all. If there is no response, research protocols prohibit switching or augmenting medications. Patients generally continue on the same medication for the full duration of the study, regardless of their response, when in clinical practice another method of treatment would be added if medication was ineffective. Pharmacotherapy protocols in research studies generally do not allow for any addition of pharmacological treatments for debilitating and common symptoms when they are incompletely treated by the prescribed medication. Insomnia or severe anxiety would typically be managed by additional medications in the acute treatment of a severely ill patient. Providers who prescribe in research trials are often instructed to limit the interpersonal interactions they have with patients to reduce any study error caused by variation in therapy time. Murphy and colleagues (Murphy, Carney, Knesevich, Wetzel, & Whitworth, 1995) have shown that antidepressant medication is far less effective when providers are instructed to not interact with patients in a positive and engaged way—largely because of adherence issues. In a meta-analysis, Pampallona and colleagues (Pampallona, Bollini, Tibaldi, Kupelnick, & Munizza, 2004) determined that 33% of patients in treatment with antidepressants who are not provided therapy drop out of treatment and do not take medication. Gorman and colleagues (2001) describe a situation in the combined treatment study of CBT and imipramine in panic disorder in which one practitioner had an unusually low response rate to the medication provided. Upon review, this practitioner was interacting minimally with patients because of his concern

Studies of Combined Treatment

5

that he could confound the study results by providing additional therapy. Therefore, medication treatment provided with minimal interaction with care providers may not accurately reproduce clinical outcomes with optimal care. Therapists with a positive attitude toward medication can enhance the placebo response to medication (Barrett & Wright, 1984). This potentiating effect is absent in blinded combined treatment trials. In the psychotherapy arm of research projects, therapy is often unlike clinical practice. It is generally manual-based with less emphasis on individual patient conceptualization. Patients are assessed with multiple measures throughout treatment—which could alter patient expectations and motivation in a positive or negative way. If patients have co-morbid Axis II psychopathology, there is rarely the flexibility to slow the therapeutic process to allow for the type of alliance-building that is necessary to employ CBT effectively. Another difficulty we face in determining the best evidence-based option to recommend to a patient is that patients who are eligible to participate in clinical trials represent a very narrow spectrum of the individuals afflicted by a particular diagnosis. An estimated 80% of applicants to antidepressant trial research are excluded (Posternak, Zimmerman, Keitner, & Miller, 2002). Zimmerman and his colleagues (Zimmerman, Mattia, & Posternak, 2002) looked at the medical records of patients seen in a large general psychiatry clinic to see how many of them would be eligible for a clinical trial of antidepressant medications. Of 803 patients, 346 had major depression. Of these patients, 86%—all but 41—would be excluded from a typical efficacy trial due to co-morbidity, chronic illness, severity, or suicidal ideation. Patients seen by therapists and prescribers in routine clinical practice are often far more complicated and have more chronic conditions than those who participate in clinical trials. Bockting and colleagues (2008) determined that patients with greater numbers of episodes of illness derive the most benefit from combined treatment—again, these patients were often excluded from early efficacy trials. The complexity of the typical patient who seeks mental health care makes it more difficult to determine what treatment makes sense; studies of patients with co-occurring disorders are even scarcer. Patients who respond to treatment in typical efficacy trials may be very different from the typical patient who seeks treatment, accepts and adheres to treatment, and recovers and stays well. In summary, the research evidence that we have available to us about when combined treatment might be helpful has limits to its clinical applicability and may not reflect the potential benefits or detractions of combined treatment in

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Medication Versus CBT

a particular patient. What may help us best is to consider the combination of genetic/biological, interpersonal/developmental, and temperamental risk factors that any patient has in order to determine who might benefit from combined or sequenced treatment until we have better data to help us to make determinations about what would constitute optimal care. Newer practical clinical trials will hopefully help us to determine the best interventions to help a patient obtain and sustain a full recovery.

WHAT MECHANISMS COULD INFLUENCE COMBINED TREATMENT EFFECTS? We can generate hypotheses about the possible effects of combined treatment by considering the mechanisms of action of the individual effects of medications and psychotherapy. To benefit from psychotherapy, patients must be able to learn. Wright (2003) details the ways that medication or psychiatric illness could each alter attention, memory, and the ability to integrate new information. We know that a substantial number of psychiatric disorders interfere with the acquisition and retention of information. Severe anxiety, depression, mania, and psychosis, for example, can hamper normal learning. Sleep problems are common in major psychiatric disorders, and insomnia can decrease the capacity to learn and remember. Distractibility is common to many Axis I disorders—rumination, hallucinations, flight of ideas, and attention to threat can interfere with patient attentiveness. The speed of thought can be accelerated or decreased by mood disorders, hindering attention and recall. Therapy can proceed more effectively if these impediments to learning are addressed by pharmacotherapy. CBT, in particular, is primarily a treatment that relies on the patient’s ability to learn new skills, so a fundamental requirement is that patients must have the ability to learn and to remember. The downside can also be true—combined treatment has the potential to impede learning and memory. Prescribers must be aware of medications that can sedate patients and interfere with learning. Anticholinergic side effects were once a predominant feature of medications used for depression and psychosis. This particular side effect could interfere with new learning and memory functions in all patients. Specific side-effect profiles of many tricyclic antidepressants listed possible alterations in memory, including problems with word-finding. This type of alteration in memory could slow therapeutic progress. Benzodiazepines can also impair learning and recall, so when they are used for

What Mechanisms Could Influence Combined Treatment Effects?

7

anxiety, they could interfere with exposure treatment by preventing new learning as well as habituation. So a practitioner may ask “Why is this important? If medication and therapy are each so effective, what difference does it make?” And the answer—obvious to anyone in clinical practice for very long—is that our treatments, although better than ever, are still not that good. In the best hands, response to a singlemodality treatment for depression in the limited, uncomplicated population studied in most clinical trials is a bit better than 50%. Our treatments are better than placebo, but many patients do not respond. Mental illness is dangerous, painful, and debilitating. We need to consider the costs of treatment and deliver it as efficiently as possible in real-world settings. In standard clinical practice, a good clinician faced with an unresponsive patient would try to obtain better results by changing medications or therapy type or by combining treatments. Results from the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) pharmacotherapy are concerning regarding initial treatment response. STAR*D trial (Gaynes et al., 2009) was a large practical clinical trial where entry criteria were broadly defined and inclusive and patients were enrolled from psychiatric and primary care clinics. The results of this trial emphasize that antidepressant treatment is unlikely to be effective if a patient does not respond to the initial medication prescribed. In the “real world,” patients with no response after two vigorous medication trials have a very low probability of recovery from depression. Patients who do not attain a remission of depression with typical medications would likely require more complicated medication regimens with complicated side effects. These more complicated treatments have less certain success. If one could improve the likelihood of an initial response to medication by adding CBT to medication it could have a substantial impact on the course of the illness. In addition, the STAR*D trial showed that 67% of those patients who responded to medication also had residual symptoms of depression (Trivedi et al., 2006)—these continual symptoms could represent a significant burden for a patient, a risk factor for relapse, and be an additional indication for and benefit from combined treatment. Another reason to consider combined treatment is that existing pharmacological treatments for depression and anxiety do not produce a durable recovery over time, both when taking medication and once medication is withdrawn. Relapse in psychiatric illness is more the rule than the exception. Initial hypotheses offered to account for frequent relapse often included nonadherence

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Medication Versus CBT

to medication treatment, particularly in those patients who were treated with earlier medications that had undesirable side effects. Paykel (2007) did a prospective study of patients who were hospitalized for depression and who had recovered. Over a ten-year period two-thirds of patients had a recurrence, half of these within 24 months of recovery. The follow-up data the study obtained included subject interviews, prescription records, and antidepressant blood levels. These indicated that patients in the study had good adherence and still relapsed. Combined treatment may have the potential to increase coping skills in a patient with a significant genetic diathesis for depression so that they are more capable of sustaining a durable recovery. Clinicians face a number of other challenges in the “real world.” We must provide a credible rationale for our recommendation of different treatments to patients. Our interventions must be acceptable and understandable to the patient to ensure adherence. The goal of treatment should be a durable recovery (not just improvement) whenever possible. We do not reach this goal at present for too many of our patients. Treatment resistance is common and partial response is more common. Patients with co-morbid disorders and chronic illness are also those who do the least well with a single method of treatment. They are the patients who, intuitively, would be most responsive to combined treatment.

Combining CBT and Medication: An Evidence-Based Approach by Donna M. Sudak Copyright © 2011 John Wiley & Sons, Inc.

CHAPTER

2 Neurobiological Evidence and Combined Treatment

M

ost practitioners have had the powerful experience of seeing profound changes occur when patients with severe, often life-threatening mental disorders are treated with medications or psychotherapy. Each modality has the potential to reduce painful emotional states, decrease dysfunctional patterns of thought, and modify longstanding beliefs and dysfunctional behavior. Each modality can modify physiological responses that undermine effective coping and action. The mechanisms by which psychotropic medications and psychotherapy produce these powerful actions have only recently begun to be understood. Psychiatric disorders do not produce gross defects in the brain, so they are difficult to study with conventional neuroimaging techniques such as MRI or CT scans. Much of what we know about the actions of medications and therapy in the brain is derived from noninvasive means of studying brain function and neural circuits. We only have a small amount of data from these relatively new imaging techniques because they are expensive and complicated to administer. Preliminary studies using these technologies, however, give us some clues about the biological effects of psychotherapy and psychotropic medications and may inform us about the use of combined treatment in patients with mental illness. An additional benefit of this information is that it can help us better explain to patients how medications and therapy work in a more persuasive way than “we don’t really know.” The fact is, it is difficult to study the brains of living people and have them stay alive—and when we study brains in living patients, the brain is a dynamic, not a static, system, constantly changing in response to the internal and external demands

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Neurobiological Evidence and Combined Treatment

placed on the person being studied. The purpose of this chapter is to try to summarize some of the neurobiological evidence that exists about medication and psychotherapy and to apply that evidence to the question of combining treatment.

HOW MEDICATION AND PSYCHOTHERAPY CHANGE BRAINS Neurobiological evidence has begun to give us a better understanding of how psychotherapy and medications may differentially affect the brain. Both medication and psychotherapy have individual mechanisms of action that could alter brain structure and function and produce lasting change in patients’ symptoms. Kandel (2001) described evidence of new neuronal pathways that developed in the central nervous system (of sea slugs, but one would assume humans would be at least as smart) when new learning occurred. Presumably, cognitive behavioral psychotherapy, because it is based upon learning new skills and tools, would produce changes in neuronal pathways. These changes would be mediated by gene expression and induce changes in synaptic strength and numbers that could durably facilitate recovery. Medication is presumed to stimulate gene expression in the brain via synaptic receptor blockade and second messenger activation, and thus facilitate neuroplasticity and new neural pathways (Li et al., 2008). Our understanding of how these mechanisms produce recovery is rudimentary. Newer neuroimaging studies show particular and distinct patterns of change in brain function that occurs after successful recovery following treatment with medication or psychotherapy. These brain changes occur in similar patterns in some diagnoses; and in different patterns in other diagnoses. Neuroimaging studies might help us choose to study combined treatment if they discover that each individual treatment has a different mechanism of action in a particular diagnosis and could potentially act synergistically. Our excitement about neurobiological evidence of brain changes that occur after effective psychological and biological treatment must be tempered; these are early, crude measures of what is occurring in the brain. One hundred years from now scientists may be laughing about the theories we had about what these findings mean and the technologies we used. They may consider our treatments to be as gross as trephination seems to neurosurgeons now.

Neuroimaging: The Good, the Bad, and the Ugly

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NEUROIMAGING: THE GOOD, THE BAD, AND THE UGLY Despite the remarkable advances in evaluating brain function with neuroimaging techniques, several caveats exist in examining this evidence. First, the number of patients examined with this technology is small. Second, there is a very small number of studies. Studies rarely include normal controls, and imaging protocols are not standardized across studies. Imaging studies also most frequently measure blood flow or brain metabolism, but they do not correct for volume of brain tissue (Drevets, 1998; Linden 2006), do not actually quantitate change in blood flow, and do not calculate the actual amount of difference in brain metabolism. In addition, we know that prior pharmacotherapy can alter blood flow to particular brain regions. Without a comparison pretreatment (drug-naïve) brain scan, subsequent treatment with antidepressant, antianxiety, and antipsychotic agents could confound results (Drevets, 1998).

How Neuroimaging Is Performed The two main physiological changes currently measured to indicate changes in brain function and activity are changes in blood glucose utilization and blood flow that occur before and after treatment. These physiological changes are measured with three different types of imaging technology: PET (positron emission tomography) and SPECT (single photon emission tomography) scans and fMRI (functional magnetic resonance imaging). A brief description of the technology involved follows; readers who are familiar with the techniques can skip forward to the review of the studies available. Readers who are more interested in the technical aspects of the scanning procedures in current use may refer to an excellent summary by Seibyl, Scanley, Krystal, and Innis (2004). PET and SPECT are similar types of radiological scans. PET and SPECT scans are obtained by replacing an element contained in a biologically active molecule with a radioactive tracer. Areas of greater or lesser metabolic activity are then differentially visible by the scanner when the tagged molecule is taken up in greater concentrations in more active cells. A specific characteristic of nerve cells is that they do not store or produce energy, in the form of glucose. This means that when metabolic activity increases in an area of the brain, neurons depend nearly entirely on the transport of glucose to them from the blood flow from neighboring capillaries. So increased nerve cell activity produces increased metabolism and requirements for glucose in nerve cells. The body

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Neurobiological Evidence and Combined Treatment

responds by significantly changing blood flow so that more glucose molecules are transported to that area of the brain. PET and SPECT scans measure these changes either of blood flow or of glucose uptake. In a SPECT or PET scan, the invasive part of the process is that the patient is injected with a radioactively tagged molecule. Radioactive technetium-tagged hexamethyl-propyleneamine oxime is used in SPECT scans and radioactive fluorodeoxyglucose is used in PET scans. While the patient’s brain is scanned the radioactive isotope gives off photons as it decays in the body. A computerized tomography camera is used to obtain images of the radiographically tagged brain, but unlike CT X-rays, these cameras measure photons emitted by the decaying radioisotope in the patient. Basically, computerized tomography cameras work by making multiple X-ray images of an organ at regular distances. The scanners then reconstruct the images with computer technology to form images of the scanned body part. Quantitative data about the intensity of the photon signal is also used to generate data about the activity of the brain region. PET and SPECT scans have some important differences. There are limits to the anatomical data visible on PET scans. PET scanners can be combined with MRI scanners to combine simultaneous metabolic and anatomic pictures and therefore pinpoint what structures in the brain are more metabolically active. Another significant limitation to PET scanning is that the radioisotopes required to visualize brain metabolism have very short half-lives. The benefit of this to the patient is that it limits the radiation dose received by the patient (and since measuring brain activity in this way involves targeting a molecule—glucose— used by every cell in the body, the exposure to proton emissions is widespread in PET scans). The disadvantage of the short half-life is that the radioactivity of the tagged glucose molecule decays so rapidly that testing facilities must have a cyclotron close by to produce the isotope. This is very expensive and limits the affordability of the technology to larger research facilities. SPECT imagery, on the other hand, employs a gamma camera to scan a patient. The radioisotopes that are injected emit gamma rays, and images are obtained. SPECT scanners use more easily obtained isotopes, which are taken up by tissue proportionate to brain blood flow. SPECT scans are therefore somewhat less precise, but less expensive. An additional drawback of SPECT imagery is that patients must not move while the scan is taken (generally for more than 30 minutes). Functional magnetic resonance imaging (fMRI), the third most popular type of scan, measures changes in blood flow and blood volume. Most fMRI

Neuroimaging: The Good, the Bad, and the Ugly

13

research available at present has been designed to look at areas of increased brain blood flow that occur as the patient performs a particular task (Linden, 2006). fMRI scans are images produced when a magnetic field is created in the molecules of water in the body. First, a strong magnet aligns the hydrogen atoms in the body. Then, radio frequencies are used to change the alignment of the hydrogen atoms in the molecules of water. This process creates a magnetic field that is detected by the machine. No radiation is used. Tissues produce detectable and different frequencies depending on their protons’ magnetic state. fMRI scans can also be performed with injectable contrast material. A number of images (usually one per second) are taken and reconstructed into a three-dimensional image of the brain. Thus, fMRI scans the brain rapidly and repeatedly to measure increases in blood flow before and after a specific task. One particular type of fMRI is designed to look at brain activation without the need for contrast material by evaluating blood oxygenation on the scan (BOLD: blood oxygenation–dependent imaging). Again, we assume that changes in blood flow and blood oxygenation correspond to increases and decreases in neural activity and brain function. A disadvantage of fMRI is that the patient must lie motionless for a long period (generally at least one hour) while performing specific cognitive tasks or while at rest. Now that we have reviewed how these scans are performed, here is a brief review of current neuroimaging data about the neurobiological effects of medication and therapy across classes of disorder.

Neuroimaging Results in Psychiatric Disorders Anxiety Disorders Etkin and Wager (2007), in a review of the existing literature on functional neuroimaging in anxiety disorders, describe that in the untreated state, individuals with post-traumatic stress disorder (PTSD), social anxiety disorder (SAD), and specific phobia (SP) had greater metabolic activity in the amygdala and insula. This pattern of increased activity in the amygdala also occurs in normal subjects after fear conditioning. In addition, they describe unique patterns in PTSD that involve hypoactivation in the anterior cingulate cortex and ventromedial prefrontal cortex. A current theory is that one of the clinical manifestations of this hypo-perfusion is a problem with emotion regulation in PTSD patients. The Etkin and Wager review was a meta-analysis of existing studies to attempt to compensate for the lack of statistical power given their

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Neurobiological Evidence and Combined Treatment

very small sample sizes. The review highlights the problems cited earlier—many of the studies to date have inconsistent and variable design features, and all have very small numbers of patients. Despite the methodological problems, a fairly consistent pattern of activation occurs in untreated anxiety in PTSD, SAD, and SP that correlates nicely with existing treatment studies that indicate a normalization of blood flow in recovery. Studies of the metabolic changes in the brain in patients with obsessive compulsive disorder (OCD) and specific phobias treated with CBT or selective serotonin reuptake inhibitors (SSRIs) also yield fairly consistent results. Neural pathways change similarly with successful response to either treatment. In OCD, hyperactivity of the right caudate occurs with symptom provocation or when imaging occurs in the untreated state. In patients successfully treated with exposure and response prevention or SSRIs, right caudate and thalamic blood flow decreases in treatment responders (Baxter et al., 1992; Schwartz, Stossel, Baxter, Martin, & Phelps, 1996). In fact, the percentage that orbitofrontal cortex metabolism normalizes predicts response to both exposure and response prevention and medication (Brody et al., 1998). In SAD, amygdala and hippocampal activation on a PET scan occurs with symptom provocation, and this hypermetabolism stops after treatment with SSRIs or CBT (Furmark et al., 2002). An interesting use of fMRI has been evaluating brain function in phobic patients (Paquette et al., 2003). When the brain of a patient with a phobia is presented with a feared cue, a discrete stimulus has occurred with a measurable brain reaction. Activation occurs in the right dorsolateral prefrontal cortex and parahippocampus when the cue is presented before treatment, and this activation resolves after successful treatment.

Major Depression In addition to SPECT, PET, and fMRI studies, there have been a few studies that indicate that several other biological markers change in depressed patients who recover after CBT treatment compared to patients who do not respond to treatment. These studies increase our confidence that patients who receive psychotherapy have had a procedure that changes the biological processes that occur in major depression. Thase and colleagues (Thase, Fasiczka, Berman, Simons, & Reynolds, 1994) noted that patients with depression who had a successful recovery with CBT had a renormalization of REM sleep density that paralleled the change in patients treated with medication. Joffe, Segal, and

Neuroimaging: The Good, the Bad, and the Ugly

15

Singer (1996) found that thyroid-stimulating hormone decreased after patients with depression responded to CBT but increased in nonresponding patients. Baseline neuroimaging in depression has shown some fairly consistent findings. Patients who are depressed have decreased activity on PET and SPECT scans in the dorsolateral prefrontal cortex. These changes correlate with symptom severity (Sackheim, 2001). After treatment, scan results have been far more variable. Explanations of this phenomenon have included sample variability and size, lack of quantitative data, and the diversity of symptom patterns in depression (Linden, 2006; Sackheim, 2001). In truth, we also are not clear about what the changes in brain activity in depressed patients at the time of recovery represent—they could indicate a predisposition to future depression in the recovered state, or they could represent the result of recovery from a mood disorder. Two studies of depressed patients treated with medication or psychotherapy (Brody et al., 2001; Martin, Martin, Rai, Richardson, & Royall, 2001) found that resting prefrontal hypo-perfusion renormalized after depression remission with paroxetine and CBT (Brody et al., 2001) and with venlafaxine and interpersonal therapy (IPT) (Martin et al., 2001). Important differences existed between these studies, however, with one group indicating an increase in basal ganglia activity (Brody et al., 2001) and the other group a decrease in this activity after successful treatment (Martin et al., 2001). The severity of depression in the groups was different, which could be one reason accounting for the differences; also, different medication was used and different forms of psychotherapy were employed. These inconsistent results may also be an indication that we are in the earliest stages of being able to recognize what patterns exist and what they mean. Goldapple and colleagues (2004) also found that the response to pharmacologic treatment and CBT had distinct and different regional change patterns—a small study of 17 patients who responded to pharmacotherapy with paroxetine had increases in metabolism in the left dorsolateral prefrontal cortex and decreased metabolism in the hippocampus, while unmedicated patients who responded to CBT had an opposite pattern (Goldapple et al., 2004). Of note is that six of the patients in this study were drug naïve at the time of scanning. This pattern led to the proposal of the “top-down, bottom-up” theory—that is, that brain stem and thalamic changes occur with medications and cortical changes occur with CBT, each uniquely remedying deficits that occur in depression. The significance of this as regards combined treatment

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is that there may be specific subgroups of patients who respond best to a single modality or who require both types of treatment to sustain a remission. Kennedy and colleagues (2007) had yet a different set of findings in a randomized study of venlafaxine and CBT. Both groups of responders had decreases in metabolism in the dorsolateral prefrontal cortex, but different effects in responders to either medication or CBT in the basal ganglia and cingulate cortex. Frewen, Dozois, and Lanius (2008) reviewed the existent literature about neuroimaging in psychotherapy with the goal of linking the psychotherapeutic intervention and mechanism of change to specific neural correlates. For example, they link the skill-training function of CBT and IPT that is designed to enhance coping, problem solving, and interpersonal functioning to an enhanced functioning of the dorsolateral prefrontal cortex, an important mediator of working memory and cognitive functioning. They suggest that, since particular neural pathways have been identified that could impact mood and anxiety disorders, neuroimaging could be an investigative tool employed in a hypothesis-driven fashion to give us more information about how therapy and medication change function in particular pathways. This review notes that despite the positive trend in delineating brain changes produced by therapy, the limitation of very small sample sizes is clear, and inclusion of nonpsychiatric and wait-list control groups need to be added to remove any neuroimaging changes produced by the nonspecific therapeutic effects of the treating relationship. Additionally, emotion regulation and neuroimaging correlates of positive change produced by treating psychiatric disorders could occur by other mechanisms and neural pathways, as postulated by Taylor and Liberzon (2007). Other effective psychotherapeutic systems could impact upon different neural circuits to induce change. Dichter and his colleagues (2009), for example, used fMRI to study a group of patients with major depression treated with behavioral activation compared to normal controls. There were significant improvements in the patients’ post-treatment with respect to enhanced responsiveness in reward centers in the brain, particularly in the anticipation of rewards.

Future Directions Because psychiatric disorders are not illnesses that arise from a single gene, neuroclinical abnormality, or place in the brain (Mayberg, 2006), one can postulate that different modes of treatment could change different parts of the brain. As we become more sophisticated in understanding how particular

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illnesses affect neurocircuitry and how particular forms of treatment impact the aberrant responses that occur when someone is ill, we will be more efficient in producing combinations of treatments that are effective and economical. It is very important to keep in mind that we are at the early stage of understanding the meaning of the information gleaned from these scans. As we progress further, more consistent patterns will emerge and guide us to a better understanding of psychopathology and a more consistent and efficient use of available treatments. An exciting set of recent studies by Harner, O’Sullivan, and colleagues (2009) provides clues about the psychological effects of antidepressant administration in acutely depressed versus nondepressed patients. One study (Harner, Goodwin, & Cowen, 2009) has shown that a single dose of antidepressant improves the recognition of positive information about social information (facial recognition) and memory for positive personal characteristics in healthy volunteers. We know the biological changes that occur with antidepressants involve the promotion of synaptic plasticity and learning by an increase in neurotransmitter availability at the synapse. This increase of neurotransmitter availability occurs immediately, but improvement does not. Harner, Goodwin, and Cowen (2009) postulate that the theory of “down regulation” of receptors, second messengers, and gene expression that occurs secondary to antidepressant administration (Frazer & Benmansour, 2002) is less relevant to neurogenesis and change in depression—what actually may occur is the early remediation of negative affective biases. This change could cause patients to interact differently in the world, and the new learning that occurs alters brain structure and function. Harner, Goodwin, and Cowen’s review cites multiple studies indicating that antidepressants alter emotion processing without mood change. A further study published by Harner’s group (Harner, O’Sullivan, et al., 2009) showed that one dose of antidepressant medication normalized three psychological testing measures that are abnormal in depressed patients relative to placebo—including increased recognition of positive facial expressions, more rapid response to positive self-descriptors, and increased memory for positive information. This occurred with no change of mood. If further studies confirm this effect, it could explain the delay in mood change produced by antidepressants and bolster the evidence for the cognitive theory of depression treatment that altering biases in information processing can produce changes in emotion and behavior that eventually reverses depression.

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The data in this chapter generates as many questions as it does answers. We need to be cautious in extrapolating from this preliminary information and be patient as the science develops. A recent set of studies describing a variation on a chromosome looked particularly promising as a risk factor for depression—two copies seemed to convey an independent risk, a single copy increased risk when combined with stressful situations (Gotlib, Joormann, Minor, & Hallmayer, 2008). Unfortunately, with further data, this promising biomarker was found to be not a significant factor (Risch et al., 2009). Ultimately, neuroimaging studies that help us to look at differences between medication and therapy responses of the brain may help us to know how combined treatments could help which particular patients. Particular risk factors could make a patient require both treatments, such as chronic patterns of misattribution that might occur in patients who have Axis II disorders. Over time, we will have particular studies to guide us to use individual or multiple treatments to help patients. Clearly, the neuroimaging findings in anxiety look more clear-cut than in depression—medication and therapy appear to have far more similar actions in anxiety than in depression. This may help us to example the data contained in the disease-specific chapters that follow.

Combining CBT and Medication: An Evidence-Based Approach by Donna M. Sudak Copyright © 2011 John Wiley & Sons, Inc.

CHAPTER

3 Dual Responsibility Treatment Principles That Facilitate Collaborative Patient Care

T

he purpose of this chapter is to describe common problems that can occur when two providers are delivering treatment and to provide a road map for the provision of quality care by integrating a CBT approach both in therapy sessions and pharmacologic management. Multiple books, articles, and reviews exist that detail the possibilities and perils of split treatment, a term used to describe psychiatric care where more than one provider is responsible for the treatment of the psychiatric illness (Dowd & Janicak, 2009; Gabbard & Kaye; 2001, Riba & Balon, 1999). Although the earliest publications refer to care provided by a psychiatrist who prescribes medication and a nonpsychiatrist therapist who provides psychotherapy, today the more common version is that of a primary care physician prescriber and a nonpsychiatrist therapist. Gabbard (2006) has written a substantial amount about split treatment. He succinctly describes the process of communication between care providers. He recommends that as a first step it is necessary to make certain that the patient is aware of and gives informed consent to open communication between the two care providers. This is important to maintain the patient’s trust. This open communication between all parties is also essential to the process of integrated treatment. It must be clear to the patient that there are no secrets between providers and that treatment is a cooperative effort in which all providers act in the best interest of the patient. Gabbard details particular times that require direct communication between care providers. These include emergencies, any substantial change 19

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Dual Responsibility Treatment

in the plan for therapy, and termination of treatment (or contemplation of termination). It might be preferable to label split treatment as dual responsibility treatment or collaborative treatment, as it is called by Riba and Balon (1999). These alternative terms describe more accurately the mutual and collaborative team approach that embodies the best form of care. CBT practitioners are accustomed to developing a therapeutic alliance with patients that emphasizes a shared responsibility for the tasks of therapy and sets goals to actively solve problems and relieve the patient’s symptoms. This therapeutic stance makes it easier to incorporate a relationship with another care provider who has the same treatment goals. Dual responsibility treatment is a reality for many patients, because of access to qualified practitioners, insurance requirements, or prescriptions provided by a primary care physician prior to a referral for therapy. Therefore, it is critical for care providers to have a clear understanding of ways to avoid the difficulties that can arise when two people care for one patient and to enhance treatment wherever possible with integration.

ESTABLISHING A COLLABORATIVE RELATIONSHIP Ideally, communication between colleagues should occur before patients enter the picture—as a practitioner establishes a practice, he or she should begin to look for responsible and compatible co-providers to whom he or she can refer patients for medication or therapy. Time spent seeking out such referral sources, interviewing them, and sharing patient-care philosophies saves enormous effort later. The moment to find a referral source is not when a suicidal and depressed patient is in your office needing urgent intervention. It is a great advantage to have taken a colleague to lunch and established a relationship, so that when an urgent patient referral is needed, you can confidently inform the patient about the provider you would recommend and can communicate how he or she practices. That information paves the way for the patient to see the referral in the most positive light, and therefore he may be more enthusiastic and interested in participating. If you are in private practice, you likely approached the “business” of setting up a practice by consulting a number of professionals—attorneys, accountants, insurers, and so forth—to make your professional life run smoothly. Finding excellent referral sources for your patients is a similarly important process.

Establishing a Collaborative Relationship

21

When you are new to a community, it helps to network with other colleagues to ask about their experiences with other professionals and their recommendations for referral sources. State professional organizations often can provide listings of practitioners (District Branches of the American Psychiatric Association); other specialty organizations (e.g., the Academy of Cognitive Therapy, www .academyofct.org; the Association of Behavioral and Cognitive Therapy, www.abct.org) can give you access to geographical listings to find qualified and trained providers of therapy who have special credentials. If you are fortunate enough to work within an academic center, supervising residents and psychology interns can facilitate your meeting young practitioners who are establishing new private practices. These new graduates will sometimes be practitioners whose work you know from direct experience, and you will also know the quality of their training. In other settings, like community mental health centers, a group of practitioners may work closely with one another to provide patient care. In this circumstance, referrals may occur according to agency policy. Such an arrangement should not replace the same professional collaboration that makes for optimal care. A team approach to patients can occur more easily when practitioners share treatment philosophies and work together frequently. When care occurs in the same setting, peer supervision and case conference groups may exist that enable information exchange and collaborative generation of the formulation and treatment plan. Table 3.1 lists important issues to discuss with the concurrent care provider when initiating collaborative care. These issues will be amplified in the text that follows.

Table 3.1 What to Discuss When Initiating Collaborative Care 1. Philosophy of patient care and explanatory models for psychiatric disorders 2. Prior training and experience 3. Typical frequency of patient contact 4. Cost of treatment 5. Provision of hospital care 6. Coverage during absences 7. Communication between providers and with the patient 8. Preferred methods to make contact in emergencies 9. Preferred methods to manage patient care emergencies (e.g., suicidal ideation or behavior)

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Dual Responsibility Treatment

Philosophy of Patient Care and Explanatory Models for Psychiatric Disorders Two critical items in managing dual responsibility treatment are communication and respect. A good way to begin to develop a respectful relationship is to learn about the model for patient care practiced by your co-provider. Once one determines possible referral sources, the next step is to set up a face-toface meeting or telephone consultation to discuss the possibility of working together. The purpose of this conversation is to understand each other’s philosophy of treatment and the particulars of service delivery within each practice. One must know if the other provider has a radically different model for what helps patients recover. This information is vital to the decision to share responsibility for patients. On occasion, practitioners employ methods that are unorthodox, with no clear evidence about efficacy, and that might be contraindicated based on current accepted standards of care (i.e., using highly emotion-generating forms of therapy with psychotic patients, or routinely prescribing unorthodox off-label drugs for patients). It is also possible that your counterpart has ideas about having personal relationships with patients that are unacceptable to you. Practitioners can also engage in unorthodox methods of receiving payment (e.g., bartering) that are not in accord with your values or the ethical standards of your profession, which would make the relationship a “bad fit.” These are important issues to investigate when establishing this relationship. The initial introductory conversation is also a good time to discuss particular biases about patient care and management. For example, therapists may encounter physicians who know very little about cognitive behavioral therapy and who make comments to patients that can interfere with the treatment provided (i.e., “This ‘thinking positive’ stuff is just treating the symptoms of the problem—it’s not getting to the real cause”). Medication providers can also encounter therapist attitudes that are problematic (i.e., “Of course he changed your medicine, that’s what happens when doctors don’t know what else to do”). These are differences that must be resolved to provide consistent and reliable direction to the patient. Openness to other points of view and dedication to providing the best care possible are optimal traits in your counterpart. Without a meeting to discuss these basics, you may make incorrect assumptions—for example, that the person with whom you are working knows how to make a diagnosis, provide a particular type of therapy, or employ specific medications—that are not true.

Establishing a Collaborative Relationship

23

Prior Training and Experience A matter-of-fact discussion of training and experience is a good way to start to learn about someone with whom you will share patient care responsibilities. I routinely volunteer this information about myself as a way to set an open tone for the conversation. Part of my agenda is to determine whether I am comfortable with sharing responsibility for patients with this provider. In some states, therapists can be licensed by obtaining a business license alone and have little formal training in standard treatments. I need to be respectful, but to ask if the individual is credentialed and by which bodies. Irrespective of the question of which person holds the ultimate legal responsibility when sharing responsibility for a patient, providers assume a substantial risk in caring for a patient who is being treated with treatments that are not known to work or by someone who is not properly trained to help them. If you do not respect or trust the interventions made by your counterpart, therapy will likely fail. Respect must develop in the relationship over time, as two care providers develop a mutual understanding of each other’s strengths, expertise, and clinical acumen. Finally, the way your potential counterpart behaves toward you is a good indication of how he or she conducts relationships with patients. Personal qualities such as warmth, responsibility, and humor can be ascertained in a brief meeting. If I would refer personal friends to the other provider, I know it’s a good fit.

Typical Frequency of Patient Contact After you discuss philosophy of care, training, and experience with your colleague and determine that this relationship is one that will likely work well, a next step is to walk through the experience of a patient who is referred to her. These practical concerns are important to discuss with the patient. How many evaluation sessions will occur? How frequently are patients generally seen after the initial evaluation sessions and how long are the sessions? How long is a patient generally treated for a particular problem? What is the typical time elapsed between a patient’s phone call and the initial visit? A particular item to stress to the patient at the time of referral is that each provider will need to do an independent evaluation and explain the rationale for this procedure. Often the need to be reevaluated is seen as a duplication of effort and a waste of time and money by the patient. In reality, two evaluations are necessary and important—each provider has a different lens through which

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he or she will filter information. Better treatment results when each provider learns the history directly from the patient. To avoid misunderstandings, patients should also be informed that just because they have a medication evaluation it does not necessarily mean they will be provided medication.

Cost of Treatment Although the actual cost of a session may or may not be something you discuss with your colleague—some clinicians prefer to have the patient do so directly—there are important aspects of how financial issues are managed that your patient may wish to know. How are billing and insurance handled? Does the provider accept insurance? Does he or she belong to any managed care panels? Is there a sliding scale available?

Provision of Hospital Care When you and a colleague are sharing responsibility for a patient who has a severe mental illness, the possibility exists that the patient may require hospitalization at some time during your work together. Not every psychiatrist has hospital privileges, and not every psychiatrist admits patients to a hospital as a part of his or her practice. In many communities, psychiatrists refer patients to “hospitalists” or to university settings for care. It is important to know how your co-provider handles this and to discuss this in advance with patients who are likely to require hospitalization.

Coverage During Absences You and your patient need to know how your co-provider arranges to cover his or her practice during vacations and other absences. A frequent problem in dual responsibility treatment occurs when one party makes the assumption that the other will provide coverage to their mutual patients when they are away from the office. This lack of clarity is not just a potential source of resentment. Without an explicit agreement, this assumption can be dangerous—at times, the other provider is not qualified to provide such coverage. In addition, if proper “sign-outs” do not occur, the covering practitioner may not have critical information about the patient in an emergency.

Communication Between Providers and With the Patient Dual responsibility care providers must agree to a method of communication— both when (i.e., weekly, at the time of evaluation and at any significant

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change, monthly) and by what means (i.e., phone, phone message, secure electronic mail). Such communication should occur regularly even when the patient is stable. Naturally, communication frequency should change in response to the acuity of the patient. Identifying the method that the other practitioner uses to communicate with patients between sessions or outside of sessions is also important. One of the most frequent complaints that patients have is that practitioners they phone do not return calls in a timely way. It helps to know how your counterpart does this. Clinicians who leave messages on patient voice or electronic mail without permission can upset the patient and inadvertently breach confidentiality. A great rule of thumb when you are discussing these issues is to put yourself in the position of the patient who will be referred and determine what the experience will be like to be cared for by your counterpart. The following example is a written communication between providers caring for a bipolar patient.

Example of Written Communication Between Providers Dear Dr. Green: I saw Carol this morning. She has implemented the behavioral plan you suggested regarding her sleep habits. Right now she is using the zolpidem about twice a week. She has been far less irritable and sees a positive difference in her impulsivity. Keep me posted if her zolpidem use increases or her spending habits change. I’ll see her in four weeks.

Preferred Methods to Make Contact in Emergencies Communication is critical during patient care emergencies. It is of substantial importance for you to have a reliable means to contact any provider with whom you are sharing patient care responsibilities in an emergency. It also is important for treatment providers to update any changes in contact information with one another. Many providers have a preference about how they wish to receive emergency calls. Identify this during your initial meeting.

Preferred Methods to Manage Patient Care Emergencies One of the most difficult issues that can arise in dual responsibility treatment is when an urgent clinical situation occurs and the two providers disagree about what should be done for the patient. Clinical differences are difficult enough to handle when there is not an emergency—for example, if the medication

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provider thinks a benzodiazepine is warranted for anxiety and the psychotherapist disagrees. When a patient is suicidal or psychotic and there is a disagreement about proper patient management, the problem is greatly magnified. It helps to see this coming. Certain forms of CBT (DBT, for example) have specific protocols for handling suicidal behavior that can be at odds with the usual way that the medication provider manages the situation (see Chapter 10). It is enormously beneficial to discuss these issues at the start of any treatment collaborating. When differences occur in an urgent clinical situation, use all your clinical skills to deliberately and mindfully state the problem as you see it, and ask your co-provider to do the same. Respectfully consider what has been said. If there does not seem to be a “middle path” where you can agree, consider obtaining a consultation from another provider. Finally, take a conservative approach that is most likely to protect the patient when there are disagreements that cannot be immediately resolved.

ADVANTAGES OF DUAL RESPONSIBILITY TREATMENT A patient for whom I was providing pharmacotherapy in collaborative treatment once said, “Now I know what it’s like to have two consistent parents.” Despite the complexity involved in treatment with two providers, there are some real advantages to the approach; when patients are provided truly integrated treatment, they can have a reinforced understanding of the therapy they are being provided and a framework to reinforce medication adherence in both venues. Dual responsibility treatment provides a “wider net” of support for the patient. Vacation coverage for an absent therapist can be provided by a pharmacotherapist who also has skills as a psychotherapist, and who is known and trusted by the patient. In extremely complex patients, this can be quite useful, particularly when the therapist’s absence could cause destabilization or if the patient has a crisis while the therapist is away. An advantage for a prescriber who will not be providing psychotherapy is that when a therapist provides concurrent care, the therapist will see the patient more frequently and can encourage the patient to report side effects and information about the effectiveness of medication over time. Another advantage of two care providers is in clinic settings when therapists or residents and trainees frequently change assignments and therefore have relatively short-term relationships with patients. A consistent care

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relationship with another treating party can provide a sense of continuity and safety that is invaluable to a patient whose treatment is periodically interrupted. Patients in such clinical settings are often afflicted with more severe and chronic illnesses, so the support of a continuous and trusted caretaker can be vital to help them maintain a sense of attachment to treatment when such administrative disruptions occur. This continuous relationship can also provide a safe haven in which to discuss their reactions to such a disruption of care.

MODELS FOR DUAL RESPONSIBILITY TREATMENT Jesse Wright and colleagues (2006) have described a model to conceptualize patients that serves as a blueprint for collaborative treatment with CBT and medications. This approach is also valuable to a psychiatrist who provides both medication and psychotherapy treatment simultaneously. One set of assumptions in this model is the basic assumption of the cognitive-behavioral model of emotional disorders—that is, that psychological disturbances are characterized by disturbances in thinking, encompassing the influence of patient beliefs, thoughts, attitudes, and information-processing style. Behavioral disturbances, including maladaptive coping strategies, also influence learning and cognition. Such disturbances in thinking influence CNS processes. The model goes further to elaborate the biological influences that can operate on CNS processes (like genetics, drugs, and illnesses). It also considers the effects that interpersonal and sociocultural processes have on the patient’s development and current circumstances. This model for patient formulation takes into account a wide range of influences on symptom development and additionally on potential avenues for treatment. When this model is shared by two clinicians who cooperate in the care of the patient, it is an extremely valuable conceptual tool to see how the integration of pharmacologic and psychotherapeutic approaches can benefit the patient. When both clinicians agree about what works to help patients, they can avoid many of the significant pitfalls of split treatment. Psychiatrists who are employing both CBT and medications in the same patient can integrate aspects of medication treatment into the session as a part of the agenda. The amount of time spent focusing on pharmacological management varies depending on the patient, the stage of treatment, and the stability of the patient’s medication. When patients are starting, changing,

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or stopping medication, psychoeducation and symptom monitoring will be a more substantial part of the agenda. Medical problems that patients develop, in addition to their psychiatric disorder, can require changes in dosage or type of medication and become part of the session agenda. Flexible use of the agenda can allow this to occur easily. Integrating treatment with medication and therapy in a dual responsibility model allows each provider the opportunity to present a shared rationale about the benefits of treatment to the patient. Each provider can reinforce the work of the other. Therapists can provide prescribers with typical handouts they use in psychotherapy sessions (like activity schedules or thought records) so that the prescriber is familiar with the particular tools and assignments the patient will employ. Ideally, the prescribing physician will inquire as to therapy attendance, homework compliance, and the patient’s use of therapy skills outside the session. The prescribing physician can provide the therapist with handouts about the most commonly prescribed medications as well as information about typical side effects and how to manage these. Nonmedical therapists with a better knowledge base about the most frequently used medications for common psychiatric conditions are better able to provide education to the patient about medication issues, reinforce adherence, and better facilitate the patient’s communication with the prescriber. The structure of CBT sessions is ideal for “med-check” visits, and, if employed by the prescriber, these checks can further reinforce the model for psychotherapy treatment. Agenda setting, obtaining patient feedback, employing psychoeducation, and further reinforcing what is learned in session with out-of-session activities are techniques that can be useful in medication management as well as therapy. Respect for the collaborating provider manifests itself when you ask the patient well-informed and genuinely interested questions about the other aspects of his care. The tools used in CBT sessions to self-observe are also useful to track medication effects and side effects. When Carol, a patient with bipolar disorder, was concerned about the side effects of valproic acid, her newest mood stabilizer, the psychiatrist working with her had her employ an activity schedule to record any instance of side effects as well as to monitor positive changes she had in her mood state. The activity schedule was a format that her therapist had taught her to use during episodes of depression, and it gave Carol an accurate perspective about the beneficial and negative effects of the new drug. See Table 3.2.

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Table 3.2 Carol’s Drug Side Effect Record (Mornings) Mon.

Tues.

Wed.

Thurs.

Fri.

Satur.

Metallic taste in my mouth

Really feel more steady and evenkeeled

Time 7–8

Had a great night’s sleep, really happy

Slight nausea, okay after breakfast

Sun.

8–9

Concen- 9–10 trated really well in class Lightheaded

10–11 Felt shaky inside

11–12

Better after lunch

12–1

INTEGRATED TREATMENT SOLVES MANY PROBLEMS THAT CAN OCCUR BETWEEN TWO CARE PROVIDERS Treatment that is truly integrated can avoid the frequent pitfalls of having two providers. An example of one such problem is when patients who are in CBT for anxiety are quickly prescribed medication by a psychiatrist or primary care provider before they have had the opportunity to use the tools of CBT. The process of therapy may take days or weeks to produce recovery from symptoms, and at times a brief exacerbation of symptoms (e.g., such as during exposure treatment) is known to be a part of the process. If a patient describes a period of increased symptoms and care providers do not

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communicate, or if one of them does not understand the rationale for such treatment, medication can be used prematurely. When treatment is integrated, this problem can be avoided. The prescriber will understand something about the nature of the intervention; can ask the patient what work he is doing with the therapist to combat the symptom exacerbation; and can inquire as to what homework has been assigned and accomplished. Direct discussion with the therapist can rectify any misunderstandings. Both the therapist and prescriber need to discuss the length of time that therapy will be the “first line” treatment for symptoms and mutually agree, in collaboration with the patient, about what sequence of treatments makes sense. Conceptualizing the patient’s problems together and carefully assessing the degree of disability a particular symptom is causing leads to the formation of a logical treatment plan. Mutual respect and time to communicate are necessary ingredients here—in many types of patients, there will be no “right” answer, and clinical judgment and good communication help the team strike a flexible balance of the use of CBT and medication that is tailored to the needs of the patient. Patients with bipolar disorder, schizophrenia, and severe major depression often require frequent communication between care providers when symptoms become more severe. More aggressive management with increased patient assessment and support can help prevent adverse events. Joint discussions facilitate decisions about what level of care is appropriate for the patient. Symptoms that represent an exacerbation of the illness can be managed aggressively by both practitioners. The following description is an example of collaborative care that illustrates a team approach to symptom reduction. Carol is a 45-year-old woman with rapid cycling bipolar disorder. She has had multiple hospitalizations and severe problems with mania, although in the past five years she has been relatively stable on a combination of mood stabilizers and anti-anxiety medication. Carol also had a history of developing hypomania when she did not sleep sufficient amounts—nine hours or so—at night. Unfortunately, she managed her sleep quite poorly—she often would get quite excited about the movie she was watching or the book she was reading and stay up late, which made her schedule erratic and often provoked symptoms of mania. Carol’s therapist and psychiatrist jointly emphasized the need for her to keep regular sleep hours. They collaborated and discussed with Carol a plan to have her keep a sleep log and work in therapy to develop a better bedtime routine—starting to “wind down” at

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10:00 p.m., and lights out by 11:00 p.m. Carol also agreed that she would take zolpidem if the behavioral plan was unsuccessful in inducing sleep by midnight. Over a period of months, by working diligently with both care providers, Carol was able to take zolpidem once or twice a month and get to bed at a reasonable time most nights.

PROBLEMS IN DUAL RESPONSIBILITY TREATMENT A frequent problem in dual responsibility treatment is when the reason for referral is not clear. Referrals to another practitioner can be for many reasons— to clarify diagnostic concerns, to obtain a second opinion, to obtain a consultation about the treatment plan, or to provide needed assistance with a particularly difficult clinical situation. Make sure that the referral source and the patient are clear about the purpose of the referral. Another problematic situation is when the patient in collaborative treatment criticizes the other provider in a session with you. A critical first step to approach this circumstance is to listen. Nonjudgmentally obtain information about the patient’s concerns. The patient may be describing a situation with complete accuracy, may be describing his own reactions about an event that occurred between him and the other provider, or may be struggling with his own difficulties with interpersonal patterns that interfere with his relationship with the other provider. The next task is to evaluate the patient’s communication and decide what action is needed. This is a situation where your knowledge about your co-provider and his values, practice patterns, and treatment philosophy is of key importance. For example, a prescriber who knows nothing about DBT may react negatively if the patient informs her about a therapist, “And she said if I try and kill myself she won’t talk to me!” It helps to convey interest in the situation, and then approach it as a problem to be solved—both by having the patient make efforts to clarify misunderstandings and therapeutic impasses, and by obtaining more information about your co-provider’s perception of the situation. There are rare circumstances where the other provider is caring for the patient in a way that you believe is unethical or dangerous. When this occurs, several steps are critical. Above all, you must make the best recommendation to the patient about her care. Obtain consultation when indicated—particularly from your malpractice carrier and your attorney. If you recommend that the patient terminate with the other therapist, you must have alternatives available

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and you must respond to the situation with appropriate empathy and concern. If you made the referral to the other provider for the patient, you also need to repair your relationship with the patient. There will also be times when you do not agree with your co-provider. A frank, respectful, and open discussion is indicated here. Be as interested in understanding the other person’s point of view as you are in defending your own. Work to understand the source of the disagreement and seek to mutually agree to a plan for what will best treat the patient. Unarticulated disagreements can pose significant impediments to patient progress and can destroy the relationship you have with your counterpart. These disagreements are particularly toxic when the patient is severely ill and anxiety about the patient is high. If disagreements persist and negative comments are made to the patient about the other treatment provider, it can be highly destructive and detrimental to the patient’s recovery. Patients can have beliefs about having two providers that can cause problems in dual responsibility treatment. A good way to troubleshoot this is to ascertain how a patient thinks about being referred for additional care and what experiences or concerns she has about being cared for by two practitioners. A nonmedical therapist referring a patient for medication should explore thoughts about the referral that could potentially be a problem for the transfer of care. For example, the patient could have beliefs or thoughts about the referral that could interfere with adherence to medication provided, or derail further engagement in psychotherapy (e.g., “My therapist has given up on me”; “This therapy is not working”; “I am a failure”; “Now that I am taking medication, it should solve all my problems”). Patients can also have difficulties because of particular beliefs they have about psychotropic medication, physicians, or psychiatrists (e.g., “Anyone who sees a psychiatrist is crazy”); if these ideas are not elicited and examined, the referral may be compromised. Clearly communicating the rationale for referral and eliciting patient feedback can avoid a number of initial pitfalls and poor connection to the other provider. It is unquestionably the responsibility of the referring therapist to inform and evaluate the thought process of the patient in order to facilitate adherence to the referral and treatment plan. Timing of the referral can influence these thoughts as well. Even when patients are working with a single practitioner, the decision to add or discontinue one form of treatment can have meaning to the patient that influences the therapeutic alliance, adherence, and outcome. For example,

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the therapeutic alliance can benefit when the patient obtains rapid symptom relief with pharmacotherapy. The essence of good care is attending to the patient as a person. Combining treatment may occur after a period of psychotherapy that helps the patient sufficiently evaluate thoughts about medication to make it an acceptable alternative. Therapy can be added as a second modality after a patient becomes more stable and able to think more clearly. Both methods can be used at the start of treatment. Therapy can be added after the patient tapers medication in sequenced treatment. The patient must be informed of the rationale for these pathways to recovery for the best results. Patients can also have problems with interpersonal relationships that make for challenges in dual responsibility treatment. Some patients have such difficulty forming a trusting relationship that having two care providers is not possible. Benign interpersonal interactions are consistently misinterpreted by some patients with Axis II disorders, and these misinterpretations can lead to misunderstandings between providers. These patients can engage in negative interactions with one provider and expect rescue from the other. Although we do not have a good database about what patients cannot tolerate dual responsibility treatment, it stands to reason that highly paranoid or disorganized patients could find it too stressful to develop a relationship with more than one provider. Nonmedical therapists must have a working knowledge of the actions, indications, and side effects of medication to avoid providing misinformation to patients and to assess possible reasons for poor response to treatment. The most likely prescriber will be a primary care physician, since they are responsible for the greatest number of prescriptions of psychotropic medication in the United States (Mark, Levit, & Buck, 2009). Communicating with nonpsychiatrist prescribers can be a challenge because of the substantial time constraints in primary care practices. It is vital that therapists in such dual responsibility arrangements be well informed about medications and particularly encourage patients to report side effects. If nonresponse or partial response to medication treatment exists, psychiatric consultation can be helpful, even if continued management of the patient’s medication will remain in the primary care practice. The following case example of Gene, a patient with depression, is a good illustration of the problems that can occur when therapists are less well informed. Gene, a divorced man with two children, whose ex-wife has primary custody, had been in therapy for depression. He had been prescribed sertraline

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by his primary care physician. He had been doing extremely well in therapy and no longer had sleep problems and suicidal thinking—problems that had plagued him for many months. Just after Christmas, and the return of his children to their mother’s home, Gene developed severe symptoms again. His therapist, Dr. White, was very concerned about them. She determined that he had stopped his medication about three weeks before and had not told his physician. Dr. White told Gene she was certain he was having drug withdrawal and that this was the reason for his symptoms. Gene was really alarmed. He did not want to be “addicted” to antidepressants. When, at Dr. White’s request, he went back to see his primary care physician, he was very reluctant to consider restarting medication, and was unconvinced that his symptoms actually represented a return of his depression. This illustration vividly shows how misinformation can be an impediment to a patient’s medication adherence. Similar problems can occur when prescribers disparage the efforts of therapists or communicate ideas that undermine the therapy (e.g., “you really need to respond to the medication you are taking in order to benefit from any talk therapy”). Not communicating such concerns directly to your counterpart can derail treatment efforts, as the following case example indicates. Irene, struggling with symptoms of panic disorder, went to see the psychiatrist who had been recommended by her outpatient therapist. He was inquiring about the way therapy was addressing her symptoms. When Irene described the interoceptive exposure that her therapist recommended to her, he was shocked. The psychiatrist said he had never heard of such an intervention and that he was concerned that someone would consider performing such treatment. Irene was understandably upset about this. She was able to complete some exposure to feared situations outside her therapist’s office, but dropped out of therapy before starting interoceptive treatment for the panic attacks. A cardinal rule in working in dual responsibility treatment is to maintain an attitude of respect toward the other practitioner, and an open-minded approach to learning new techniques and methods that are grounded in evidence. Such relationships can foster professional growth and be highly beneficial to patient care.

Combining CBT and Medication: An Evidence-Based Approach by Donna M. Sudak Copyright © 2011 John Wiley & Sons, Inc.

CHAPTER

4 Combining CBT Interventions and Medication to Enhance Medication Adherence

W

e can underestimate the anxiety and confusion that occurs in conjunction with being informed that one has a new diagnosis, particularly a psychiatric diagnosis. There is a significant shift in self-perception when one goes from “well” to “ill.” The ramifications of having a severe mental disorder are substantial. Anxiety about future events (marriage, employment, and childbearing; obtaining medical insurance) gradually unfolds as patients begin to think about what having such an illness might mean in terms of the future. As care providers, we must understand the particular personal meanings patients assign to a diagnosis if we are to facilitate adherence to medication and therapy. Best practices in mental and physical health care should help patients achieve the goal of incorporating the concept of being a well person who has a particular illness. The ideal endpoint is to help patients not just be “good patients,” but to live the best life possible with a particular disorder. As a therapist or prescriber or both, an empathic understanding of the patient’s perspective begins by normalizing the patient’s initial questions and concerns about a diagnosis or a particular medication. Treatment adherence is facilitated by understanding the meaning the diagnosis and treatment holds for the patient. This chapter is designed to look at the powerful tools that CBT provides us in combination with medication to facilitate adherence. The principles in this chapter can be used in single or dual responsibility treatment. How much of a problem is nonadherence to medication? Most experienced clinicians do not need a summary of the data to convince them of 35

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the widespread nature of this problem. A recent study indicated that 50 to 83% of patients either discontinue antidepressant medications prematurely or take them inconsistently (Aikens, Nease, & Klinkman, 2008). In primary care, one study showed that approximately 40% of patients never fill a second prescription for antidepressants (Simon, 1992). Up to 50% of patients on lithium prophylaxis for bipolar disorder do not take medication consistently (Scott & Pope, 2002). Patients with schizophrenia have a substantial well-documented rate of nonadherence (Lecompte & Pelc, 1996). Because nonadherence is so widespread we can improve outcomes by systematically targeting it in all of the patients we see who are provided psychotropic medication.

EVIDENCE SUPPORTING COMBINING CBT WITH MEDICATION TO ENHANCE ADHERENCE A number of studies exist that indicate that CBT employed to enhance medication adherence is highly effective in both medical and psychiatric illness. In addition to the studies highlighted in the subsequent chapters, the following is a brief summary of the use of CBT for adherence in bipolar disorder and schizophrenia, two illnesses well-known to have high rates of nonadherence.

Bipolar Disorder Bipolar patients have considerable difficulty with adherence to treatment, often with devastating results. Patients who do not take medication as directed are at risk for manic or depressive episodes. These episodes have inherent physical risks (as a result of reckless behavior and the risk of suicide) and disastrous psychosocial consequences (i.e., bankruptcy, job loss, and relationship disruption). Patients who are nonadherent also incur a greater risk for inducing rapid cycling, a much more malignant form of the disease. Consequently, adherence is even more crucial. Cochran (1984) combined a brief (ten-week) CBT-based compliance intervention with medication treatment for bipolar patients. Patients who received the intervention were significantly more likely to take medication correctly. These patients had fewer instances of discontinuing lithium against medical advice, fewer rehospitalizations, and fewer illness episodes compared to patients with standard clinical management.

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All of the psychotherapies found to be effective adjunctive treatment for bipolar disorder have a substantial focus on psychoeducation and adherence, including CBT for bipolar disorder. CBT for bipolar disorder has a clear benefit in enhanced adherence and decreased relapse and rehospitalization, as reviewed by Lam and colleagues (Lam, Burbeck, Wright, & Pilling, 2009).

Schizophrenia Adherence in schizophrenia is critically important for the health and safety of the patient. Psychotic symptoms are devastating for the patient and his or her family. These symptoms can have life-threatening consequences. Many patients with psychosis have distorted ideas about the causes of their symptoms and the need for medication. They may believe, for example, that their symptoms are caused by the devil or by aliens. CBT interventions have proven to be extremely effective in helping patients with schizophrenia to achieve improved outcomes because of enhanced adherence. Perris and Skagerlind (1994) were able to obtain improved adherence using CBT with patients who were in group homes. Lecompte (1995), both alone and with colleagues (Lecompte & Pelc, 1996), found that schizophrenic patients who had concurrent CBT sessions to promote adherence had significantly fewer hospitalizations. Kemp and colleagues (Kemp, Hayward, Applewhaite, Everitt, & David, 1996) did a randomized controlled trial of a brief (four to six sessions) adherencebased CBT intervention in inpatients. A follow-up of 74 of these treated patients two years after the intervention (Kemp, Kirov, Everitt, Hayward, & David, 1998) found that the treated patients had significantly better adherence, better global social function, and decreased hospitalizations compared to their nontreated counterparts.

CONCEPTUALIZING DIFFICULTIES WITH ADHERENCE Because of the significant rates of nonadherence in many psychiatric disorders— and other chronic illnesses, for that matter—it helps patients when their caregivers assume that taking medication will be a challenge. If we conceptualize a given patient’s difficulty with taking medication, we can better manage the complexity of the issues that underlie nonadherence and tailor interventions. A helpful tool to use in predicting problems with adherence is to consider possible obstacles on a DSM IV multiaxial continuum. On Axis I, the

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diagnosis itself can produce problems with adherence—major depression, for example, is characterized by hopelessness, and this hopelessness can extend to and interfere with the patient’s engagement with medication treatment. Co-morbid substance abuse can cause patients to neglect taking medication because the abuse interferes with memory and self-care and can also produce unfavorable drug interactions. Axis II disorders, co-existing with problems that require medication, are characterized by belief systems that make it likely that patients will interpret benign interpersonal interactions and events idiosyncratically and inaccurately. When these belief systems exist about medications or relationships with prescribers, they are likely to produce problems with adherence. Axis III—medical problems—can produce problems with adherence by increasing stress and increasing the complexity of the medication regimen the patient must manage. In addition to using CBT tools for adherence to psychotropic medications, these tools also facilitate patients with chronic medical problems’ adherence to their medication regimens (Sensky, 2004). Axis IV prompts us to consider psychosocial stressors. Any psychosocial difficulty can interfere with adherence—financial problems, lack of adequate social supports (or worse, a social network that jeopardizes adherence), and lack of access to treatment all can be problems. Imagine the impediment that homelessness is to the life-habits that facilitate regular medication use. Lastly, the patient’s current level of global functioning, Axis V, is an indicator of how much external support may be needed to help the patient take medication regularly. Thus, the multidimensional framework provided by DSM IV can help clinicians organize their thinking and troubleshoot adherence problems. Once a patient agrees to take medication, a good method to use to discover obstacles to taking medication is to focus with the patient on what the dayto-day process of taking the pills will be like. Ask a question about how and when the patient will take the medication. A more honest discussion can occur if it is acknowledged that it is difficult for anyone to take medication every day. Self-disclosure can facilitate this, if the clinician is comfortable with doing so. Most of us have had the experience of not following medication regimens exactly as prescribed. Such a disclosure may allow a patient to be honest about his own struggles with regular medication use. Patients are typically embarrassed by not following through with taking medication regularly and will under-report lapses. Once the problem is on the table, collaborate and brainstorm! Taking medication regularly is so important for recovery that a goal of

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treatment must be to work together to help the patient to take medication as accurately as possible. Beck (2001) classifies problems with adherence as either practical, psychological, or a combination of the two. This classification rapidly allows clinicians to hone in with the CBT tools best designed to help with the problem. The initial assessment should consider the day-to-day life of the patient, with an eye toward practical concerns that could pose problems. This is a time to be creative. Put yourself in the patient’s place. Help the patient think through realistic obstacles that could crop up along the way. Psychotropic medication is frequently needed for months, years, or a lifetime. This means that obstacles to adherence often change over time. Discussions about adherence need to be ongoing and updated as the patient’s life changes. For example, a patient’s financial status, insurance coverage, time demands, interpersonal needs, and health status may change—and each of these variables may produce practical concerns that can make taking psychotropic medications more difficult. Women on psychotropic medication may desire to have children, with the need to reevaluate prescriptions and reassess options (see Chapter 11). Good treatment occurs when each provider on the patient’s care team repeatedly targets and problem-solves the issues patient perceives with taking medication, and anticipates and troubleshoots problems that may occur in the future.

TECHNIQUES THAT FACILITATE MEDICATION ADHERENCE Taking medication accurately is difficult even for a short period of time. Think about your own experiences taking medication. Better still, if you have children, think of trying to give them medication as required. It is likely that even when you had the best intentions of following the doctor’s instructions, you did not do it correctly every time. You likely employed behavioral interventions to help you remember to take the medication prescribed. Behavioral interventions can be highly effective tools to use to help patients take medications regularly and correctly. Behavioral interventions of some type are almost always needed to help us form new habits, even when our attitudes and beliefs about medications are positive. The behavioral techniques most commonly used to enhance adherence are provided in Table 4.1, followed by a description of each.

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Combining CBT Interventions and Medication Table 4.1 Techniques That Form Good Medication Habits 1. Self-monitoring 2. Reminder systems 3. Positive reinforcement for taking medication correctly 4. Uncomplicated medication regimens (fewer doses per day, as small a number of pills as possible) 5. Psychoeducation

Self-Monitoring Self-monitoring is a terrific tool to help patients take medications more effectively. A chart that the patient keeps with each dose entered can remind him to take medication and provide a record of how frequently adherence is a problem. An activity schedule, much like those used for behavioral activation for depression, can be used as a recordkeeping device. Patients can enter times when they took their medication and can additionally note the beneficial or troublesome effects it has throughout the day. Selfmonitoring can be paired with reinforcement—after the patient enters a note that he has taken the medication, he can also chart items that he picks from a “menu” and use them to reward a job well done. (See the section on positive reinforcement.) A particular benefit of self-monitoring with a medication record is that it may reinforce the positive benefits of medication to the patient, and therefore he will not disproportionally notice the side effects. Frequently, when we monitor patients on medication, we weight our discussions to identify and solve problems with side effects, without an equal balance of asking them about beneficial effects. This practice is even more frequent after the patient has had an initial symptomatic improvement. Although efficient, it has the unintended consequence of reminding the patient about unwanted effects without reinforcing the benefits. Many patients who take psychotropic medications will need to keep taking them for long periods when they are without symptoms. During these times, it is critical to reinforce the positive value of medication. Another source of reinforcement may occur when clinicians remind patients of the therapeutic effects of medication in session, as this example from Carol, the patient with bipolar disorder we met in Chapter 3, illustrates.

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Clinician: I’d like to check on how your mood has been this week. Carol: Up and down, but nothing abnormal. I’ve had a few setbacks at work that really affected me. Clinician: Should we put work setbacks on the agenda? Carol: Yes. That’s what I’d like to talk about. Clinician: Sounds good. But before we start, let me check on how often you had trouble remembering to take your medication. Carol: I did really well this week. That pill box really helps. Clinician: That’s great. I think the medicine really has helped you to stay on track and to maintain a normal amount of mood change when difficult events happen in your life, but not have things spiral out of control. Carol: I think so, too.

Reminder Systems Reminder systems are another powerful tool to foster good medication habit management. First, it helps to label the adherence to medication as a habit—and to ask patients what has helped them to form good habits in the past. Then you can brainstorm ideas together that would be a good fit for this particular patient. Reminder systems can be low-tech (like a reminder card on the bathroom mirror, or a pillbox marked with the days of the week that the patient refills at a designated time) or high-tech (like setting cell phone or computer-based alarms that remind the patient it is time to take medication). The most important thing to remember about any reminder system is that it will only work if it is used. A pillbox will not be useful if it is never filled, and a three-by-five card will not help anyone if it is kept in a drawer and never read, or if it is taped to the mirror and ignored. Discuss the obstacles to the use of these systems and troubleshoot potential problems in session. One belief that is a frequent barrier patients have to the use of these tools is the idea that they “should not need” to use reminders. Patients often have the idea that since medication is “good for them” that if they “really wanted to get better” they would take it without difficulty. It is easy to forget that we are human. Shame is a frequent barrier to good adherence. Patients are often reluctant to discuss struggles to take medicine because they are concerned that care providers will see them in a negative light. Shame is more prevalent in patients with high standards. Patients who are ashamed of taking psychotropic

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medications in particular will often avoid the use of reminder systems because they do not want other people to know that they are taking the pills. Be creative in working to find a solution that fits the patient’s needs and life circumstances. A wonderful and commonly used variant of reminder systems is to pair medication doses with routine activities. You have likely used this behavioral strategy yourself. It works best when the paired activity is one that occurs daily, at the same time every day, and is not likely to vary when other routines vary—like taking medication when brushing teeth, either in the morning or at bedtime. This is not a good strategy when patients have erratic routines or personal habits.

Positive Reinforcement for Taking Medication Correctly Positive reinforcement helps everyone learn new habits. Unfortunately, many patients will say they “don’t deserve” positive reinforcement for doing something they “should” be doing, like taking medication. It helps to skillfully explain that the goal is to rapidly and successfully get a result that will benefit the patient’s health, and that rewards will work! Patients benefit when they know that it is effective to reward behavior that promotes health and well-being. Several recent studies, for example, have shown that patients lose weight far more successfully with the prospect of tangible cash rewards than if there are no rewards available (Volpp, John, Troxel, Norton, Fassbender, & Loewenstein, 2008). Creatively identify small, tangible behavioral rewards (reading a favorite book for 15 minutes, buying a favorite magazine) and cognitive rewards (mentally praise yourself, e.g., “You are doing a great job managing your illness”) with the patient. Assign the patient the task to employ them each time she takes medication as prescribed.

Uncomplicated Medication Regimens No discussion of behavioral methods that promote adherence should omit the behavior of prescribers. A very obvious thing that prescribers can do to enhance adherence is to prescribe medication with as simple a dosing regimen as possible. The least number of medications in the smallest number of doses works best. Prescribers also need to attend to the therapeutic alliance in a deliberate and careful way, because the quality of the prescriber’s relationship with the patient has a substantial impact on the patient’s adherence.

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Psychoeducation Education is another important component that facilitates good medication habits. One important guideline is to “tailor” the education to the patient as a person; for a prescriber, this is more than providing the reason for the prescription and the risks versus the benefits of a particular treatment. Some patients need more information than others, and for some, the sources they use to obtain information can make adherence more or less likely. The Internet, for example, is both a blessing and a curse as a source of information about health issues. A great way to start is to ask the patients what they know about a particular illness or treatment and the source of their information about medication or the diagnosis (e.g., “What do you know about depression? Has anyone close to you ever taken a medication like this? How do you generally find out about pills you take?”). This line of guided inquiry will allow you to conceptualize and better tailor the information necessary for a particular patient. As you explain the treatment available, continue to get feedback and encourage questions. Remember that the patient’s illness is likely to alter her capacity to learn and remember, so education may need to happen repeatedly and in small doses. Once you have explained the treatments available, the next step is to ask the patient how she wants to proceed. If she refuses medication the task at hand is to ask the patient if she wants more information or more time to make the decision. If the answer is still “no,” cognitive techniques may be indicated (see the later section on examining pros and cons). It is particularly important to provide just the right amount of information about medication side effects. Frequently when prescribers discuss side effects, they do not make clear how infrequently these effects occur. Anxious patients can become hypervigilant for adverse reactions, or can even refuse to take medication if given extensive information about negative outcomes. It is helpful to frame side effects as a result of medication having “effects we want and effects we don’t want” and to indicate that the balance with useful medicines is far tilted toward the beneficial effects. Any discussion of medication treatment must be accompanied by written information and by instructions to the patient to take notes and to write down questions between sessions. Genuine interest in the patient’s point of view and feedback about the patient’s experience enhance all aspects of the therapeutic alliance and reinforce the idea that the therapist, prescriber, and patient are a team. Written information and repeated instruction are extremely important,

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because anxiety, depression, and psychosis influence the capacity to learn and remember. Patients who think that their care team will seriously consider their concerns and work with them to resolve problems will more likely take medication as prescribed.

TECHNIQUES TO USE WHEN MEDICATION ADHERENCE IS A PROBLEM Cognitive and behavioral techniques can be useful when problems arise in medication management. Careful behavioral analysis can uncover the “sticking points” that interfere with the habit of taking medication. Behavioral experiments can help patients test dysfunctional assumptions about medicines. Cognitive techniques are generally most helpful when beliefs, attitudes, and thoughts the patient has are the impediments to adherence. These maladaptive ideas are very common causes of nonadherence. One study has shown that the patient’s beliefs about medication and the etiology of his depression are key reasons for lack of adherence to antidepressant treatment (Aikens et al., 2008). Beck (2001) classifies categories of interfering cognitions as thoughts about the self, thoughts about medication, thoughts about physicians or psychiatrists, and thoughts about mental illness. A list of techniques that can be helpful to patients who have problems with adherence can be found in Table 4.2. These techniques are familiar to cognitive behavioral therapists. They are described here to illustrate their use in helping patients achieve good medication adherence.

Table 4.2 Techniques to Use When Medication Adherence Is a Problem 1. Behavioral analysis of difficulty with adherence 2. Behavioral experiments to test beliefs about medication 3. Examination of pros and cons of taking medication 4. Evaluation of thoughts that interfere with medication adherence 5. Development of new rules and beliefs about taking medication 6. Problem-solving and anticipatory planning 7. Coping cards 8. Cognitive rehearsal

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Behavioral Analysis of Difficulty With Adherence Behavioral analysis is a potent tool that can be applied to problems patients have with adherence. This familiar technique involves obtaining a detailed description of the thoughts, emotions, and behaviors that occur in the sequence before and after a particular behavior—in this case, nonadherence. This careful, step-by-step look at each of the antecedents and consequences of nonadherence can help the clinician and patient determine targets for intervention. The following case example illustrates this process. Rachel, a 20-year-old college student, struggled to remember to take her antidepressants and had difficulty obtaining consistent symptom relief as a result. She had several episodes of breakthrough symptoms that interfered with her exam performance. Her therapist, Dr. Black, in his weekly check-ins about medication, had identified adherence as a problem. He verified with the psychiatrist at student health that Rachel was on a single bedtime dose of an antidepressant, and that Rachel had responded well when she took the medication regularly. The psychiatrist was seeing Rachel every three months. The therapist introduced the issue of medication adherence during agenda setting, after Rachel informed him that she failed an exam the week before because of problems concentrating and sleeping. Dr. Black: Rachel, I was hoping we could put the problem you’ve been having taking your medicine regularly on the agenda. I know you were really upset about the history exam you failed, and you said it was clear to you that you had done poorly because you had trouble concentrating and sleeping. Rachel: You know, I just blew it. I know that if I don’t take the pills I have trouble. It is just impossible for me to remember. Dr. Black: Maybe we can take a look together at what the times you forget have in common. Would that be okay? Rachel: Sure. Dr. Black: When was the last time you didn’t take your medication? Rachel: I missed Monday and Tuesday this week. I figured it out on Wednesday when I wasn’t sleeping well. Dr. Black: Okay. Since that is the most recent time, let’s go through step by step what happened. I think that would help us. I know you take the pills at bedtime, so let’s start with dinner on Monday. If you were to “play a DVD” of what happened for me from

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Rachel:

Dr. Black: Rachel: Dr. Black:

Rachel:

Dr. Black: Rachel:

Dr. Black:

Rachel: Dr. Black: Rachel:

dinner, what would I see? Can you describe it in that kind of detail? Sure. I had dinner at Charley’s (Charley is Rachel’s boyfriend)— I got there after he was done with work at eight. We had dinner, and then I studied while he cleaned up. It was a really nice night. We decided to watch a movie after I finished my homework. And then it was midnight and I was sleepy so I spent the night. I would have taken the medicine—I thought about it—but I didn’t have it with me and I didn’t want to go home. So I just skipped it. Is this unusual? Gosh, no. I probably have that happen once or twice a week. Wow. That’s pretty often. Being without the pills once or twice a week could really be the cause of lots of breakthrough symptoms. I wonder if you ever thought about some ways to solve the problem. Well, the problem is that I have to take them at bedtime because they make me sleepy. I always get my birth control pills caught up because I can take them anytime of the day so when I get back to my dorm, I just do it. But I can’t do that with the antidepressants. That makes sense. Are there any solutions to this problem that you can see? I don’t know. I know you’ll tell me to keep some at Charley’s place. I did think of that. But Charley doesn’t know I’m taking the antidepressants and I am too embarrassed to tell him. I don’t know what he would say. Well, that dilemma could stop you in your tracks all by itself. Let’s see what we can come up with. It sounds like we could tackle this in two ways—one would be to see if we could figure out a way to make certain you had medicine with you all the time, and another would be to look at the thoughts you had about what Charley would do if he found out about the medication. Which do you think is the bigger problem with taking the pills? Having them there. When he’s at the dorm with me, I just take them. I keep them in an old vitamin bottle and I’m fine with it. Okay. This makes it easier. What can you think of that will allow you to always have medicine available? Duh. Put some in my purse? I mean I can’t believe I hadn’t thought about that.

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Dr. Black: Well, maybe you hadn’t realized what a big problem it was—it’s easy if you think “it’s okay if I forget once in awhile.” But each of these times really adds up. And we need to get really practical about this—what do you carry with you all the time? Rachel: That’s not a problem—I always have my purse with my dorm keys and phone. Dr. Black: So what we need is for you to have a container in that purse and a reminder to fill the container every week. Can you program that into your phone? Rachel: That’s pretty easy. I can do that. And I have a tiny ibuprofen bottle I keep with me that I can use. Dr. Black: Okay. So you’ll put some of your pills in that bottle and have a phone reminder to check the pill bottle once a week. This is a terrific plan. Let’s check into how this works over the next couple of weeks. So can we look at what happened on Tuesday—was it the same problem? Dr. Black and Rachel do another behavioral analysis of Tuesday’s medication issues. They determine that the issue on Tuesday was that Rachel wanted to study until quite late—until four o’clock in the morning—and that she would have been too sleepy if she took the pills. They worked on the pros and cons of staying up versus taking medication, and Rachel agreed to try to employ a cut off of two o’clock in the morning for her bedtime so she could always take her pills. These vignettes illustrate the value of a detailed behavioral analysis when adherence is a chronic problem. Dr. Black was able to identify multiple behavioral and cognitive obstacles to good adherence in this instance, and to employ a variety of cognitive and behavioral strategies in a tailored and efficient way. This vignette also illustrates the substantial value of coordinating care in dual responsibility treatment. It is fairly typical for patients who are taking a stable dose of medication to see the prescriber at intervals of six, twelve, or twentyfour weeks. These infrequent visits make it mandatory for the therapist to evaluate and troubleshoot adherence issues for optimal patient management to occur. One final point about this vignette is that it is always important as a prescriber to think about the person receiving the prescription, and conceptualize particular adherence issues that this person may have. A young college student is likely to have very different issues about adherence than an elderly patient with multiple medical problems.

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Behavioral Experiments to Test Beliefs About Medication Behavioral experiments are another valuable tool that clinicians can use to enhance the likelihood that patients will take medications. This technique can help the patient who is anxious about trying medications for the first time. Generally, these are patients who are very anxious about a side effect occurring that could be dangerous. The following clinical interchange shows the technique in action: Dr. Scott: Alex, it looks like we’ve pinned down your reluctance to starting the antidepressant as stemming from your concern that you could have a bad side effect. Alex: Yes, that’s true. I have just read so much about SSRI antidepressants making people agitated and suicidal. Things have already gotten so bad for me. I’d be worried that if I felt any worse, I would just go into pieces. Dr. Scott: I can see how that thought would really make you reluctant. I had had good results with patients who had these concerns by having them take the pill in my office and then spend as long as they’d like in my waiting room after they take the pill. I’ll be in and out of the waiting room throughout the day so if you had any bad reactions we could handle it together. How do you think that would work? Alex: Well, I think I’d be a lot less anxious. I can do it this Friday because of my schedule. Is that okay? Dr. Scott: Works for me. Another great use of the concept of behavioral experiments is to frame the idea of taking medication as an experiment—something that might or might not be helpful for the patient—and specifying a period of time after which you and the patient would reevaluate symptoms and discuss whether or not to continue the medication with the medication provider (or with you, if the patient is in single-provider treatment). The following example illustrates this type of behavioral experiment in a patient receiving care from two providers. Ms. Green: Jean, it sounds to one like you really think of medications pretty negatively and are not very confident that they will be very helpful.

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Jean: That’s true. I really don’t have much faith in them. I had that one bad experience when I was in my 20s with antidepressants. I almost wound up in the hospital with blood pressure problems. And I really came to the conclusion that no one really understood anything about how these medicines worked. Ms. Green: Well, that experience would stand out in your mind. Have you talked to Dr. Scott yet about medications, as we discussed? Jean: No, I haven’t Ms. Green: You know, we have already done the experiment of how much therapy by itself has been able to help you with your depression. How would you rate that? Jean: I’m still pretty lethargic and although my anxiety and sleep are better, they are not great. And I feel like I have been working pretty hard. Ms. Green: I’d agree with that. I’d say you have made a good effort to do the things we’ve talked about that would help you with your symptoms. Jean: That’s true. Ms. Green: What would you think of trying the combination of CBT and medication as an experiment? If you developed side effects that you really disliked, and if we could not help you handle those, then you could always talk to Dr. Scott and stop the medication in the way she suggests. And if, after eight weeks, you decide the medicine has not helped you, we’ll talk to Dr. Scott about what should happen next. We’ll have you keep an objective record of your symptoms so that we will know for certain what difference, if any, the medicine has made. I don’t want you to feel forced, but I don’t want to miss an opportunity to help more if that’s possible. What do you think? The type of collaborative relationship is typical of CBT in action. The continual search for objective data to evaluate the results of interventions is a paradigm for the type of work that the patient will do in therapy.

Examination of Pros and Cons of Taking Medication If a patient is unwilling to take medication, it helps to develop a list of pros and cons about doing so. Make sure you remain empathic and preserve the therapeutic alliance while exploring these ideas. This process works best when

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the patient looks as widely as possible for benefits and evaluates carefully any perceived negative effects of medication. Remember, any ideas about negative effects on the patient’s list must be supported by evidence. An exploration of these ideas often leads to an understanding of the beliefs interfering with the patient’s adherence—either about medication, illness, or people who take psychotropic medications. The following vignette illustrates this process. Gene, a 46-year-old man with major depression, was very reluctant to take medication despite very severe insomnia and anhedonia. His work performance had deteriorated dramatically. When he discussed his reluctance with Dr. White, his therapist, she asked him to make a list of the pros and cons of taking medication as an activity to do between sessions. Gene returned with just one “con” on his list; “If I take medication, it means I am a weak person”. Identifying this rule allowed them to proceed to evaluate how accurate the rule was, and helped Gene to agree to a trial of antidepressant medication.

Evaluation of Thoughts That Interfere With Medication Adherence Maladaptive thoughts about medication, illness, and physicians are common problems encountered with patients taking psychotropic medications. Prescribers and therapists can inquire about these ideas in the process of referral and assessment. Questions about prior experiences with medication, beliefs about certain types of medication, or experiences of significant others with particular drugs, can be very helpful to elicit ideas that can interfere with a good outcome. Specific thoughts about a particular type of illness or medication can often interfere with adherence. Examples of such thoughts include “antidepressant medicines are addictive” or “taking medicine because you are anxious is just a crutch.” These thoughts are often easily corrected by educating the patient or by having the patient obtain evidence about them. Maladaptive ideas about psychotropic medications are extremely common and highly influenced by family and culture. If you go to an Internet chat room for any particular type of medication, you will discover how extensive and distorted they are! Many illnesses, particularly psychiatric illnesses, have a legacy of cultural stigma. A diagnosis of cancer or tuberculosis was believed to be shameful just decades ago. My grandmother thought cancer was uniformly fatal and that the process of removing the cancer would cause it to spread all over the body. Similar misconceptions exist today about psychiatric illness and psychotropic medications. Correcting these is vital to obtaining good adherence.

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Development of New Rules and Beliefs About Taking Medication Beck (2001) has pointed out that specific beliefs about an illness (as referenced above) are more easily evaluated and changed than more general beliefs about health care providers (such as “Doctors really don’t know what they are doing”) or than specific belief systems patients have about themselves. These more general beliefs may need to be subjected to experiments and evidence gathering, as in the following example. Gina was hypervigilant for adverse effects of medications, because she believed, “If anyone gets a side effect, I will” as a fundamental corollary to her core belief, “Bad things always happen to me.” This thought was the first one that came to her mind when she filled her new antidepressant prescription. She took the first pill with a great deal of trepidation. For several hours, she continued to scan her body for dizziness, heartburn, and palpitations. Needless to say, she was uncomfortable and on edge the whole time. She stopped the pills after one dose. During her next appointment she discussed her “bad experience” with the medication. Her therapist, Dr. Wolfe, asked her about the thoughts that she had about taking the pills and the actual experience she had had after taking the antidepressant. Gina: I just could not relax after I took them—I was pretty certain that I would have a bad reaction. That would be just my luck. Dr. Wolfe: Well, I suppose that is possible that you would be a person who always had bad reactions to medication. But was what happened to you a reaction to the medication or a reaction to how nervous you were about having a bad reaction? Gina: The second one, I guess. Although since I only took the pill once, I never had much chance to get a bad side effect. It still might have happened. Dr. Wolfe: Well, that is possible. But I wonder if we could look together at the idea that you always get bad side effects from medication to see how accurate that is. Gina: I guess we could. Dr. Wolfe and Gina constructed a table listing all the prescribed medications, over-the-counter pills, and vitamins that Gina could remember taking over her lifetime. On the right-hand side of the table, he had Gina fill out any side

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effect she remembered. Except for hives when she took penicillin and nausea when she took codeine, Gina could not recall any significant side effects from the 18 different medications listed. This information helped her to draw a different conclusion about how likely it was that she would have a bad reaction, and she was able to take the antidepressant medications prescribed. Not every cognitive distortion that patients have about medication is negative. Positive, untrue beliefs about medication can also be an impediment to therapy. For example, patients may have beliefs that medication will solve all their problems, or that they will no longer need to make efforts to change problem behaviors if they are on medication. Often these attitudes are reinforced by the pervasive advertising about psychotropic medication, which clearly exploits the most positive ideas about medication use. Patients can have a distorted perspective that medication will “cure” their psychiatric disorder as well, which is seldom the case. Finally, more global beliefs that patients may have about the motives and trustworthiness of others, such as those that occur in Axis II disorders, may need special attention. Ideas like “People can’t be trusted,” “I must always be on guard for people who could harm me,” or “I’ll never be able to take care of myself,” will understandably interfere with medication adherence. Attitudes like this may require a longer-term approach: slowly building a trusting relationship with the patient and accepting the best successive approximations of medication adherence possible.

Problem-Solving and Anticipatory Planning A good example of problem-solving and anticipatory planning is seen in the case of Rachel, described above. Rachel and her therapist determined that she had particular problems taking her medication when she spent the night away from the dorm. She was able to identify the problem, generate solutions, and put a plan into action that had a good likelihood of success. When a patient’s life circumstance changes for any reason, it can affect medication adherence. Troubleshooting challenges to taking medication as directed in a matter-of-fact way can teach the patient to anticipate and problem-solve challenges to taking medication in the real world.

Coping Cards My most talented ski instructor once directed me to write down the two most important things that I had learned after a particularly good lesson. She told

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me to put that card into my ski bag and to take it out and read it before I went out to ski the next time. This is an excellent example of a coping card in action. Coping cards are brief, bullet-point style reminders of significant points learned in therapy sessions. They are designed for the patient to use when he approaches similar situations or trouble spots in the week ahead. Gina and her therapist generated a coping card after the session described above. She was instructed to read it before she took the medication or whenever she felt anxious about taking the medication. When I think that “every bad side effect always happens to me,” I should remind myself: • I have taken 18 different kinds of medication and I only had bad side effects twice. • Dwelling on the possibility of getting a bad side effect won’t make it less likely and will make me feel uncomfortable. • I have taken one dose of the antidepressant and I have been okay.

Cognitive Rehearsal The use of mental practice is a wonderful CBT tool to help discover obstacles to good adherence. Behavioral, cognitive, and interpersonal obstacles to medication adherence are often found when the patient visualizes leaving the office with the prescription, obtaining it, getting home with it, remembering to take the medication (or not), and anticipating the side effects, benefits, and reactions of other people to the medication. This can lead to an active discussion of barriers and solutions, which can then be practiced in the session or as cognitive rehearsal for homework. Integrating CBT treatment strategies with medication management has definite positive effects on adherence to medication. Therapists and prescribers, or prescribers who use both medication and therapy, can proceed with confidence in the substantial evidence that the use of both methods makes a real difference in the patient’s use of medication for depression, schizophrenia, bipolar disorder, and panic disorder. In collaborative treatment, the efforts of both providers promote adherence most effectively when treatment is integrated. Each provider must ask about adherence to the other treatment modality and assign outof-session activities that promote it. These activities reinforce the importance of both forms of treatment and increase the likelihood of success.

Combining CBT and Medication: An Evidence-Based Approach by Donna M. Sudak Copyright © 2011 John Wiley & Sons, Inc.

CHAPTER

5 Combined Treatment for Major Depression OVERVIEW Depression is a major public health problem and a leading cause of disability in the United States, affecting roughly 15 million American adults (Kessler, Chiu, Demler, & Walters, 2004). Patients with depression have higher rates of co-morbid medical illness and suffer from significant interpersonal and psychosocial consequences, which further adversely impact their lives. Suicide is a substantial risk in depressed patients. Depression is highly recurrent and is frequently incompletely treated. STAR*D (Sequenced Treatment Alternatives to Relieve Depression) was a practical clinical trial designed to demonstrate the effectiveness of antidepressant medication in the “real world.” Its results indicated that despite advances in pharmacological treatments for depression, the reality of antidepressant treatment effectiveness is that only one-third of patients with depression remit after a single trial of an SSRI (Warden, Rush, Trivedi, Fava, & Wisniewski, 2007). Furthermore, the likelihood of remission becomes less with each successive medication trial, and a lack of response imparts an increased chance of relapse. Residual symptoms, even in patients who sustain a remission, are a substantial burden for the patient, and play a role in increasing the risk of relapse (Nierenberg et al., 1999). Another significant problem that impacts treatment effectiveness in patients with depression is nonadherence to medication. Nonadherence to antidepressants is extremely common, both in primary care and in psychiatric treatment. In primary care, 40% of patients discontinue medications within 55

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six months, regardless of what antidepressant is prescribed (Simon et al., 1999). This figure is barely better in psychiatric treatment. In the STAR*D study, 28% of patients discontinued initial treatment with citalopram. In this nonadherent group, 92% discontinued medication for nonmedical reasons, 66% within the first week of prescription. Additionally, the more depressed patients were, the greater the risk for attrition (Warden, Trivedi, Wisniewski, et al., 2007). Combined treatment with medication and cognitive behavioral therapy (CBT) may be a more effective option in depression, both increasing the percentage of patients with depression who sustain a remission and decreasing the risk of recurrence. This chapter will present evidence that supports the combination of medication and CBT. It will also discuss particular pitfalls in managing these patients in dual responsibility treatment, including managing suicidal patients, working in dual responsibility treatment when the patient is receiving pharmacotherapy in primary care, enhancing adherence to behavioral activation in dual provider care, and managing the patient with mixed anxiety and depression. One note is that this chapter is an overview of treatment for unipolar depression. The use of CBT in conjunction with medication for bipolar depression is found in Chapter 6.

EVIDENCE FOR COMBINING MEDICATION AND COGNITIVE BEHAVIOR THERAPY IN DEPRESSION Assessing the research on depression is complicated by the difference in inclusion criteria for studies and the duration of treatment provided. An additional problem is that studies vary in the definitions used for relapse and recurrence. Until uniform standards exist in research it will be difficult to precisely compare treatments. Because of this lack of uniformity, it helps to divide the research evidence into evidence for treatment with both medication and CBT in acute depression, in chronic depression, and for recurrent depression (e.g., evaluating the durability of response). Studies reviewed for this chapter are studies of major depression. Dysthymia is another prevalent and difficult-tomanage clinical entity, but was not a part of this review.

Acute Depression In acute depression, that is, in studies of patients where the initial treatment provided for depression is evaluated, CBT is as effective as medication in mild,

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moderate, and severe depression in placebo-controlled trials (Hollon, Jarrett, et al., 2005). This efficacy has been shown in numerous, well-designed studies. Importantly, many studies, particularly earlier trials, do not control for or enumerate the number of prior episodes of depression in their subjects. Many of the early studies that compared CBT, medication alone, and the combination showed small but not statistically significant trends toward the combination being superior (Hollon, DeRubeis, et al., 2005). The robust response rates for each treatment alone made these smaller studies less able to demonstrate a significant difference for the effectiveness of the combination of treatments. To evaluate whether the combination was significantly better, several authors performed statistical analyses, the findings of which indicate that the combination of CBT and medication is a significantly superior treatment for acute depression than treatment with either agent alone. Friedman and colleagues (Friedman, Wright, Jarrett, & Thase, 2006) used the data from 685 patients in 5 studies and concluded that for every 5 patients treated with the combination of antidepressants and CBT, 1 additional patient would respond. Cuijpers and colleagues (Cuijpers, van Straten, Hollon, & Andersson, 2010) evaluated 16 studies with a combined total of 852 patients and determined that the combination of active medication and CBT was superior to the combination of placebo and CBT, with a number needed to treat of 7.14. One large-scale study that indicated a greater effectiveness of a combination of CBT and medication was the Keller et al. (2000) study comparing CBASP, a form of CBT, nefazodone, and the combination of the two. This study enrolled sufficient patients that the statistical power existed to show differences between groups. Furthermore, this study enrolled difficult, chronically depressed patients who were far less likely to be easily responsive to any treatment. Another impressive finding in this study was that patients were found to have characteristic symptoms and/or psychosocial history that predicted a response to one particular treatment versus another. For example, patients who had insomnia were less likely to do well if they were in the group that did not receive medication with psychotherapy, compared to the group that received psychotherapy alone (Thase et al., 2002). Anxiety was another symptom that predicted the need to combine medication with psychotherapy compared to psychotherapy alone (Ninan et al., 2002). Patients with childhood abuse, in contrast, improved more substantially if treatment included psychotherapy (Nemeroff et al., 2003). Fournier and colleagues (2009), in analyzing data from another study that compared CBT with medication in moderately

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to severely depressed outpatients, found that chronic depression, older age, and lower intelligence were predictors of poor outcome in either treatment, and that marriage, unemployment, and recent stressful life events predicted a better response to CBT relative to antidepressants. Thus, there may be particular patient variables to help us recommend the most effective course of action.

Chronic Depression In the 15 to 20% of patients whose depression is chronic, meaning that it has been in existence for greater than 2 years without remission, recovery is far less certain. Combined CBT and medication in these patients may be extremely helpful. Several studies (Keller et al., 2000; Paykel et al., 1999) indicate that combined treatment in patients who are most refractory to treatment or who have residual symptoms is superior to either medication or CBT alone. Patients with long-standing depression can develop beliefs about depression and the future based on the life experience of having unrelieved, protracted, debilitating symptoms. These patients require rehabilitation and cognitive remediation. Patients with chronic depression often develop a view of themselves as “depressed people.” This self-image needs steady and persistent work in treatment to counter. Patients with chronic depression require specific instruction as to which behaviors to activate to increase a sense of pleasure and accomplishment. Chronically depressed patients benefit from a metacognitive approach that directs them to safeguard against the depressogenic “habits of mind” to which they will easily return without treatment. A purely biological explanation will often fall short for patients whose life experiences have taught them to see themselves as ineffective and have limited their choices socially and professionally. Patients with this type of depression frequently have limited memory about past events because of the mood disorder, and need to be reminded of prior instances of effective coping and interpersonal success.

Durability: The Challenge of Managing Depressive Recurrence Depression is a recurrent disabling condition. This is so frequently the case that patients with more than three episodes of depression in a five-year period are recommended to use antidepressant treatment indefinitely (Frank et al., 1990). One advantage of using CBT for acute depression is that it seems to provide protection from relapse in responders much more substantially than pharmacologic treatment—as much as a nearly 50% reduction in remitters

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with CBT (Hollon, Stewart, & Strunk, 2006). Continuation CBT, in group and individual formats, spaced over intervals, prevents relapse better than medication. Patients do have recurrence after CBT treatment as well, but at a far lower rate—estimated at approximately 54% within 2 years (Vittengl, Clark, Dunn, & Jarrett, 2007). A recent meta-analysis confirmed that acute response to treatment with CBT conveys a 61% chance of no relapse relative to pharmacotherapy (Vittengl et al., 2007). In addition to this statistical data indicating the significant advantage of CBT in conveying durability in depression, individual studies give us information about what we can do in practice to avoid problems that can derail patient recovery. One reason antidepressant treatment does not consistently produce a durable recovery from depression is nonadherence. Chronic antidepressant use may not be acceptable to many patients. A review of randomized controlled trials of patients on antidepressants with and without psychotherapy showed that patients remained in treatment and recovered more substantially when therapy was added to medication; this was particularly true in studies of more than 12 weeks’ duration (Pampallona, Bollini, Tibaldi, Kupelnick, & Munizza, 2004). Bockting and colleagues (2008) found that less than half of a group of patients with recurrent depression took their prescribed antidepressants, and only 26% of them took an adequate dosage. Even with adequate doses of medication, however, patients had a 60% rate of relapse in 2 years. This group also studied patients with repeated episodes of depression who discontinued antidepressants after a remission, and then were given eight CBT two-hour group sessions. The patients who received CBT had a recurrence rate of 8% compared to 46% of the control group. There was a significant protective effect 5 years later, although both groups had high rates of recurrence (75 versus 95%) (Bockting, Spinhoven, Wouters, Koeter, & Schene, 2009). A number of studies with CBT that successfully prevents recurrence apply sequential treatment—namely, CBT given after medication is either entirely or partially effective. This sequence allows patients to learn to prevent relapse with CBT methods at a time when they are not acutely and severely depressed. A prospective study of depressed inpatients found that although patients had a good short-term recovery, 40% relapsed in 15 months and 67 percent in 10 years (Kennedy, Abbott, & Paykel, 2003). Residual symptoms were strong predictors of relapse in this group (Paykel et al., 1995). Aftercare was carefully monitored in this review, and both self-report adherence and medication

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blood levels indicated that nonadherence did not account for relapse (Ramana et al., 1995). Paykel (2007) reviewed seven studies that evaluated the effects of CBT treatment on relapse and recurrence of major depression after treatment with antidepressants. All of the studies showed a statistically significant benefit of the addition of CBT, lasting long after therapy was discontinued whether patients were on or off medication. These seven studies varied in the timing of the CBT provided, the type of CBT (some group and some individual), the presence of residual symptoms in the patient groups, and the prior history of the recurrent nature of the depression. Fava and his group (Fava, Grandi, Zielezny, Canestrari, & Morphy, 1994; Fava, Grandi, Zielezny, Rafanelli, & Canestrari, 1996; Fava, Rafanelli, Grandi, Conti, & Belluardo, 1998; Fava et al., 2004) studied patients with multiple recurrent severe depressive episodes who responded to medication but who were unable to sustain remission when medication treatment was withdrawn. He treated patients after their symptoms remitted by tapering medication and aggressively targeting residual symptoms with CBT. Patients who received the combined treatment had a lower rate of relapse (15% versus 35%) two years later. A second group of 40 patients was enrolled and similarly withdrawn from medication and for 20 weeks had CBT for any residual symptoms plus “well-being therapy”—a form of therapy that aggressively targeted anhedonia and anxiety. This group was compared to a group who had clinical management alone. The CBT group had lower rates of relapse compared to the control group two years (25% versus 80%), four years (35% versus 70%) and six years (40% versus 90%) later. This small study points to key principles for combined treatment in patients with recurrent depression, namely: aggressively target residual symptoms with psychotherapy and medications, increase activity and broaden the range of activities in which patients participate; use graded exposure for residual anxiety, and instill good “psychological hygiene” practices (Fava et al., 1994; Fava et al., 1996; Fava et al., 1998; Fava et al., 2004). These procedures can help patients with recurrent depression achieve and sustain remission. A recent study also points to the speed of medication discontinuation as a potential factor in recurrence of major depression. Rapid discontinuation is associated with a much shorter interval in recurrence of depression (Baldessarini, Tondo, Ghiani, & Lepri, 2010). Providers must gradually taper antidepressants to obtain the most favorable outcome.

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CBT for depression appears to convey durability in a highly recurrent illness. First, CBT applied to the acute phase of depression is more durable than medication alone, both for mild to moderate and severe depression (Hollon, DeRubeis, et al., 2005). Second, a sequenced approach in which CBT is applied to residual symptoms after antidepressant treatment produces a more durable recovery. When performing CBT with depressed patients, it is critical to remember that underlying belief change is more correlated with the enduring effects of CBT than any other component (Hollon, Evans, & DeRubeis, 1990). Patients who have negative cognitive styles are at high risk for depression (Alloy et al., 2004). Patients whose depression is treated with pharmacotherapy are more likely to have dysfunctional attitudes reoccur when a sad mood is induced after recovery. Such an occurrence with a mood induction predicts relapse years later (Segal et al., 2006). Patients whose therapists pay attention to these dysfunctional attitudes and beliefs early in treatment are more likely to have improvement in their symptoms and sustained recovery (DeRubeis & Feeley, 1990). Patients who continue to use CBT coping skills independently are less likely to relapse after treatment is over, highlighting the importance of out-of-session practice (i.e., homework) (Strunk, DeRubeis, Chiu, & Alvarez, 2007). Because relapse is so common in depression treatment, therapists should emphasize the need to consistently employ strategies learned in the future. Medication treatment that has durable results after treatment is withdrawn may occur because the patient has an enduring change in her experience in the world. Recently, Tang and colleagues (2009) showed that some patients who responded to antidepressants also reported substantial changes in neuroticism and extroversion. These personality traits changed in a way that endured after medication was withdrawn. These changes could convey a protective effect with respect to relapse. Responsive patients could have a new experience in the world while on medication that teaches new skills, revises old rules and assumptions, and conveys subsequent “protection” against future episodes of depression.

HOW EFFECTIVE ARE ANTIDEPRESSANTS? Recently, several papers have questioned the effectiveness of antidepressants relative to placebo for mild to moderate depression. The findings of a megaanalysis of six placebo-controlled studies conducted between 1980 and 2009

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(Fournier et al., 2010) determined that patients who were severely depressed were much more likely to benefit from antidepressants relative to placebo (Hamilton Rating Scale scores of 25 or greater) than patients with mild to moderate depression. This study had some limitations in that only studies of two different medications (imipramine and paroxetine) were included in the analysis, and some studies with different methodologies were included. Nevertheless, in mild to moderate depression, it may be reasonable to consider a trial of psychotherapy as the first method of treatment. Many drug trials exclude milder depression from studies (Posternak, Zimmerman, Keitner, & Miller, 2002) so that patients with milder symptoms, who will not benefit from clinically prescribed antidepressants, are excluded from the study group. Therefore, we may have an exaggerated sense of the effectiveness of medication. The STAR*D study certainly confirms that in clinical practice, response rates to medication do not approach those found in efficacy trials. In addition to the Fournier study, Kirsch and colleagues (2008) analyzed data submitted to the FDA about fluoxetine, venlafaxine, nefazodone, and paroxetine using both published and unpublished data. They reported that initial severity correlates with response to medication (Kirsch et al., 2008). An additional review found that 31% of studies received by the FDA about 12 antidepressants were not published. Of those studies that were unpublished, all but three had negative or questionable results (Turner, Matthews, Linardatos, Tell, & Rosenthal, 2008). The authors of this review state that “the efficacy of this drug class is less than would be gleaned from an examination of the published literature alone.” Additionally, some authors have noted that when patients have had numerous episodes of use of antidepressants, they become less likely to respond to them in the future. Leykin and colleagues (2007) found that a higher number of patient prior exposures to antidepressant use predicted a lower response to medications but not to CBT. Given the recent findings of Harner’s group (Harner, O’Sullivan, et al., 2009), this nonresponsive group may represent a subset of patients who do not develop an initial change in perception and do not notice positive events at an increased rate when treated with antidepressants.

What Are We to Make of These Findings? First, most of us in clinical practice have seen the dramatic, life-saving effects antidepressants can have in some patients. And most of us in clinical practice also have had the experience of treating patients who derive little or no benefit

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from multiple trials of numerous agents. Initially, we might attribute this to nonadherence, or co-morbidity, but given the information above, we might also conclude that although antidepressant medications are of vital importance and are life-saving for patients who respond, there are limits to their efficacy. Furthermore, the durability of response with antidepressants is limited. It bears mentioning that there are also limits to the efficacy of CBT. If patients are not responding, we need to consider other evidence-based treatments for depression, such as interpersonal therapy (IPT).

SPECIAL ISSUES IN COMBINED TREATMENT FOR DEPRESSION When we consider what treatment to recommend to depressed patients, we need to also assess particular patient characteristics. The following issues must be assessed by all the patient’s treatment providers: 1. Is the patient suicidal? Patients with suicidal ideation require a detailed risk assessment and consideration of a more protected treatment environment. 2. Is there evidence the patient is bipolar? Remember that a substantial number of patients who present with major depression will have bipolar disorder. These patients require combined treatment to obtain the best outcomes. 3. Is the depression recurrent? If the patient has had more than one discrete episode of depression and the patient has had adequate pharmacological management of the depressive episodes, the addition of CBT after the patient improves may produce a more durable recovery. 4. Is the depression chronic? Patients who have longstanding depressive disorders that are either unresponsive or partially responsive to treatment may need to have both psychotherapy and pharmacotherapy to treat the depression and to rehabilitate the patient. 5. What is the severity of the depression? Patients with mild to moderate depression may achieve better results when treated with CBT alone. Patients with severe agitation, insomnia, and anhedonia may require combined treatment to forestall the psychosocial consequences and suffering that occur with depressive illness. In addition, the presence of psychosis warrants pharmacotherapy with antidepressants and

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an antipsychotic agent (or a second-generation antipsychotic alone or in combination with antidepressants), as there is evidence that psychotic depression is less responsive to psychotherapy or antidepressant treatment alone. 6. Is there a coexistent Axis II disorder? Behavioral activation and antidepressant treatment may be superior to CBT alone when patients have Axis II disorders and secondary major depression and cannot obtain longer courses of CBT. In a large study of severe depression, patients with co-morbid personality disorder responded better to medications than to CBT and sustained their response to medication (Fournier, DeRubeis, Shelton, Amsterdam, & Hollon, 2008). In a study of behavioral activation compared to CBT and medication, a subset of patients with extreme nonresponse did not respond as well to CBT as to behavioral activation (Coffman, Martell, Dimidjian, Gallop, & Hollon, 2007). The process of relationship building in patients with co-morbid Axis II disorders takes longer, and such patients may experience the emphasis on automatic thoughts in CBT as invalidating the actual struggles that occur in their lives. Therefore, “standard” CBT may need to be prolonged in such patients for successful outcomes. In addition to these more general issues, specific problems related to dual responsibility treatment of depressed patients benefit from our consideration. These include: • • • •

Working in collaborative care with primary care physicians Making behavioral activation more effective Handling the challenge of suicidal patients Managing depression in the presence of co-morbid anxiety

Collaborative Care With Primary Care Physicians The vast majority of patients diagnosed and treated for depression are treated in primary care settings. Olfson and Marcus (2009) studied the prescription of antidepressants in 2005 and determined that antidepressants were the most commonly prescribed drug class in the United States, but that only 19% of patients treated with these medications were seen by a psychiatrist. Additionally, they found that 13% of patients who receive prescribed mood

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stabilizers and antipsychotics receive them from their primary care physicians. As psychotropic medications have become safer to prescribe, patients obtain them in nonpsychiatric physician’s practices. Gene, a patient we met in Chapter 3, is typical of such patients. Gene is a 46-year-old man with a 20-year history of alcohol abuse. He stopped drinking two years ago, after his divorce. He attends AA meetings fairly regularly. When Gene was laid off from his job six months ago, he became profoundly depressed. He entered therapy and eventually was willing to consider taking antidepressants. He was given a prescription for sertraline by his primary care physician. Gene filled his first prescription and got good results, particularly with respect to relief from insomnia and suicidal thinking. He has not returned to his physician for a follow-up visit. Gene has been very ambivalent about taking medication, but has not discussed this in therapy. Many of his friends in AA are quite negative about the use of psychotropic medications, although his sponsor is quite supportive. Gene discontinued his sertraline abruptly after his first prescription ran out, and developed severe symptoms, as described in Chapter 3. A recent study in depressed geriatric patients in primary care practices who were provided a four-month primary care CBT intervention, both with and without antidepressants, showed significant patient improvement with the addition of CBT (Serfaty et al., 2009). Antidepressant prescription did not alter outcome in the improved group, but only one-fifth of the patients were prescribed a therapeutic dose. Medication treatment was naturalistic and not controlled. This data focuses attention on a particular problem in primary care treatment of depression: One must be certain that the patient is receiving adequate pharmacotherapy and that nonresponse is targeted when the patient is treated in primary care. Patients treated in primary care are frequently prescribed suboptimal doses of medication and do not receive close early monitoring for side effects and treatment response. The length of a typical office visit in primary care does not lend itself to an exploration of adherence problems. Additionally, psychopharmacological management of major depression has become far more complex. Many new medications exist, and novel strategies for augmentation have been developed. In primary care training there are limits to the depth of experience in any single subspecialty. More complex patients may require specialist consultation to obtain the best outcome. Katon and his group (1996) studied a structured manual-based depression treatment program, delivered by psychologists collaborating in primary care

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practices. This program included four to six contacts providing cognitive behavioral skills training to manage depression and promote adherence followed by telephone booster sessions. Patients had significantly improved adherence and symptom reduction. This was an onsite intervention, designed to integrate psychiatrists and psychologists in a primary care practice. This program also contained didactic sessions provided by psychiatrists for the primary care physicians about the prescription of antidepressant medication. Despite the effectiveness of programs like these for providing better depression management in primary care, dissemination of such programs is limited. This means that individual therapists must work collaboratively to educate primary care providers prescribing for their patients about the value of CBT interventions. This collaboration can increase physician-based education about depression and medications, improve communication about the value of careful adherence, and provide reinforcement for engaging in the activities of therapy. When patients receive similar information about what depression is and how it is effectively treated, in both their physician’s office and their therapy visits, recovery is more likely. Patients receiving medication in primary care settings require extra work regarding medication adherence in psychotherapy, because time is so limited with the prescriber. Primary care physicians may be unaware of the risk of depressive recurrence associated with rapidly discontinuing antidepressant medication, and therapists can help disseminate this information through collaborative work. A good working knowledge of the elements of adequate pharmacotherapy for depression and a relationship with the patient’s prescriber are extremely important when patients are recovering pharmacotherapy in primary care. When primary care physicians who are well versed in providing pharmacotherapy request that their treatment-resistant patients seek psychiatric consultation, it is common to find that patients can be reluctant to go. The extra expense and effort, the stigma, and, at times, the difficulty in finding a psychiatrist who has availability are disincentives to the depressed patient. When patients in this circumstance express ambivalence, therapists must be proactive and use CBT strategies to help patients get the help that they need. Another significant challenge in treating patients who receive medication management in primary care is communicating with the primary care team. Primary care physicians are frequently overscheduled and have little time to speak with other providers. Patience and persistence must be a part of the “toolbox” of therapists who seek the best possible care for their patients.

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Often, making an appointment with the primary care physician for a telephone consultation can decrease frustration and increase success.

Making Behavioral Activation More Effective Behavioral activation is a key component of CBT for depression, and can be a stand-alone treatment for acute major depression, with an efficacy similar or superior to CBT and antidepressant medication (Dimidjian et al., 2006). Standard CBT incorporates the key principles of behavioral activation by assigning behavioral experiments to depressed patients to test beliefs about fatigue and self-efficacy and by scheduling pleasurable activities. When behavior change produces results, cognitive change follows. Behavioral activation is particularly important in patients who have prominent anhedonia, decreased energy, and inactivity, as is typical in more severe depression. Behavioral activation is the most important part of early treatment in these patients. Its goal is to help patients break the cycle of inertia and avoidance that perpetuates the depressed mood state. Patients with depression avoid activity. Our cultural values frequently inculcate people with the belief they must “feel motivated” to start to engage in activity. This is, of course, not true, and such a belief is deadly in depression. Behavioral activation involves initiating action according to a plan, rather than waiting to be instigated by a “feeling.” In behavioral activation, therapists help the patient choose an activity that has value to the patient, break it into component parts, and then guide the patient to task completion, particularly targeting the thoughts and behaviors that lead to activity avoidance. The process involves assessing the patient’s current activity level, evaluating what the patient wants to do or no longer does, and developing a list of activities from least to most challenging to accomplish. Behavioral activation is akin to exposure to activity. As the patient makes efforts, the therapist identifies the existing barriers to progress and troubleshoots them with the patient. The therapist and patient must make a plan for the patient to initiate action even when the patient has negative thoughts and feelings. An explanation of the “action tendencies” of emotional states and the need to counter them can often help patients participate more readily in instigating activity. The patient with severe depression requires a more persistent, flexible therapist who does not abandon the effort to increase patient activity and decrease avoidance too soon. Patients may need to work at behavioral activation for a sustained period of time before inertia and anhedonia are defeated. Homework, including task assignment, completion, and participation in pleasurable activity,

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is even more critical in the patient who is functioning less well. This is a crucial time to exploit the advantages of two providers when the patient has them— each must inquire about assigned activities regarding mastery and pleasure, troubleshoot, cheerlead, and reinforce every effort made by the patient. Having two providers increases the opportunity to motivate the patient to engage in avoided activity. Successful treatment is more likely when the patient receives consistent and clear instructions about the importance of his efforts. A good example of the use of behavioral activation is with Alice, a patient who has had a partial response to medication given to her by her family physician. Alice is a 52-year-old single woman, the mother of two grown sons 32 and 27 years of age. She divorced their father when the boys were toddlers and managed to raise both children on her own, with little help. Despite her resourcefulness in caring for her sons and keeping the household together, Alice has always seen herself as a failure—unable to sustain a marriage and what she sees as a “normal” family life. Alice’s mother was depressed, and Alice was responsible for the care of her four siblings from early childhood. She had a tumultuous marriage. Her husband was alcoholic and verbally abusive, and she eventually left because she felt her sons were unsafe in the house. She holds herself responsible for the inability to repair her marriage. Alice has been depressed “forever.” She has never received treatment because she thought it made her a “weak person” to go to a psychiatrist or therapist. She worked steadily through her sons’ childhoods, but would come home at night and go straight to her bedroom to lie down after feeding the boys. After the boys graduated high school and left home, Alice’s life got progressively more constricted. She still works as a bookkeeper, but has no other recreational pursuits, feeling unable to have “the energy” for anything else. Her eldest son was recently diagnosed with melanoma, and he has asked her to help him care for his three sons. He mentioned to her that he wanted her to “do things” with them, not just “stay in the house.” Alice is terrified that she will be unable to manage this at her current level of energy and thinks that she will be “no fun.” She thinks of any activity as “too much of an effort.” Despite the fact that Alice’s sleep is reasonably good, she has poor concentration, interest, motivation, energy, and enjoyment. She always feels guilty and empty. Alice wanted to be able to be available for her grandchildren and son, so she sought treatment. Her family doctor gave her a prescription for sertraline, which she has taken for ten weeks. She was surprised that she had better concentration at work. Her interest and energy still lagged, however. At the

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suggestion of her primary care physician, she made an appointment with Dr. Peters, a psychologist. In her initial therapy session, Alice said that she was unable to think of “anything” that she could do for enjoyment. She said that “it’s all I can do to get through the day.” Dr. Peters asked her if she would be willing to read through a list of pleasurable activities in the session just to see if any of them sounded like they could be fun. Alice was surprised that such a list existed and even more surprised to see how long it was. Dr. Peters asked her to choose five things on the list that sounded like fun and that she could actually envision trying during the week. They scheduled these, and made a specific plan for Alice to try them, with some built-in reminders. The initial step was to see if doing these activities made Alice more or less tired. Alice returned the following week after trying three of the five scheduled activities. She played solitaire, did a Sunday newspaper crossword puzzle, and took a walk. Each activity was pleasant for her and did not tax her energy. However, she did not call her younger son and did not have lunch with her co-workers as planned. A closer look at these two activities was very helpful because it identified that Alice was most concerned that being with other people would “take too much out of her.” She was given a particular assignment to rate her energy on a scale of 1–10 after each interpersonal encounter in the next week to see whether this thought was true. Dr. Peters hoped that Alice would increase her socialization by performing this behavioral experiment. Alice is typical of patients with chronic depression; she copes by avoiding activity to manage her distress and in accord with beliefs that activity will worsen her condition. This avoidance and lack of engagement further confirm her beliefs about her helplessness and hopelessness and incur more losses in social and interpersonal domains. Therapists must increase activity in chronically depressed patients and persistently urge the patient to try more things, always tweaking the size of the intervention to the capacity of the patient. Behavioral activation is far more effective when sessions include writing down the key elements of the session and the homework assignment—written instructions regarding activities should occur in each provider’s office when the patient is in dual responsibility treatment, for optimal reinforcement. Therapists may also need to be creative in prescribing new activities for the patient. The Pleasant Events Schedule (MacPhillamy & Lewinsohn, 1982) is a wonderful tool to use in session to help the depressed patient remember previously valued activities or increase a repertoire of pleasurable activities.

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Another important resource is to keep free or subscription city or neighborhood newspapers and magazines in the office to stimulate interest in possible pleasant activities that the patient could try. It is important to consider the patient’s economic limitations when assigning pleasant events—a good exercise to practice to increase a repertoire of low-cost options is to list 50 pleasant activities available each for less than $5.00. Each provider must actively troubleshoot obstacles to activity in the session with the patient in collaborative care. What will interfere? Frequent and persistent attention to the sense of inertia and “not feeling like it” that is so pervasive in severe or chronic depression is required. Adherence work to the tasks of behavioral activation can be provided in pharmacotherapy sessions, just as adherence to medication can be a focus of psychotherapy sessions when two providers exist. Family members or other significant others can be ancillary supports to help encourage the patient to be more active and boost the effectiveness of behavioral activation.

Suicidal Patients Suicide is an obvious concern when treating a patient with major depression. The lifetime mortality rate for suicide is estimated to be approximately 10% in patients who are afflicted with major depression (Wilson, Valliant, & Wells, 1999). Furthermore, there are particular pitfalls to avoid when suicidal patients are seen in dual responsibility treatment. These pitfalls occur when communication between providers is poor and when there is no agreement about a consistent and coherent treatment plan. Providers need to involve family and significant others and have a clear plan for more aggressive and protected treatment when indicated. In the ideal circumstance, care providers will have been in communication with one another before any crisis occurs. If such communication has not yet occurred, and a patient is suicidal, it is mandatory to immediately do so. Integrated treatment, as discussed in Chapter 3, is remarkably helpful when patients are in crisis.

Communication During Suicide Crises in Dual Responsibility Treatment Patients who develop suicidal thinking mandate frequent and unambiguous communication between treatment providers. Because the psychotherapist is likely to have more frequent contact with the patient, she may be more aware of the patient’s state of mind and should take the initiative to contact the

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medication provider. Any new onset of suicidal ideation should trigger immediate contact. Both providers should review the current treatment plan, search for what may be missing from the conceptualization or plan, and determine whether there is a need to change the level of care, psychotherapeutic strategies, or pharmacotherapy. Any new collateral information or new risk factors that exist should be jointly discussed. Both parties must carefully consider how reliable the patient has been as an informant and as a partner following through with treatment agreements. Both parties should review together what information has been obtained in the ongoing suicide risk assessment. Assessing suicide risk is an area where the multiaxial DSM system can be helpful to clinicians as a tool to organize and consider data (see Table 5.1).

Table 5.1 Suicide Risk Assessment Axis I: Diagnostic Risks

Major depression and bipolar disorder Schizophrenia Anxiety disorders, especially panic disorder Substance abuse

Axis II: Diagnostic Risks

Borderline, antisocial, narcissistic personality disorder

Axis III: Diagnostic Risks

Pain Terminal illness

Axis IV: Current Stressors

Recent losses Isolation

Axis V: Level of Function

What is the trend over the past months?

Additional Risk Factors

Multiple attempts in past Age, gender Family history of suicide History of abuse

Cognitive Risks

Impulsivity Hopelessness Agitation Intent to die “Practice/rehearsal” of suicide plans Wish to be dead Specific plan and preparation Subjective rating of depression

Environmental Risks

Access to firearms Means available

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Risk factors can exist on each axis—a careful assessment will consider each, informed by the knowledge that the presence of risk factors on multiple axes exponentially increases the risk of suicide. An ideal use of a team of providers is to jointly review the risk assessment point-by-point to share information and assess the lethality of the patient’s current state. Once the patient’s level of risk has been determined, we can use the existing evidence about the use of CBT with suicidal patients to develop practical strategies to help us deliver effective collaborative treatment.

Evidence for the Use of CBT Strategies to Help With Suicidal Patients There are several pieces of evidence regarding the benefits of adding CBT to pharmacotherapy in suicidal patients. First, CBT is quite effective as a treatment for many of the Axis I disorders that increase the risk of suicide. A highly active, directive therapist who is hopeful and has a clear plan is a powerful force for change. Patients in combined treatment often need to wait several weeks before they begin to benefit from medication in a sustained way. Hopelessness and suicidal thinking during this period can be reduced by a good therapeutic alliance with providers. This means that caregivers must be particularly mindful of the quality of their engagement with the patient who is suicidal and hopeless. Providers must present evidence that depression improves with the treatment specified. Accurate empathy in such circumstances is a must— confidence in the treatment is important, but appreciation for the struggle of the patient is, too. In addition to the nonspecific protective effects of CBT for depression, two forms of CBT have been shown to be specifically effective in reducing the frequency of suicide attempts in patients who are previous attempters. Brown and colleagues (2005) found that a ten-session CBT intervention reduced the number of patients with repeat attempts in patients with a previous suicide attempt. Just over 24% of patients in active treatment made a repeat attempt, compared to nearly 42% of patients receiving treatment as usual. This was a study of a heterogeneous group of patients who had multiple diagnoses and who presented for care at the time of a suicide attempt. A second type of CBT that has been specifically shown to reduce the frequency of suicide attempts is dialectical behavior therapy (DBT). DBT is a form of CBT designed to treat patients who have both Axis I and Axis II diagnoses and chronic suicidal ideation and behavior. It was initially studied

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in chronically suicidal patients with borderline personality disorder who had co-morbid Axis I disorders. DBT effectively decreased the percentage of patients with repeat suicide attempts in one study from 100% of the treatment-asusual group to 26% in those patients who received DBT (Linehan, Armstrong, Suarez, Allmon, & Heard, 1991). Tarrier, Taylor, and Gooding (2008) in a meta-analysis reviewed 28 studies of CBT specifically employed to reduce suicidal behavior and found that individual CBT treatment for adults was significantly effective compared to no treatment and treatment as usual. Specific features of these forms of CBT can help us tailor our approach to suicidal patients in the clinical setting. First, when a patient has a history of self-harm, there must be a thorough exploration of the triggering situations that precipitated this behavior. Brown et al. (2005) used stress inoculation and cognitive rehearsal of new responses to triggers in patients with suicidal behavior after the suicide crisis had passed. The goal of this intervention was to help patients not conclude repetitively that suicide was the best option when triggers occurred. Suicidal behavior can be countered by attending to problem-solving deficits and rehearsing new skills in triggering life circumstances. The Brown protocol also focused attention on giving the patient the task of constructing a “hope box” or “survivor kit.” The purpose of this intervention is to make the patient construct a tangible and concrete reminder of the reasons to stay alive. These physical reminders powerfully establish cognitive and emotional connections to deterrents to suicide. This box can include photographs, Bible verses, items that represent future goals, and representations of valued activities and loved ones to sustain hope and the desire to stay alive when strong ideation occurs. DBT employs multiple approaches to help patients reduce and tolerate distress. A key principle of DBT in patients with borderline personality is that they are vulnerable to excess emotion and engage in self-destructive behaviors in suicide crisis situations to alleviate intolerable emotional pain. The therapist teaches the patient skills to regulate emotions and tolerate situations that they cannot immediately change to replace the suicidal behavior that generally occurs. Remediation of skill deficits in suicidal patients who are depressed may also be of benefit to increase their tolerance for emotional pain. In the risk assessment of a suicidal patient, possible triggers such as symptom intensification (e.g., insomnia) can be identified, and then the patient can be provided more customized pharmacological interventions. In collaborative

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treatment, the medication provider can report any history obtained of stressful interpersonal events to help the therapist augment behavioral plans to deal with suicide triggers. Strategies to protect patients with suicidal ideation are listed in Table 5.2. Another important tool to help suicidal patients reengage more hopeful thinking is when providers identify strengths and prior effective coping by the patient. This develops more flexible thinking and helps the patient to consider other options beside death as a solution to life’s problems. Patients who are acutely suicidal often underestimate their capacity to cope with adversity and benefit from a guided exploration of past success. Every patient encounter should contain work to increase the patient’s desire to live. Remember that past attempts and hopelessness (Alloy et al., 2004) are key variables that influence suicidal ideation, intent, and completion. Patients who are hopeless and suicidal are often unable to use thought records on their own, or may be too new to treatment to have the skills to independently disengage from hopeless thinking. In-session work to target this thinking is of paramount importance, followed by written reminders of what is discussed in the session. It is particularly important to assess and target any hopelessness about treatment. Each visit provides an opportunity to help the patient see more solutions to problems in “real time.” Specific, detailed, and written plans for out-of-session activities must be made in each treatment encounter. For

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example, telling the patient, “Have some fun this weekend,” is far too vague. Previously valued activities, especially ones that include other supportive people, must be planned (like “I will call Jenny twice and I will work for ten minutes in the yard every day”). Modifying any cognition that leads to suicidal behavior is another important strategy to decrease risk in depressed patients. First, each partner of the care team must be willing to talk about the patient’s suicidal thinking and uncover thoughts and beliefs that put the patient at risk. Both providers must take a careful history of the thoughts and beliefs that occur prior to attempts or strong ideation. This will lead to a tailored conceptualization of the patient’s suicide crisis. Frequently, therapists can be tempted to avoid this when the crisis is less acute because of anxiety and discomfort, but specific information about this event is enormously important to future prevention. Therapy must engage the patient and explore the patient’s ideas about the actual aftermath of suicide. Patients often romanticize the idea of death (particularly young adults and adolescents) and neglect to consider the finality of death. Standard methods of cognitive remediation can replace this misconception with a more accurate, wider view. Countering the idea that suicide is a desirable solution and generating reasons for living decreases the risk of death. Any increase in the patient’s belief in prospects for a different future is progress. Once suicidal beliefs are successfully identified and challenged in session, the patient must have a written card with the suicide belief reframed and a definitive written crisis plan (see Table 5.3), as the following case example illustrates. Amy is a 28-year-old woman with a history of suicidal behavior and major depression. She particularly flounders when she has problems in relationships at work. She is in outpatient treatment with a psychiatrist, Dr. Roberts, for medication (venlafaxine 225 mg) and a psychologist, Dr. Smith, for therapy. Amy called Dr. Roberts in crisis after her current boss, Tom, called her into his office and yelled at her about a report that she had written. She told Dr. Roberts she wanted to make an immediate change in her medication. Dr. Roberts assessed the situation and determined that Amy had vague thoughts of “not wanting to be here” with no specific plan. Dr. Roberts remembered that Amy had several impulsive overdoses in the past after work crises, each while intoxicated. He asked Amy if she had contacted Dr. Smith. Amy had not, and said “it just seemed pointless” to talk about her situation. Dr. Roberts reminded Amy that she had had this reaction several

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times before when she was in trouble, and that she’d felt better after talking it out. He also told Amy that he did not think medication could make much difference in the short term. He asked if she would call Dr. Smith and then get back to him. She agreed to make certain she had a friend stay with her that night. Amy said she couldn’t avoid it because her sister was in from out-oftown to visit. Dr. Roberts received a call later from Amy that she had phoned Dr. Smith’s service. Dr. Roberts called Dr. Smith as well to share his impressions about Amy’s phone call. They discussed the treatment plan—Dr. Smith would talk with Amy via telephone the following morning and would call Dr. Roberts that evening if the telephone conversation that she had with Amy indicated that Amy needed more intensive intervention. Dr. Roberts and Dr. Smith discussed Amy’s need to increase her tolerance for interpersonal triggers for suicidal thinking and to discuss how alcohol use was a trigger, too. Dr. Smith called Dr. Roberts later to say that Amy had phoned, was able to come up with reasons to stay alive in the face of a work conflict, and had developed a coping card to review these reasons until her session the next day (see Table 5.3). This brief vignette illustrates some key principles for collaborative care in suicidal patients. Dr. Roberts and Dr. Smith have previously made contact and agreed about the conceptualization of Amy and about each person’s role in her treatment. Amy is aware of, and consents to, their communication. They collaborated about when to communicate about Amy and when further specific interventions would be employed. They reached a joint

Table 5.3 Amy's Coping Card Negative belief: If I get yelled at by my boss, I should kill myself. Feeling: Ashamed, sad Positive belief: I have lived through feeling ashamed. Everyone has gotten yelled at by the boss sometime. My family would be devastated if I kill myself. I might feel like a failure, but my job is not worth dying for. Tom might not even know that I am so upset by this. If I cannot stop the suicide thoughts, here is my plan: I will not drink. I will call Dr. Smith (xxx-xxx-xxxx) or Dr. Roberts. (xxx-xxx-xxxx). If I cannot reach either of them immediately I will call the crisis line. (xxx-xxx-xxxx). If this is not sufficient to stop me from acting on my thinking, I will go to the emergency room at Doctors' Hospital.

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conceptualization of the antecedents of Amy’s suicidal behavior and supported each other’s efforts in helping Amy to find alternative solutions. They identified safety precautions for Amy to take and reminded her of prior instances when she used CBT methods to her advantage. And finally, they enumerated ideas and plans for Amy to use when she encountered triggers for hopelessness and suicidal thinking. An advantage of dual responsibility treatment when communication is clear and you have a trusted partner in the patient’s care is that there is a second observer to gather information about the patient, and an additional support for the patient as well as for the provider. This resource can help us to manage patients more effectively and support us as we work with difficult suicidal patients. Clinicians working with suicidal patients often have understandable reactions to working with them—a partner in the patient’s care can serve as a “sounding board” for thoughts and ideas about the patient and the treatment plan. A particular concern about dual responsibility treatment and suicidal patients occurs when managing patients whose pharmacological treatment is being provided by a primary care physician. Suicide risk assessment is variably conducted in primary care (Smolders, Laurant, Akkermans, Wensing, & Grol, 2008), and patients can be seen infrequently and for very brief visits. Therapists who are seeing such patients may decide to refer the patient for psychiatric consultation both to determine whether the level of care is appropriate and to consult about whether suicidal thinking merits a change in pharmacotherapy or even requires hospitalization.

Managing Depression in the Presence of Co-Morbid Anxiety Depression that is complicated by anxiety is a complex clinical problem. Patients who struggle with both problems are common and require more attention regarding residual symptoms and treatment attrition. Alex, a patient we met in Chapter 4, is a patient with severe and chronic panic disorder and co-existing major depression. He cannot really determine which came first—although he is certain his panic disorder started when he was 22. He has had mood problems “as long as (he) can remember.” Alex has never had much relief from his symptoms. He is functioning enough to hold down a job as a school janitor. His social interactions are almost exclusively with his mother, and his two sisters and their families. He is doing a bit better and is somewhat less depressed because he stopped drinking after being charged with a DUI, six months prior to seeking treatment.

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Alex has never received any psychotherapy for his condition. He has received a variety of antidepressant prescriptions from his primary care physicians over the years. He has taken one or two pills of each of these prescriptions and thrown the rest away; he did not even fill the last two. He has not told his primary care providers about this. Alex decided to come for therapy after seeing a television infomercial about psychotherapy for anxiety. After he stopped drinking, his panic worsened such that he does not want to leave the house, and he has started to call in sick from work. Alex started psychotherapy with fairly negative expectations. He said he could not “imagine being different.” He understood the idea of exposure, but at every attempt to practice it, he was so terrified he jettisoned the effort. Thereafter he was far more depressed and demoralized. He was called to his supervisor’s office and informed that if his attendance did not improve he would be fired. This led to a reevaluation of the possibility of combined treatment. Alex’s presentation and history illustrates typical features in patients with co-morbid anxiety and depression. He has hopelessness about treatment and substantial impairment in psychosocial function. He has a history of co-morbid alcohol abuse. His anxiety is impacting his life such that he sustains continual losses. Standard CBT interventions have been difficult to implement because of the severity of his anxiety. The presence of anxiety is a key mediator of response in depression. Patients with depression typically seen in clinical practice have a large number of anxiety symptoms and may respond best to a combination of targeted interventions, including CBT. In the STAR*D study, patients with anxiety were significantly less likely to respond to treatment, and were far more likely to have adverse medication effects. Patients in this study with co-morbid anxiety had more psychosocial consequences of their illness—they had more unemployment and less educational achievement. The STAR*D study did not exclude patients with Axis I anxiety disorders that were co-morbid with depression, so anxiety symptoms could be quite severe and prominent. Up to 31% of patients in the sample had problems with anxiety (Trivedi et al., 2006) and these symptoms increased the chance for relapse (Fava et al., 2008). In the Keller study, the presence of anxiety symptoms predicted the need to combine medication with psychotherapy, compared to psychotherapy alone, in order to achieve a response (Ninan et al., 2002).

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Fava and colleagues (Fava et al., 1994; Fava et al., 1996; Fava et al., 1998; Fava et al., 2004), in the studies of patients with chronic depression previously discussed, specifically targeted symptoms of anxiety in depressed patients. His protocol used exposure-based treatment to deal with residual symptoms of anxiety that restricted patients’ lives following the taper of antidepressants. Therefore, it appears that specific psychological and/or pharmacological interventions that target anxiety symptoms in depressed patients may improve treatment response. An initial intervention with patients who have co-morbid anxiety is to teach them that therapy takes longer, so persistence and patience are required. Patients who are depressed and who have prominent anxiety symptoms respond less easily to treatment, so the patient, therapist, prescriber, or all three may discontinue treatment efforts too soon. When both anxiety and depression co-exist, symptoms are more severe, patients are more likely to have suicidal ideation, and they have higher ratings on standardized instruments that measure depression and anxiety severity (Brown, Schulberg, Madonia, Shear, & Houck, 1996). Another important aspect of treating patients with combined symptoms of depression and anxiety is determining which symptoms to treat first. Patients benefit if treatment systematically approaches problems and if they learn one thing at a time. Determining which problem should be treated first and working to motivate the patient to stick with interventions until they have an impact is important. Patients with anxiety and depression have a “double dose” of problems that can impede concentration and memory, so they may require much more time to educate, and they will need written reminders and smaller amounts of information per session. Particular attention must be paid to the role of anxiety in increasing avoidance behaviors—for example, if a patient is too anxious to go out with friends, this can interfere with a behavioral activation plan. Most patients intuitively understand the principles of exposure—if you ask them how to contend with a snake phobia, they will know that confronting the feared stimulus is the way to accomplish this. This principle can be consistently discussed in single or combined treatment with the anxious and depressed patient, and every small effort the patient makes to counter fear must be reinforced. In anxious and depressed patients in combined treatment, providers must aggressively target adherence and specifically attend to side effects. Explaining what to expect (and giving specifics about the actual safety of medication) can

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be key to adherence. A consistent and persistent focus on adherence is the most effective means to help the patient stay on medication. As this chapter illustrates, we have many effective weapons at our disposal to treat depression. Despite this, patients are frequently incompletely or inadequately treated, and evidence-based care is provided far less than it should be in such a devastating illness. Our task as informed clinicians, in addition to treating our patients, is to educate other care providers about the effective management of depression whenever possible.

Combining CBT and Medication: An Evidence-Based Approach by Donna M. Sudak Copyright © 2011 John Wiley & Sons, Inc.

CHAPTER

6 Combined Treatment for Bipolar Disorder OVERVIEW Bipolar disorder is a severe, recurring mental illness that often begins in young adulthood (before the age of 20). It has significant psychosocial consequences for the patient and his family. The essential features of the disorder are episodes of distinct mood dysregulation with interepisode recovery. At least one episode must be manic or hypomanic to qualify for the diagnosis. Mania and hypomania have clinical characteristics of elevated, expansive, or irritable mood, increased goal-directed or pleasure-seeking behavior, poor judgment and insight, derangement of sleep and appetite, and problems with attention, memory, and thought distortions. Patients with mania have accelerated speed of thought. Many bipolar patients have attitudes about positive mood states that make treatment difficult (Lam, Wright, & Smith, 2004). Co-morbidity with anxiety and substance use disorders is common and often complicates treatment. Despite the dramatic presentation of mania and hypomania, patients who are bipolar spend a much greater percentage of the illness in the depressed state (Alda, Hajek, Calkin, & O’Donovan, 2009). The illness requires longterm medication and psychotherapeutic management, and the heterogeneous nature of the disorder (i.e., numbers and types of episodes, triggers for episodes) means that individualized case conceptualization and treatment planning are important elements for success. Furthermore, bipolar disorder, like all mental illnesses, happens to a person—and personality disorders and interpersonal issues are substantial factors affecting the outcome of the illness and, thus, significant parts of formulating a treatment plan. 81

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The diagnosis of bipolar disorder also conveys a substantial risk for severe complications. Suicide is a high-risk concern in these patients, and 15 to 20% of untreated patients with bipolar disorder die by suicide (Baldessarini, Pompili, & Tondo, 2006). Suicide occurs both in the manic and depressed phases of the illness, but is far more likely to occur in the depressed phase of the illness. Patients who are bipolar have an elevated risk for medical comorbidity (i.e., cardiovascular illness, HIV infection, hepatitis C infection) and psychiatric co-morbidity (i.e., substance abuse or dependence, anxiety disorders), which complicate management. Depression in bipolar disorder is phenomenologically similar to major depression, except for the tendency of some patients who are bipolar to sleep and eat more rather than to have insomnia and anorexia when depressed. Severe episodes of mania and depression can have accompanying psychotic symptoms, including delusions and hallucinations. Women with bipolar disorder are at particular risk for postpartum exacerbations of their mood symptoms and for postpartum psychosis. This chapter will describe the evidence for combined treatment with CBT and medication for bipolar disorder and review other forms of therapy that have been shown to be effective in helping patients with this difficult and dangerous illness. Clinical illustrations of patients that underscore the benefits and difficulties in collaborative treatment will be presented.

EVIDENCE FOR USE OF COMBINED TREATMENT IN BIPOLAR DISORDER Despite the fact that we have several powerful pharmacological tools to combat the debilitating mood cycles in bipolar disorder, response to treatment with medication alone is far from optimal. Recovery from acute episodes of mania is a lengthy process, and outcome is often poor. Patients fully recover function after hospitalization from mania only 25% of the time (Keck et al., 1998). Full recovery from bipolar depression is also infrequent compared to full recovery from unipolar depression, and antidepressants are not as effective as a treatment (Sachs et al., 2007). The prediction of recovery from bipolar disorder assumes full adherence to medication regimens, which happens less than half of the time (Colom, Vieta, Tacchi, Sanchez-Moreno, & Scott, 2005). The difference between efficacy and effectiveness in the “real world” of managing bipolar patients is clear. Adjunctive psychotherapy is the bridge

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whereby both the subthreshold improvement produced by medication and the substantial problems with adherence can be addressed. Since patients who have residual symptoms are more likely to have recurrences (Perlis et al., 2006), closing the gap toward recovery has enormous benefit to the patient by increasing function and preventing further episodes. Miklowitz (2008) reviewed the evidence base for using adjunctive psychotherapy for bipolar disorder and found that 17 of 18 randomized controlled trials have shown that combining treatment with psychotherapy can forestall relapses and shorten episode length. He also found that over a two-year period after psychotherapy ends, there is a sustained benefit to patient psychosocial functioning. Several different varieties of psychosocial interventions have been shown to be effective in clinical trials for patients with bipolar illness. Although this chapter will focus its attention on combining CBT with medication for patients with bipolar disorder, the choice of which method of psychotherapy to be employed should be individualized depending on availability and on the circumstances, abilities, and preferences of the patient. At present, the state of the evidence is insufficient to say that one of these evidence-based therapies is more effective than another. Very few studies exist that compare effective adjunctive psychotherapy treatments for bipolar disorder. However, STEP-BD, a large, practical clinical trial to determine the best means of combating bipolar depression, did so. This study compared family-focused therapy, interpersonalsocial rhythm therapy, CBT, and a psychoeducational control. STEP-BD was not designed to evaluate treatment effects on relapse-prevention or to decrease mood episodes, but was designed to evaluate the most effective way to produce recovery from bipolar depression. All of the active treatments tested produced faster recovery than medication alone, with no differences between groups, and patients in active psychotherapeutic treatment had better interpersonal function than patients who did not have treatment (Miklowitz et al., 2007). Thus, an older adolescent in a highly critical and emotional family may benefit more from family-focused therapy (FFT), whereas a single, extremely depressed bipolar woman with a great deal of negative thinking may benefit more from CBT strategies. Until we have a more comprehensive view of the evidence, a common-sense approach to the selection of treatment should prevail. All of the psychotherapies for bipolar disorder shown to be beneficial have some similarities, as reviewed by Lam and colleagues (Lam, Burbeck, Wright, & Pilling, 2009). The treatments they reviewed included complex psychoeducation, cognitive-behavioral therapy, family-focused therapy, and interpersonal-social

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rhythm therapy. The review identified these common themes in each of the treatments: the use of a stress-diathesis model, a substantial focus on psychoeducation and medication adherence, an emphasis on teaching patients to self-monitor, and creative lifestyle modifications to produce a regular and predictable structure to help the patient maintain a stable mood. Additional features identified as similar and effective in each of the therapies included problem-solving and promotion of relapse prevention. This meta-analysis indicated that augmenting medication treatment with one of these systematically derived therapies significantly improved patients’ function and symptoms and delayed or prevented relapse, compared to control groups. Studies reviewed by this group were of therapy both delivered in groups and individually, with patients treated in different phases of the illness. Thus, until we have clearer data, a “custom-tailored” approach as to which format to choose, taking into account the patient’s history, particular symptoms, and preferences, makes sense. The common outcome of all the successful randomized controlled trials of psychotherapy as an adjunct in bipolar illness is that psychotherapy treatment improves function and decreases bipolar disorder relapse rates at least for at least 12 to 30 months after treatment (Miklowitz, 2008). Patients with prominent manic symptoms clearly benefit more from approaches that enhance social and interpersonal stability and regular structure of circadian rhythms. Adherence to medication regimens needs to be a predominant feature of any combined approach.

TREATMENT OF BIPOLAR DISORDER Engagement The initial phase of work with a bipolar patient involves establishing an accurate diagnosis and educating the patient and family about the meaning of the diagnosis. Differential diagnosis in this illness is often complex because of the interplay between co-morbid psychiatric conditions (e.g., attention-deficit hyperactivity disorder, substance abuse) and because patients who are manic often imperfectly recall episodes of mania. Additionally, patients may conceal symptoms of mania because they feel ashamed about their behavior during episodes when it has been so out of control or socially undesirable. One reason the diagnosis of bipolar disorder is frequently delayed is because patients who are bipolar begin to manifest the disorder in adolescence or young adulthood, and the symptoms are mistaken for typical adolescence. An early age of onset also

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means that the patient’s developmental milestones are derailed (e.g., career development, education, interpersonal skill development, identity consolidation, and emancipation). This means that therapy must attend to the patient’s skill deficits. Additionally, because there are important genetic contributors to the illness, patients may have relatives with the illness (and beliefs about the illness based on that experience) or may have the daunting task of integrating the knowledge that the offspring they have had prior to diagnosis or future offspring could be similarly afflicted. The following case example illustrates these common presenting issues. Carol is a 45-year-old woman who has a diagnosis of rapid-cycling bipolar disorder. She first became aware of having mood problems in her early teens. At that time, she had episodes of sadness and low energy, severe anxiety, and sleep and appetite disturbance. She often thought about killing herself, but told no one. In high school, this became much worse, and her anxiety was so severe that for two semesters she withdrew from school and was taught by a private tutor at home. Her family told her that this was “just a phase” and that she was “shy” and would recover. When she was 19, Carol finally completed high school, a semester late. She was accepted to a college close to her parents’ home, but decided to try and live in the dorm. Carol had a few close friends, but had never dated. At school, she started to go to parties in her dorm, and would drink “to relax and fit in.” After homecoming weekend, when she had stayed awake all night at parties for most of two nights, Carol had her first manic episode. Her roommates called campus police after three days because Carol was hallucinating, and they were frightened. Carol was hospitalized for the first time. As her symptoms resolved, Carol was devastated by what had happened. She told the psychiatrist in the hospital that she had spent much of her adolescence worried that she would be “just like (her) crazy grandmother.” Carol’s grandmother had been in a state hospital for most of her adult life, and had committed suicide while in the hospital. Carol’s grandmother had been placed in the psychiatric hospital after she had delivered Carol’s mother. Three days after returning home from the delivery, she attempted to murder her infant and her other three children because she believed they were possessed by the devil. Her grandmother never lived with the family again. Carol’s presentation is striking because of the early onset of her symptoms, the developmental delays so characteristic of many bipolar patients, the use of alcohol to mitigate anxiety, the exacerbation of her symptoms in response to

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sleep disruption, and the pronounced family history. She presents many challenges with respect to helping her to attain stability and build a satisfying and productive life. The goals of treatment in a patient like Carol are several: to stabilize an acute episode, to prevent future episodes, to rehabilitate the patient, and to help her to have a well-informed, healthy perspective about the illness.

Acute Treatment In bipolar mania, medications remain the primary treatment. There is no evidence that any form of psychotherapy alone can sufficiently end a manic episode. Combined treatment is essential in this phase of treatment, however. Patients who are manic or hypomanic benefit from consistent support, gentle redirection, limit setting, and reality orientation. The establishment of a therapeutic relationship with brief empathic contacts can be extremely helpful at this time, and a relationship with the patient’s family and/or significant others can begin, grounded in support and education. Skilled interventions are needed during manic episodes to help persuade the patient about the usefulness of medication and to accept the reality of having an illness. Mood stabilization and restoration of sleep are the initial goals. This is generally accomplished by using medication—generally lithium, valproic acid, and/or a second-generation antipsychotic. Additional treatment with other anticonvulsants and/or antianxiety and hypnotic agents may also be necessary if the symptoms remain uncontrolled by the first-line medications or if the patient has mixed states or rapid cycling of mood. Acute treatment of bipolar depression frequently requires combined treatment. Antidepressants are less likely to be effective in bipolar depression. They can also have the possible unintended effect of producing a mood switch and inducing mania or hypomania, or changing the pattern of the patient’s mood episodes to one of rapid cycling. When antidepressants are used to relieve depression in bipolar patients, it is important to taper them slowly, as bipolar patients are more prone to recurrence of depression when antidepressants are rapidly tapered (Baldessarini, Tondo, Ghiani, & Lepri, 2010). Cognitive and behavioral interventions can be invaluable here as a means of relieving debilitating symptoms and improving function.

Long-Term Treatment Ongoing pharmacological and psychological treatment of bipolar disorder has the goal of preventing further episodes and maximizing the patient’s level

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of function. Pharmacologic treatment alone, in the long term, is less than satisfactory. Despite good data about lithium as a means to prevent episodes of mania and suicide (Tondo, Hennen, & Baldessarini, 2001), more than 90% of patients experience recurrent episodes of illness once diagnosed (Soloman, Keitner, Miller, Shea, & Keller, 1995). Residual symptoms are a substantial burden to patients with bipolar disorder. Subsyndromal depression exists 30 to 50% of the time in bipolar I patients (Huxley & Baldessarini, 2007). The burden of depressive symptoms in these patients causes substantial functional disability and suffering and likely is a factor in poor adherence to medication. Recurrence is significantly associated with residual mood symptoms (Perlis et al., 2006).

CBT FOR BIPOLAR DISORDER There are several detailed treatment manuals to guide clinicians who wish to add CBT psychotherapy to the tools they employ with patients with bipolar disorder (Basco & Rush, 2005; Newman, Leahy, Beck, Reilly-Harrington, & Gyulai, 2001). The following section provides an overview of the particular clinical features that distinguish CBT for bipolar patients and examples of combined treatment in action. The type of clinical intervention selected for a new patient with bipolar disorder varies depending on the acuity and severity of the patient’s mood state, the type of mood state, and the history of the patient’s illness. Patients with very severe mania or psychosis will require brief, supportive, reality-focused interventions until pharmacological management decreases the intensity and severity of their symptoms, regardless of whether they are inpatients or outpatients. The patient newly diagnosed with bipolar disorder requires a substantial amount of support and education, as does his or her family. In addition to coping with the symptoms that exist and the psychosocial consequences of the episode itself, which are often severe, patients also must accustom themselves to the reality of living with a chronic mental illness. This change in self-perception is an existential crisis for many—the shift from “well” to “ill” adds an additional burden and happens in the context of the patient’s belief systems about the diagnosis of bipolar disorder, doctors, psychiatrists, mental health, therapists, and medications. Bipolar disorder is chronic, serious, and life-threatening. The need to integrate the diagnosis into one’s self-perception would be difficult in a normal state of mind, but patients frequently have the

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additional burden of needing to understand and come to terms with this diagnosis during an episode that decreases concentration, attention, and memory. The episode itself can also alter the patient’s capacity to process information accurately because of the mood state. Depression, for example, can make the patient selectively attend to negative information about the diagnosis and its significance for her future. Therapists, therefore, must keep in mind that they will likely need to revisit the educational components that are so vital to adequate patient participation. Patients may have an understandable wish to deny or avoid the diagnosis, and rehabilitation must occur when the patient’s cognitive status is less severely compromised by the illness. Full recovery of cognitive function can take months, particularly when the patient is in a manic phase of the illness which involves psychosis. Inform the patient that the information will take time to “sink in.” You can pace the educational material by monitoring patient feedback. Therapists must also actively advocate for patients against the stigmatization and discrimination that they face. The patient and the patient’s family can connect to advocacy groups that can provide them with a community of support. Along with education, an early focus of treatment is to have the patient and his family retrace the patient’s particular symptoms with a timeline. Obtaining as much collateral information as possible is vital in order to help recognize particular triggers for episodes and subtle prodromal signs. Patients are often unaware of such signs and symptoms because of their mood state. This history will facilitate the development of a problem-solving approach to target specific prodromal symptoms that occur for the patient and avoid the progression of episodes of depression and mania whenever possible in the future. When patients come to therapy already diagnosed with the disorder and are in a more stable mood state, it is helpful to have them relate their understanding of the illness. This process will allow you to fill in any gaps in their knowledge or correct any misconceptions they have about the disorder. The next step is to review carefully the history of mood episodes over time and how these related to particular life events and pharmacologic treatments. This review may require patience and often entails obtaining medical records from other care providers and institutions. This can be frustrating and timeconsuming, but it is worth the effort. The process of constructing a timeline of the patient’s moods and symptoms helps the patient and therapist. Patients recognize the connection between particular events and behaviors and the

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development of mood episodes. Therapists can hone in on the prodromal symptoms that have the most salience to trigger relapse. The next step is to aggressively problem-solve with the patient what to do differently when these prodromal symptoms occur. Anticipatory guidance is a very important component of relapse prevention in bipolar patients. Carol was able to do this with her therapist. Carol and her therapist reviewed each of the events leading to her hospitalizations for mania. Her initial episode of mania was triggered by several nights with minimal sleep. Carol also had a history of developing hypomania when she did not get sufficient amounts of sleep—usually nine hours or so per night. Sleep disruption generally began when Carol would become overstimulated by activities in the evening and then stay up and work until after midnight. Eventually, when Carol would go to bed after working too late, she would be unable to fall asleep. This habit made Carol’s schedule erratic and was a factor in the development of episodes of mania. Carol’s treatment plan included the need to problem-solve and implement a regular bedtime routine that avoided these episodes and to have a “fail-safe” option to use medication at bedtime if the plan was unsuccessful.

Goals and Targets of Treatment The goals of treatment with CBT in bipolar disorder are: • To provide psychoeducation. • To enhance adherence to medication regimens and lifestyle modifications to maintain a euthymic mood state. • To teach the patient self-monitoring and self-observation for subtle prodromal signs and symptoms of mania or depression. Thereafter, the goal is for the patient to develop a plan with the therapist to prevent relapse as often as possible when prodromal symptoms occur. Patients, family members, and other supportive individuals are active participants, working as a team with the therapist and patient whenever possible. Many patients benefit from contingency plans that incorporate the support of significant others in the event of symptoms. Because bipolar disorder often presents in young adults, individual case conceptualization is crucial to pinpoint patient strengths that can help with problem-solving and the active coping so necessary to the optimal management

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of the illness. The conceptualization must also identify particular developmental deficits that must be corrected to enhance function. For example, if the illness begins in the middle teens, interpersonal communication skills (such as assertiveness) that would typically be learned at that time could be lacking. Family members may also require assistance to navigate the emancipation of a young adult with bipolar disorder. If they have a child who has had severe symptoms and many hospitalizations, they may be reluctant to allow the patient to have sufficient age-appropriate autonomy. The following patient example illustrates typical interpersonal problems and developmental delays that can occur in conjunction with bipolar disorder. Carol developed her first depression early in her teens and was hampered by symptoms through much of her high school years. She spent little time out of the house and had few friends. After her initial hospitalization, Carol was too demoralized to return to college and instead went to a community college to learn computer programming and word processing skills. She obtained a job at a law firm doing word processing and data entry after she graduated. Carol always felt out of place at work—she did not feel comfortable initiating conversations with her co-workers, even though they were very friendly. Her treatment goals included learning to be more at ease in social situations. When her therapist discussed with her the idea that she may be less comfortable in these circumstances because she never had the opportunity to learn how to be with her peers, it was a revelation to her. Carol was more able to invest herself in role-play and behavioral experiments to see if she could learn some new skills.

SPECIAL ISSUES IN THE COMBINED TREATMENT OF BIPOLAR DISORDER There are several specific problems associated with having a diagnosis of bipolar disorder for which CBT approaches combined with medication are particularly helpful. First, particular techniques from CBT are useful when patients dwell on aspects of the diagnosis not with distorted thinking, but with thoughts that stem from the very real problems associated with the illness. In addition, the beliefs patients have about their illness can be inaccurate and present problems in their management and recovery. These beliefs must be evaluated and made more functional and realistic whenever possible. Interpersonal and social issues must be a focus of attention in therapy, either

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with problem-solving or skills training. Suicide is a real threat when patients have bipolar disorder, and specific CBT approaches to the management of the suicidal bipolar patient must be employed. Manic episodes and rapid cycling are often challenging clinical problems that require patience and skill. Finally, adherence to medication treatment is often a substantial challenge in the care of bipolar patients. Specific CBT approaches to use in combination with medication have a substantial evidence base to improve adherence here, resulting in the prevention of hospitalization and decreasing episodes of mood instability.

Cognitions About the Diagnosis of Bipolar Disorder That Are True and Not Useful The day-to-day reality of integrating a new diagnosis of bipolar disorder into one’s life is an enormous challenge. Frequently, the patient is a young adult who must cope with having a serious and chronic illness that will likely require particular modification and restriction of her future life goals and daily behavior. Imagine what a disruption the need for regular sleep hours creates in the life of a typical college student who must contend with the onset of this illness. Particular career aspirations must be reconsidered and sometimes discarded. The dilemma of what to tell and when to tell other people is real and can incur losses—often at a time of life when confidence about interpersonal relationships and personal attractiveness is not at its peak. Grief and anger often occupy the patient after the initial diagnosis. Patients frequently identify thoughts such as, “It is not fair that I have this!” And they are right. Good therapy will make room for these thoughts and emotions. The next therapeutic task is to help the patient realistically modify his expectations and identify and work toward new goals that are within his grasp. Another “loss” that patients frequently mourn is the “loss” of the manic state—or at least the part of the manic state that occurs before control is lost. One way to help a patient deal with mourning this loss is to identify the parts of this state of mind that are not so pleasant. Another important technique is to validate the sadness the patient feels and what realistic losses exist (e.g., the aspects of the manic state that the patient valued—increased energy, inflated self-concept, and so forth), while at the same time acknowledging the real costs this state of mind incurred. It is important for the clinician reviewing the pros and cons of the manic state to have a clear and specific plan to enumerate the costs, because the patient may have a more vivid and positive memory of

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his high mood state. A good illustration of this is a conversation that Carol had with her therapist about sleep habit management. Carol: I just can’t seem to get myself together to try and sleep by midnight. So much of the good work I’ve done in the past has been “burning the midnight oil.” And it takes me such a long time just to get myself together to get started. Therapist: That’s a habit you’ve had for a long while, I know. Remember how we looked at the results of poor sleep? Carol: I know, I know. But it doesn’t seem reasonable that I need to be so strict with myself. And after the last hospitalization I need to make up for lost time. Therapist: You are remembering correctly—there certainly were times when you got things done while staying up late. But then what happened? Carol: Well, I got myself out of control. When I am at my peak, working on all burners, it just feels so good. I keep wishing I could find a way to just keep it at that level and not go overboard. Therapist: That certainly makes sense. But what do you know about how realistic that is? Carol: It’s been a disaster the last three times. Even though I think I’ve managed to control it. It’s not like when I was younger. Therapist: So we need to find a way for you to change the idea that you need to make up for your time in the hospital and that the best way to do that is to stay up late, okay? A different set of realistic negative thoughts that patients have stems from the need to cope with actual side effects of medication that are at the least unpleasant, and at worst a source of significant health risks. Current medications commonly used for bipolar disorder can produce other chronic medical problems (e.g., weight gain, hyperlipidemia, and diabetes with secondgeneration antipsychotic medications). Best practices in collaborative treatment entail each provider making a thorough assessment of the patient’s response to her particular side effects and then making as much effort as possible to find solutions to them that are acceptable to the patient. Perfect outcomes here are genuinely the enemy of good ones. There are times when it is necessary to accept a compromise in order to gain the patient’s acceptance of medication treatment. A particular trap that some medication providers fall into is to tell

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the patient that there were times in the past when medication side effects were even worse and the patient should be grateful about the newer agents available. This line of discussion is not helpful and can derail adherence. It can be quite helpful to describe how in the future, it is highly likely that there will be other, better medications available with fewer side effects and to present the history of medication management of bipolar disorder as evidence for optimism.

Distorted Cognitions About Having Bipolar Disorder Of course, not all the thoughts a given patient has about living with a diagnosis of bipolar disorder are accurate. Each of us has particular personal meanings about any illness that can be “roadblocks” as treatment proceeds. Typical distorted thoughts about bipolar disorder can be about the mental illness itself—many patients have internalized cultural prejudices about mental illness that are inaccurate that further damage their self-regard. These beliefs can cause even more difficulty with acceptance of treatment. Some patients deny (or have family members who deny) the existence of mental illness at all—these patients often will say that the diagnosis is an “excuse” and that they just need to “try harder.” Bipolar disorder is so pervasively identified as a “biological” illness that it is sometimes difficult to enlist patients in the work of changing life habits, because they believe that all they need to do to stay well is to take medication. Such patients may have thoughts like, “There’s nothing I can do about it; it’s my chemistry.” When a patient has these beliefs and becomes depressed, it is quite difficult to enlist them in the work of behavioral activation without uncovering and challenging this thinking. Other beliefs that can interfere with patient management include beliefs about psychotropic medication that can interfere with adherence. Often, such beliefs have their foundation in the patient’s ideas about the relationship between bipolar disorder and creativity or productivity—for example, “I can’t write while I am taking lithium—it dulls my brain.” Clinicians working with such patients must walk a fine line by acknowledging that although it is true that the medications prescribed to regulate mood have cognitive side effects, the consequences of episodes of mania and depression with respect to productivity are far more dire. Jamison and colleagues (Jamison, Gerner, & Goodwin, 1979) surveyed patients about the reasons for medication discontinuation soon after the mood-stabilizing properties of lithium were discovered. Their work contained the surprising

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finding that the most important reason given by patients for medication discontinuation was the patients’ discomfort about the fact that their mood was controlled by medication. This is a belief that is helpful to uncover and discuss. However, patients who have had severe and frightening affective symptoms can develop hypervigilance and fearfulness about any alteration in mood state, and restrict their lives so significantly that it can contribute to depressive symptoms. Carol, the patient we have followed through this chapter, is a good example of such a patient. Carol came into treatment because of an exacerbation of depression. When her therapist asked her how she spent her time each day, Carol answered that she went to work and then came home to her apartment and followed the same routine every day. She would fix her dinner, tidy her apartment, read a magazine, shower, and go to bed after taking her medication. On the weekends, she would see her cousin at church on Sunday. She would do a few chores, but would never go to the movies or out to hear music—even though previously, these activities had been very important to her. Her therapist asked her why she had stopped doing these pleasurable things; Carol responded that she was afraid that they would contribute to her becoming “too interested in something” and increase her mood state too much. The therapist worked with Carol to design behavioral experiments about a “dose” of enjoyable activity that she could try early in the day to see what happened to her mood. They gradually built several low-key pleasurable activities into each day, and Carol’s mood improved.

Interpersonal and Social Issues Patients with bipolar disorder face special interpersonal and social challenges, in addition to the developmental delays previously mentioned and the daunting task of managing their mood episodes. First, acute episodes of mania or depression exact a high price interpersonally and socially. Patients frequently spend a great deal of time and energy attempting to repair the damage from a significant depressive or manic episode. Jobs are lost, academic progress is derailed, relationships end, legal and financial consequences mount, and health and well-being suffer. Family and friends can experience caregiver burnout and abandon the patient. Resources for patients with severe mental illness are few. These losses are particularly painful for patients who have had hopes and aspirations for a different life trajectory that is now no longer easily available to them—if available at all. Therapy must support the patient’s efforts to repair

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his life and to use his strengths to develop a plan for meaningful work and solid relationships. A common trigger for mood episodes can be relationship strife. Family relationships can be a source of stress that derails a patient’s progress, particularly when families have high degrees of expressed emotion or criticism. Families and significant others who blame the patient for her symptoms and who are intrusive and critical regarding medication adherence are particularly problematic. Therapy must include a thorough assessment of the patient’s interpersonal supports and, whenever possible, education of family and significant others. When Carol struggled with relationships, it had a detrimental effect on her progress. Carol had one significant relationship with a man when she was in her 20s. She met him at her after-care program following a hospitalization. He had a history of cocaine dependence and depression. In the eight months that they dated, he was often verbally abusive to Carol, and he demanded money from her whenever she got paid. If Carol would object, he would tell her she was crazy and that no one would be interested in having a relationship with someone as sick as she was. Carol’s parents were also constantly criticizing her and told her that if she took medication it meant that she was weak. Whenever Carol and her boyfriend had arguments, he would ask her if she had been taking her medication and tell her that she was “out of her mind” when she would try to stand up to him. Carol had three hospitalizations in the eight months that they were together—each time after she discontinued medication following a significant argument with her boyfriend. Carol believed that this was the only relationship that she would ever have because of her illness. Finally, patients who are bipolar face particular challenges with respect to finding a life partner and in deciding whether or not to have children. Women with bipolar disorder face multiple problems when they elect to bear children—these include the question of possibly transmitting the disorder to their offspring (a concern of men with bipolar disorder, also); the difficulties with having a normal pregnancy because of the teratogenic potential of many of the drugs used to attain mood stability; the potential to induce mood cycles or to change the form of the disorder to more malignant rapid cycling when medication is stopped in an effort to become pregnant; the increase in cycles that is possible because of the effects of estrogen and progesterone during pregnancy and postpartum; the higher risk of postpartum psychosis; and, finally, the significant self-doubt that could occur about the ability to be a normal parent based on having the illness. Additionally, managing the life

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stress of a new infant, particularly since sleep deprivation is so provocative for mania, is a daunting task for a woman with this illness. Breastfeeding is another hurdle because of the concentration of medications in breast milk. Childbearing is a prime example of a situation that challenges bipolar patients and their care providers—both accurate, existential issues and idiosyncratic personal meanings can be part of the patients’ thoughts and reactions to what is normally a positively anticipated part of adult life. It is important to examine your own beliefs as a caregiver to a bipolar patient who desires to conceive. Frequently, care providers and others make negative judgments about patients with chronic psychiatric illness who want to have children that they would not make about patients with a chronic medical illness (e.g., multiple sclerosis or diabetes mellitus) that is adversely impacted by pregnancy when such patients desire to become pregnant (Burt, Bernstein, Rosenstein, & Altshuler, 2010).

Suicide in Bipolar Disorder Bipolar patients have one of the highest risks of suicide in any psychiatric disorder. Fifteen to 20% of patients with the disorder will die by suicide, and patients who are bipolar have a higher degree of lethality when they make suicide attempts than patients with other mental disorders (Baldessarini et al., 2006). One reason for the increase in suicide rates may be that the amount of time spent in the depressed phase is considerably greater for bipolar patients. Antidepressant medications do not work for bipolar patients at a significantly higher frequency compared to patients with unipolar depression; therefore, the burden of low mood unrelieved by medication is far greater. Furthermore, combining CBT with medications could be a powerful force in working to manage the distorted thinking of depression when medications are less effective. Clinicians working with patients with bipolar disorder must teach them to actively and directly examine their thinking so that the skill to do this is well learned and can be employed when mood symptoms occur. An advantage of medication with respect to suicide is that patients who are on lithium to manage their mood instability have a lower risk of suicide relative to other mood stabilizers; such patients have an acutely increased risk for suicide when they discontinue lithium, particularly when they do so abruptly (Tondo, Hennen, & Baldessarini, 2001). A second factor that may accelerate the risk of suicide is that bipolar patients incur major psychosocial consequences from mood episodes and often must rebuild a life again and again; often, social supports become alienated and

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resources are few. The patient faces the increased burden of both the mood state and the interpersonal consequences of the mood state. Because bipolar patients have such a significant risk of death by suicide, it is critical for everyone involved in treating and supporting them to maintain a high level of awareness of the risk. Clinicians must ask directly and specifically about the patient’s desire to kill himself and about access to particular means (most importantly, about access to weapons), and then must work with the patient to actively enumerate the reasons for living and dying when suicidal thinking is present. Therapists must be active and collaborative with the patient in looking at the “downside” of suicide and in helping the patient develop resistance to the idea by increasing his understanding of his strengths and the supports available to him. A critical strength to develop in bipolar patients who are at risk for suicide is to help them learn to delay impulses—in particular, to delay action when suicidal thinking is present. Patients who are bipolar must have engagement with meaningful pursuits, life goals, and interpersonal connections. Clinicians who work with them must be proactive in helping the patient develop solid interpersonal connections. Patients who are bipolar may have significant skill deficits with respect to the capacity to solve problems, particularly interpersonal problems. This skill deficit has been identified as a frequent impairment in patients with suicidal behavior (McAuliffe et al., 2006). Therapy must actively and directly address learning to resolve interpersonal conflicts, and help the patient learn how to generate and evaluate solutions. A third issue related to suicide is co-morbid substance abuse and dependence. In patients with both problems, suicide attempts are more frequent (Levin & Hennessey, 2004), particularly when the patient has Bipolar I mood disorder (Sublette et al., 2009). Clinicians working with bipolar patients can enhance adherence, decrease mood episodes, and decrease suicide attempts by carefully assessing and specifically targeting substance use. Self-report and collateral information about substances should be obtained routinely, and both problems must be addressed when present. Motivational interviewing (to enhance willingness to decrease use), harm-reduction strategies, dual-diagnosis group therapy, and 12-step programs can supplement cognitive and behavioral strategies that impact both conditions.

Managing Manic Episodes Manic episodes are some of the most dramatic and dangerous manifestations of mental illness. Behavioral strategies and adjunctive pharmacotherapy can

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be effective at forestalling or attenuating mania if patients are capable of recognizing symptoms in time. Adequate time and attention must be paid to teaching the patient how to recognize and respond to prodromal symptoms of mania during periods of normal mood. An early treatment goal is to persuade the patient of the importance of controlling manic symptoms. The use of an advantage/disadvantage analysis of being in the manic state, and the development of a record the patient believes about what happens when he is in prodromal, early, and full-blown episodes of mania, are very important tools to employ. In dual responsibility therapy, a call to the prescribing clinician is indicated when manic symptoms begin—medication use can be invaluable to increase sleep in the prodromal phase of mania, and medication can decrease any hyperactivity and psychotic thinking if symptoms are more severe. Patients who are developing manic symptoms must be seen and spoken to more frequently—another advantage of collaborative care. Monitoring for substance misuse, helping the patient decrease behavioral and interpersonal stimuli and stress, and re-establishing a regular sleep/wake cycle are of paramount importance. The patient’s social supports must be contacted and a “full court press” instituted to prevent impulsive and reckless behaviors— specifically those involving money, driving, or sexual activity. Cognitivebehavioral treatment manuals (Newman et al., 2001) contain a number of wonderful strategies to discuss and agree to with patients when they are euthymic that the patients can employ when mania ensues—for example, the “two-person feedback rule” (when the patient must check with two trusted friends to see if a perspective or decision makes sense before acting on it) and the “48-hour rule” (the patient must wait 48 hours—2 full days—and get 2 full nights of sleep before acting on any decision). These agreements, when they are in place before a manic mood shift, can be remarkably useful in stopping or at least diminishing the psychosocial damage of a manic episode. Collateral information is of paramount importance whenever a patient is hypomanic or manic, particularly with respect to any history of aggressive behavior and regarding the availability of weapons. One very important intervention to use when working with bipolar patients is to be certain to be clear, with the patient and yourself, that there are limits to the capacity of therapy and medication to stop every episode of mania. Patients are often extremely ashamed and think they or their treatment has failed when they work hard

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to avoid relapse and are unsuccessful. Shame further fuels depression and deactivates future efforts at relapse prevention. Each stumble is an opportunity to learn more about the patient’s illness and rework the plan.

Specific Strategies That Treat Rapid-Cycling Bipolar Disorder Skill and persistence must be employed when working with bipolar patients who have a more challenging form of the disorder—rapid-cycling bipolar disorder. This form of bipolar disorder is defined by the patient having four episodes of mood disruption in 12 months. Reilly-Harrington and Knauz (2005) have developed a particular treatment protocol for these patients, who are known to be particularly refractory to antidepressants and who have significant life disruption because of their mood states. This protocol asks the therapist and patient to be particularly diligent about daily mood graphing and then to carefully employ problem-solving in an anticipatory way so as to make episodic disruptions milder and more manageable. Every subtle shift that occurs in the patient’s mood, particularly as mania or hypomania begins, must be aggressively targeted. When a patient has this form of bipolar disorder, it is an instance when a nonpsychiatric therapist must know medications well enough to be aware of what agents might help the patient and have a rapid and reliable means of communication with the medication provider. In rapid-cycling bipolar disorder, all members of the patient care team must aggressively target regular sleep as a goal. Any decrease in sleep duration must be treated pharmacologically and behaviorally. In addition, adding cognitive behavioral strategies is even more important to help patients with the rapid-cycling form of the illness when they develop depression. Pharmacotherapy for depression in such patients is of limited usefulness. Some data point to antidepressants of certain types (specifically, tricyclic antidepressants and SNRI/SSRI antidepressants) as accelerators of cycle frequency, but this has yet to be clearly determined (Licht, Gijsman, Nolen, & Angst, 2008). Antidepressants are also not reliable agents to relieve depression symptoms in rapid-cycling patients. Therefore, any behavioral strategies employed when depression begins can have a powerful function by helping the patient continue to maintain engagement with positive and purposeful activities. Cognitive strategies can help patients to reevaluate negative cognitions and be less subject to the negative biases that may be initiated by disappointing and adverse life events.

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Medication Adherence in Bipolar Disorder No chapter on treating bipolar disorder would be complete without a discussion of treatment adherence. The combination of CBT and medication conveys a particular advantage regarding adherence in bipolar patients. Estimates of nonadherence in bipolar patients are that one in three persons with the problem fails to take at least 30% of the medication prescribed (Scott & Pope, 2002). Medication adherence is a top priority because of the dangers of relapse, the possibility of shifting the patient into a more malignant form of the disorder, the possibility of suicide, and the psychosocial and interpersonal damage that may ensue with another episode. Patient beliefs affecting adherence and strategies for countering these beliefs have been discussed in Chapter 4. All of the weapons that exist in the arsenal of cognitive and behavioral strategies to enhance adherence must be available to a clinician managing an instance of nonadherence in a bipolar patient. A fundamental problem involved in the requirement to take medication for any chronic illness is that there are few obvious sources of reinforcement for taking medications on a daily basis when one feels well. Compounding this is that many of the medications we prescribe for bipolar disorder have adverse side effects. Clinicians need to be consistent and repetitive in educating the patient about the rationale for medications. When the patient is in dualresponsibility treatment, everyone involved in the patient’s care must make assistance with medication side effects a main concern. Both the medication provider and the nonpsychiatric therapist in this model should put adherence on the agenda at each session. Homework assignments about medication should be a part of therapy and medication management sessions. Because there are such significant attention and memory problems associated with bipolar disorder, patients need to be reminded verbally and in writing of the reasons they must be consistent and predictable with medication. Family members and significant others must be included in the effort to ensure that medication is taken regularly and must be aware that adherence is of paramount importance. Everyone supporting the patient must remember how difficult it is to manage often complicated pharmacotherapy regimens under calm and predictable circumstances, let alone when life is erratic or when there are difficult life events. The goal is to reduce nonadherence as much as possible, avoid power struggles about medication, and foster diligent and methodical investigation and problem-solving to manage side effects.

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Obviously, a good therapeutic alliance enhances and promotes adherence. Whether a single practitioner is responsible for the patient, or the patient is under the care of two providers, careful attention to the quality of the relationship(s) is vital to patient management. The more that therapists and prescribers share a common language and model for enhancing adherence, the greater the reinforcement of concepts and key strategies for the patient. When the patient’s needs as a person are acknowledged and conceptualized by the team, adherence is easier to attain. The challenges that we face in treating patients with bipolar disorder are substantial. Collaborative treatment or combined evidence-based psychotherapy and pharmacotherapy with a single provider can improve patient outcomes and increase psychosocial function.

Combining CBT and Medication: An Evidence-Based Approach by Donna M. Sudak Copyright © 2011 John Wiley & Sons, Inc.

CHAPTER

7 Combined Treatment for Anxiety Disorders OVERVIEW Anxiety disorders are some of the most prevalent and disabling psychiatric conditions. Unfortunately, it is not easy to determine whether single or combined treatment is the best method to recommend to the patient with anxiety. Studies of single versus combined treatments are small and often compare different types of medications combined with CBT administered in varying formats. Additionally, there is little evidence about how to best approach patients with anxiety who have co-morbid conditions, which is typical in clinical practice. This chapter will review existing studies that combine CBT with medication for specific anxiety disorders and describe an approach to integrating the two modalities. Because of the number of diagnoses in the anxiety spectrum and the paucity of specific information about combined treatment, the chapter starts with general principles that facilitate collaborative care in treatment for anxiety and then reviews the evidence about using medications with CBT in panic disorder, social anxiety disorder, obsessive compulsive disorder, and posttraumatic stress disorder. These four disorders have the most data available about combined treatment.

PRINCIPLES THAT FACILITATE DUAL RESPONSIBILITY TREATMENT IN ANXIETY DISORDERS To collaborate in optimal treatment of a patient with anxiety using CBT and medication, practitioners need to agree about several key theoretical principles. 103

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If these are in conflict, the patient will be confused at best; at worst, treatment efforts will fail.

Anxiety Cannot Be Eradicated Patients who suffer with anxiety want it to vanish from their lives. They want to never experience the physical sensations and psychic pain of anxiety again. They quickly learn to avoid any stimuli associated with anxiety. Relief is their goal. Practitioners working with such patients need to clearly communicate that anxiety is good. It is a protective, genetically preprogrammed emotion that facilitates survival. Patients with anxiety almost never consider this fact, and see the symptoms they have as entirely pathological or dangerous. A central tenet of CBT treatment is that anxiety is normal and protective. Successful treatment of anxiety disorders occurs by employing patient education, coping strategies, exposure, and cognitive remediation. Therefore, patients need to understand the physiologic mechanisms that underlie anxiety to cope with symptoms and restructure dysfunctional cognitions. The “vicious cycle” that occurs when patients have catastrophic beliefs about their anxiety needs to be described. Additionally, patients must learn that anxiety symptoms normally wax and wane—and that each time symptoms recur, there is an opportunity for practice and exposure. This fact can help patients stop equating a recurrence of anxiety symptoms with the idea that treatment has “failed.” In dual responsibility treatment, differences such as a practitioner who has an understanding of anxiety as a manifestation of deep intrapsychic conflicts working with a medication provider who uses CBT, or a medication provider who believes that medication must be given to eradicate all anxiety symptoms working with a therapist who is trying to conduct exposure, can undermine an integrated approach to the problem. A good illustration of how a lack of integrated treatment can impact treatment for anxiety is Robert, a patient with social anxiety disorder and major depression. Robert is a 32-year-old man who lives alone. His life has been severely curtailed by his symptoms; although he is extremely bright, he has not finished college, has few social contacts, and can only manage to work as a dishwasher in a fast-food restaurant. Robert was referred to treatment by his primary care physician. He was given a prescription for sertraline and clonazepam after telling his physician about the depth of his depression during his annual physical exam. Robert only takes the clonazepam prior to going to work. He “saves them” for

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that moment of the day, because for the first time, he has had some relief from the terror of leaving his apartment and the dread of confronting his coworkers and his fear of their disapproval. He is preoccupied with the need to return to his doctor to get a new prescription and concerned that his physician might refuse to renew the clonazepam. Robert’s history is a good example of the hurdles that exist when managing patients who have been medicated for anxiety without the benefits of an integrated approach—he is now most concerned about obtaining more medication to partially relieve his symptoms, and he does not have an understanding of the nature of his problem. Robert also is likely to be confused by the fact that successful treatment will involve experiencing and tolerating his anxiety in a different context, since he just obtained badly needed relief and believes that his anxiety might “go away.”

Patients Must Stop Avoidance Behaviors as Often as Possible Everyone involved in caring for a patient with anxiety must encourage the patient to engage in exposure-based treatment. Exposure is one of the most potent psychological treatments known. Unfortunately, it is underused and inconsistently applied by many practitioners and patients. In combined treatment for anxious patients, joint support of the patients’ efforts to gradually and frequently confront internal and external sources that provoke anxiety is vital to success. Many people intuitively understand the underlying principle of exposure—that is, gradually increasing the difficulty of stimuli confronted and staying in contact with the stimulus until anxiety reduces. If you ask a typical patient with anxiety how one would help someone with a simple phobia, for example, of dogs, most will describe a brief exposure exercise. The principle of confronting feared situations deliberately and mindfully must be repeatedly and clearly communicated to the patient by every treatment provider. The experience of anxiety should be pursued by the patient as a goal. Patients who are engaging in exposure need empathic support and praise for their efforts. Joint treatment works best when each partner inquires as to the nature and extent of exposure practice and then applauds the patient’s efforts. Exposure appears deceptively simple, but it involves creativity, planning, and persistence. Identifying patient predictions about the exercise facilitates cognitive restructuring but is frequently neglected as a part of the process. Exposure exercises must generate symptoms: Items must be sufficiently anxietyprovoking for patients to notice a decrease in emotion as they habituate.

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Items also must entail a desirable enough goal for the patient to endure such discomfort and be of a manageable size. For example, a religious patient with agoraphobia might have an initial target to go to her church for ten minutes on a Sunday afternoon while no one else was there. Because the neural circuitry for fear learning is located in the amygdala, and because it is likely that exposure changes neural pathways in the hippocampus, fear learning is not “undone” by exposure. Patients learn something new about the fear. Therefore, this new learning must occur frequently and in many different contexts. Exposure must be repeated to consolidate learning and make the working memory that the feared stimulus is “safe” automatic. This principle means that items that are assigned are optimally ones that the patient can do again and again. For example, an individual with a flying phobia who masters her fear for a particular occasion and who then does not fly for several years may find that she again has severe anxiety anticipating a second flight. If a person with such fears must fly weekly for her business after treatment, the return of symptoms is far less likely. Patients need to know that relapse prevention involves continual practice.

Patients with Anxiety Can Provoke Symptoms By Just Thinking About Anxious Stimuli Another important concept about anxiety disorders that treatment providers should share is that triggers for patients’ symptoms generalize. Patients can become chronically anxious or worried about future occurrences of anxiety. Frequently, they struggle with symptoms that are generated just by thinking of anxiety-provoking stimuli. Patients can become fearful about situations that “seem” connected to the anxiety. Patients who have had unsuccessful treatment for anxiety and continuous symptoms can benefit from discussing negative expectations about treatment. Often, the life experiences of such patients have taught them “nothing works.” Patients with chronic anxiety often have concerns about being overwhelmed in therapy; they fear “having a nervous breakdown” or “becoming psychotic.” Patient, persistent education is needed to combat these ideas. Empathically acknowledge the discomfort experienced by every anxiety patient. Make certain you ask about avoidance as an impetus for lack of attendance and adherence. Homework must be of a manageable size; ideally, it should be designed with the patient. When we employ tools such as asking the patient to rate her percentage of belief about a particular prediction, such thinking begins to be more abstract and less powerful.

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A good illustration of avoidance of thinking about anxious stimuli is Marie, a patient with severe panic attacks. Marie is a 30-year-old woman with panic disorder and agoraphobia. Her panic disorder is generally precipitated by fears of and/or the sensation of dizziness. Marie avoids thinking about or talking about these episodes because she is afraid if she does so “it will bring it on.” She avoids any activities that have been associated with her dizziness (she never enters an elevator, for example and she avoids being alone whenever possible). Marie believes that talking or thinking about her symptoms will accentuate and worsen them, and that she will “go crazy.” Marie is preoccupied with seeking objects that she can hold on to or sit on should she become dizzy. She avoids turning her head quickly and any sudden changes in position.

Co-Morbidity Is the Rule Rather Than the Exception in Patients With Anxiety Disorders Patients with anxiety disorders are at risk for multiple types of anxiety. For example, patients with panic disorder have an increased risk of agoraphobia. Patients with anxiety disorders have a higher risk of depression, with a lifetime prevalence of 50 to 60% in patients who have panic disorder (Kessler et al., 1998). Patients with anxiety and co-morbid depression are at a higher risk for suicide attempts and completion (Weissman, Klerman, Markowitz, & Ovelette, 1989) than patients with either condition alone. Substance misuse and dependence are frequent, perhaps because patients use them to obtain relief from symptoms or because of a genetic predisposition for both conditions. Co-morbid conditions make treatment more complicated. Anxiety disorders are frequently heterogeneous in their presentation—patients have symptoms that overlap between diagnostic categories and can appear to have more than one type of disorder simultaneously. A good approach is to think about anxiety transdiagnostically, that is, as a process of thought and perception with targets that are misperceived as dangerous that vary from person to person. Co-morbid mental illness, like depression or substance abuse, requires a careful review of which disorder causes the most distress and whether one disorder will prevent successful treatment of the other, in order to determine how to proceed first. The struggle to set priorities in treatment is illustrated by Barbara. Barbara is a 23-year-old woman who has severe obsessive-compulsive disorder and major depression. She has been unable to leave the house for anything

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except very brief trips to the doctor because her fears of contamination are so substantial. She is terrified that she will be unable to adequately wash and that “something terrible will happen.” Barbara has been taking showers that last for three to four hours. She has no energy for any other tasks. As she has become progressively more impaired by her anxiety and depression, she has been neglecting basic self-care: She has not been able to go to the grocery store, she is on administrative leave from work, and she has only been able to get to her clinician’s office because her parents have brought her after a referral from her internist. Barbara meets criteria for both Axis I diagnoses. Her obsessions and compulsions are so pervasive that efforts to institute behavioral activation for depression are likely to be futile. Her depression is so severe that the activities required to employ exposure and response prevention seem insurmountable. She has a prescription for sertraline from her internist, but she has been too anxious to take the medication. Anxiety is a common presentation in primary care (Harman, Rollman, Hanusa, Lenze, & Shear, 2002). Models for implementing elements of CBT in primary care practices exist; they improve outcomes in patients receiving medication from primary care physicians (Roy Byrne et al., 2005). Self-help CBT and computerized CBT can also be implemented in primary care settings and yield better patient outcomes. Co-morbidity when treating anxiety disorders can mean managing co-morbid physical and psychiatric illnesses. Patients with chronic medical illnesses may also have an increased risk for anxiety, depending on the illness. When working in dual responsibility treatment for anxiety disorders in this context, both providers must convey a clear message that the patient’s physical symptoms are quite real but do not always signify that the patient is physically in danger. When patients have physical health issues (e.g., coexisting diabetes mellitus or emphysema) and an anxiety disorder, a team approach is critical. Good communication with the physician managing the patient’s physical illness is essential to ensure which elements of interoceptive exposure can be safely conducted and to help educate the patient about what physical symptoms are signals to seek help. The primary care or specialist care physician is a key component of treatment in this situation and must reinforce the suggestions made in therapy.

Anxiety Limits the Ability to Process Information When anxiety occurs, perception, memory, and thought are impaired. Anxiety narrows the ability to process and retain information. This change in memory

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and heightened attention to threat mean that using thought records alone to combat symptoms may be less effective. Patients may have a difficult time identifying what they are thinking at times of high anxiety. Therapists should attempt to normalize this difficulty with memory and identifying catastrophic cognitions. When patients slow down the process of their anxiety and repeatedly ask themselves standard questions that elicit automatic thoughts (e.g., “What just went through your mind?”), they are more likely to be successful. The reflexive nature of anxious responses makes behavioral experiments and exposure important components of treatment. Because anxiety interferes with learning and memory, education in treatment of anxiety disorders must be repetitive and in small doses—the patient will not remember everything that is said the first time. Written material and repeated discussions are essential.

Lifestyle Management and Relapse Prevention Are Important for Sustained Recovery Whether in single or collaborative treatment, patients who struggle with anxiety disorders must know the effects certain habits have regarding their condition. Substance use (alcohol, nicotine, and stimulants), caffeine use, sleep habits, and exercise all have effects on the patient’s vulnerability to anxiety. Current social mores do not always support healthy life habits. Psychologically vulnerable individuals cannot afford to sustain long work hours without making time for proper self-care, nor can they engage in substance use without risking symptoms or rebound. Patients with anxiety also must learn and practice relapse prevention strategies. Anxiety will reoccur in some form when treatment ends. Patients must not panic when this happens; they must deliberately employ strategies that have worked for them in the past. Each opportunity to practice the techniques learned in therapy and to face fears strengthens recovery.

EVIDENCE FOR COMBINING MEDICATION AND COGNITIVE BEHAVIORAL THERAPY FOR ANXIETY DISORDERS Overview Psychotropic medication and CBT are each effective treatments for anxiety disorders. Each has different long-term outcomes for the patient. Generally, CBT interventions produce more durable results when treatment is withdrawn.

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The use of CBT can assist in tapering medication and provide a more stable and prolonged recovery if medication has been the initial treatment modality (Otto et al., 1993). Combined treatment with CBT and medication has more variable outcomes. First, for most disorders, CBT combined with medication, whether antidepressants or benzodiazepines, has not been found to have an advantage or has been less effective compared to treatment alone at the conclusion of treatment. Second, the combination of the two treatments can be more rapidly effective in many patients than either treatment alone, but the durability of the response to combined treatment is less good than treatment alone. Third, the use of benzodiazepine may attenuate exposure-based treatments (Marks et al., 1993). Benzodiazepines are acutely well tolerated and rapidly effective, but convey a risk for dependence, withdrawal, and other significant side effects, including sedation, cognitive and psychomotor impairment, and rebound anxiety when medication is withdrawn. Another recent review of evidence for and against combined treatment (Zwanzger, Diemer, & Jabs, 2008) takes a more nuanced position. This review suggests future directions for research that are similar to those discussed in Chapter 1; namely, that research that identifies patient characteristics that would help us identify who would be best suited for what type of treatment is the type of research that is most needed. These authors cite the most recent comprehensive reviews and meta-analysis about combined treatment for CBT and medication in anxiety disorders and note that methodological issues make existing studies unreliable because of the lack of significant change in outcome when combining medication and CBT. In addition, they cite that nearly all the meta-analytic studies available have been about panic disorder (seven of eleven total studies); only a few investigate SAD and GAD, and durability is not assessed in any. Of the 11 meta-analytic studies they assessed, 5 said the combination of CBT and medication was superior for acute treatment, 2 said CBT alone was better, 2 said medications alone were superior, and 1 was inconclusive. The authors call for more research and recommend the use of combined treatment in patients with co-morbid disorders or in patients who do not have a response to a single treatment. Anxiety disorders that are accompanied by co-morbid conditions, like depression, may respond differently to combined treatment, but this has yet to be tested. Co-morbid conditions are common in populations with panic disorder. One review cited the average rate of patient acceptance into efficacy trials in anxiety as only 36% because of co-morbid diagnoses (Westen & Morrison, 2001). Certainly

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depression can interfere with the ability to participate in CBT for anxiety. Exposure treatment is demanding, especially in patients with OCD and PTSD, and requires a substantial investment of time and energy from the patient. If co-morbid depression prevents participation in treatment, combined treatment may increase positive outcomes. Conversely, anxiety can interfere with behavioral activation tasks when patients are depressed. Multiple targets of treatment can complicate therapy. If progress does not occur with CBT interventions in patients with significant co-morbidity, careful consideration of pharmacologic treatment is warranted. In addition, some patients are so disabled from their anxiety symptoms that a more rapid response is desirable. Medication may be prescribed first in this circumstance. Barbara, the patient with OCD and depression whom we met earlier in the chapter, is a good example of such a patient. Barbara was taken by her parents to her internist after she was placed on administrative leave from work. She was nearly entirely homebound, and described feeling profoundly depressed, with pervasive anhedonia and insomnia. Her entire focus of attention was to clean herself and her apartment because of her horrible feeling that it was contaminated. She felt that her life was not worth living, although she was terrified of death. She was unable to concentrate to read or watch television, because she would be distracted by the need to wash her hands. Barbara was treated by her internist with sertraline and referred to therapy for her OCD. Combined treatment for anxiety typically occurs when patients are referred by primary care physicians to therapy after they have been given an initial medication for their symptoms. In this circumstance, adding CBT can facilitate medication discontinuation and improve the chance for a full recovery. This sequence of treatment is similar to the treatment employed in major depression, as described in Chapter 5. It allows the patient to first obtain relief from symptoms and then engage in CBT when they may be more capable of remembering the rationale, tools, and new skills to cope. Medications are then discontinued. Thereafter, the patient uses exposure and cognitive restructuring to continue to tackle previously feared situations. Many authors believe that if patients learn CBT skills only when taking medication, the patient’s internal context (the physical feelings the patient has when taking medication) and external context (the act of taking pills) will be altered when pill-taking stops, so that treatment must extend after medication is discontinued or relapse is more likely. Because of this alteration in the

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learning environment, patients benefit by conducting exposure both during and after the taper of medication (Smitts, O’Cleirigh, & Otto, 2006). When patients receiving combined treatment begin to taper medication, whether these are benzodiazepines or antidepressants, it is critical that the taper is accomplished at a very slow rate. Discontinuation symptoms are common when antidepressants are rapidly decreased and can exacerbate anxiety. Rebound anxiety can derail progress. A recent study indicates that the interval until recurrence of panic disorder is far shorter if medication discontinuation is rapid (Baldessarini, Tondo, Ghiani, & Lepri, 2010). Benzodiazepines are notorious for producing rebound anxiety when tapered. The greater the dose and the longer the duration of use of benzodiazepines, the more a longer duration of a taper is beneficial. Patients will also have a sense of greater control and be more able to tolerate medication discontinuation when they are aware that it will happen in a slow and deliberate fashion. Success in tolerating small decrements in dosage is a mastery experience for the patient and facilitates further dose reductions.

Evidence for the Use of Combined Treatment in Panic Disorder Panic disorder is a debilitating illness that adversely affects a patient’s quality of life and productivity because of emotional distress and learned behavioral avoidance. It increases the risk for other mental disorders, such as depression and substance abuse, and conveys an increased risk for death from suicide and cardiovascular disease. Because physical illnesses can mimic panic, it is important that every patient with panic disorder has one thorough health assessment to make certain that no treatable medical condition (hyperthyroidism, for example) is causing the problem before therapy ensues. Panic patients experience their problems as utterly uncontrollable and unpredictable. Panic patients develop a predisposition to a higher degree of apprehensiveness that causes them to be very concerned about the possibility of future attacks (Bouton, Mineka, & Barlow, 2001); in addition, they become exquisitely attuned to physiological sensations that accompany the attack. Panic patients benefit from understanding that they may have a temperamental predisposition to higher anxiety and increased sensitivity to anxiety and physiological sensations. Other problems ensue as patients try to cope with symptoms; either they begin to avoid stimuli associated with their symptoms, or they start to misuse prescription medications or substances in an effort to adapt.

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Studies of benzodiazepines (alprazolam) (Marks et al., 1993) and imipramine (Barlow, Gorman, Shear, & Woods, 2000) combined with CBT show no advantage for combined treatment over treatment alone and less durable treatment responses when treatment ends. Not surprisingly, in the benzodiazepine study cited, the best predictor for relapse was the degree to which responders attributed their success to taking medication (Basoglu et al., 1994). One important criticism of both the Barlow and Marks studies previously referenced is that the nature and dose of the medications used is not typical in current clinical practice—imipramine is rarely prescribed for panic disorder at present, and the dosage of alprazolam used was far higher than generally prescribed and for a short duration. The speed of the medication taper in both studies was much more rapid than most clinicians would recommend in patients with panic disorder. A seven- to fourteen-day taper of medication often produces significant rebound symptoms in such patients, but is typical in research studies. Using benzodiazepines on an as-needed basis and providing CBT may be the worst method of combining treatment because the rapid relief from symptoms that ensues after taking benzodiazepines is a potent reinforcer of medication use and eliminates the chance for exposure and active coping. In addition, there is the aforementioned danger that the patient will attribute successful coping to the use of medication. Therefore, the use of medication to “eliminate” anxiety must be done with care and education because of the contradictory nature of this modality. Pharmacotherapy for panic disorder with no therapy has a higher risk of rebound anxiety when medications are stopped (Pecknold, Swinson, Kuch, & Lewis, 1988) and higher recurrence rates whether medication is discontinued or maintained (Simon et al., 2002). Some authors have suggested that sequential prescription of combined treatment with CBT following an initial prescription of benzodiazepines in panic could both facilitate tapering the drug and decrease relapse rates with therapy by helping patients learn to successfully confront feared situations without using medications (Spiegel & Bruce, 1997). Low potency benzodiazepines do not have as consistently negative an outcome as alprazolam in single studies when combined with CBT, but long-term follow-up of diazepam treatment combined with exposure shows no advantage of the combination (Wardle et al., 1994). In the short term, results vary, but meta-analysis of available studies indicates no advantage for combination treatment. If the combination of benzodiazepines and CBT is the chosen route to manage the patient, a slow and flexible schedule to taper medication with active management of

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patient symptoms is most successful. Good communication between providers is essential, and patients must be encouraged and supported in the effort to taper medication and tolerate discomfort. Patients must consistently remind themselves of the goal ahead and the advantages of stopping medication. An important strategy is to remind the patient that anxiety is uncomfortable, but that it is normal, tolerable, and not dangerous. Patients who believe the treatment procedures in panic disorder make sense are far more likely to comply with and complete the medication taper. Despite the individual studies cited above, a recent review and meta-analysis of studies combining psychotherapy and benzodiazepines (both behavioral and cognitive therapies) for panic disorder indicated that there is inadequate evidence to know for certain that there are benefits or detractions with the combination (Watanabe, Churchill, & Furukawa, 2009). Only three trials were eligible for inclusion in this review. There were insufficient numbers of patients for the analysis to detect statistical differences between the treatments. This systematic review noted that “some observational studies have suggested that benzodiazepines actually interfered with cognitive-behavioral interventions, while others have suggested otherwise.” When the data from the trials included in the meta-analysis was considered, there was no advantage of the combination and a trend toward a disadvantage of the combination in the long term (i.e., six to twelve months). Other risks of benzodiazepine use (dependence, cognitive impairment, injury from falling) must be considered when recommending combined treatment. Another meta-analysis of combined treatment of panic disorder indicates that short-term treatment of panic disorder is most effectively accomplished with antidepressants and in vivo exposure (Van Balkom et al., 1997). This review did not consider durability of response. Still another review found that the combination of antidepressants and exposure is better in longer-term treatment, as well (Bakker et al., 1998). Certainly adding antidepressant medication treatment to CBT is a consideration if there is no response or a suboptimal response to therapy, given the lack of clear evidence. One new application of combined treatment has great promise in augmenting CBT for anxiety; specifically by increasing the effectiveness of exposure-based treatments by combining exposure treatment with the medication D-cycloserine. This method of combined treatment “boosts” the capacity to learn and remember during exposure, rather than treating anxiety itself. D-cycloserine is an antibiotic that is used in complicated urinary tract infections and tuberculosis.

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D-cycloserine is believed to facilitate memory because it is a partial agonist at the N-methyl-D-aspartate (NMDA) glutaminergic receptor. Fear extinction has been linked to these receptors, and these receptors also play a role in the consolidation of short-term learning and memory. Since we assume exposure forms new memories that compete with the fear memory, consolidating memory by adding this medication could enhance outcomes. Animal studies of fear extinction inspired these trials with D-cycloserine (Davis, Ressler, Rothbaum, & Richardson, 2006). Exposure treatment combined with D-cycloserine in small controlled studies of patients with OCD (Wilhelm et al., 2008), social anxiety disorder (Guastella et al., 2008), and panic disorder (Otto et al., 2010) indicate that outcomes can be significantly improved with the combination. This is an exciting application of a tailored combination of interventions that is derived from our increased understanding of fear circuitry and the brain changes that occur during psychotherapy.

Evidence for the Use of Combined Treatment in Social Anxiety Disorder (SAD) A recent placebo-controlled study (Blanco et al., 2010) showed a significant benefit in patients with SAD when combining treatment with cognitive behavioral group treatment (CBGT) for social anxiety and phenylzine, a monoamine oxidase inhibitor antidepressant chosen because it has a long history of documented efficacy in SAD. Patients had superior results with the combination with respect to specific measures of symptom severity in SAD, as well as with response and remission rates, than with either treatment alone. This study cited other relevant combined treatment trials for SAD as well; only one of them used CBT (the other used exposure alone). The other existing trials showed no significant differences between patients in combined treatment with fluoxetine and CBGT and patients in single modality treatment (Davidson et al., 2004). However, at least one study exists that shows no difference between fluoxetine and placebo in patients with SAD who are treated with pharmacotherapy alone (Kobak, Griest, Jefferson, & Katzelnick, 2002), so this combination might not be a good test of effective combined treatment. Blanco and colleagues (2010) reanalyzed the data from a second study, which used sertraline and exposure, and found that there was a gradient of treatment efficacy with combined treatment having the highest rating. Durability was not assessed in any of these combined treatment studies.

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Evidence for the Use of Combined Treatment in Obsessive-Compulsive Disorder (OCD) Combined treatment for OCD is often the treatment given in clinical practice, because symptoms of OCD are so disabling. Patients are frequently reluctant to engage in exposure and ritual prevention treatment without receiving some relief from symptoms with medication. Since a substantial number of patients with OCD continue to have symptoms with either treatment alone, finding a combination that provides better relief would be desirable. Despite this, the evidence for combining CBT with medication as superior to CBT alone for OCD is not clear. One important problem with the data available from controlled trials about whether combined treatment is superior in OCD is that existing studies exclude patients with co-morbid conditions, which are so common in OCD. One study of patients with OCD who were on adequate antidepressant medication, but who had residual symptoms, found that adding exposure and response prevention helped patients moderately reduce these symptoms (Simpson et al., 2008). Many patients with OCD who achieve only a partial response to antidepressants are given antipsychotic agents or an additional antidepressant to see if it will decrease symptoms. Augmentation with CBT has far fewer side effects than an additional medication and may provide patients with coping strategies for symptoms that last longer. CBT has not been directly compared to the addition of antipsychotic medications in OCD patients with residual symptoms who are taking antidepressants. An uncontrolled trial showed that patients with OCD who were treated with antidepressant medications and CBT were not substantially benefited compared to patients who received CBT alone (Franklin, Abramowitz, Bux, Zoellner, & Feeny, 2002). These patients had no co-morbid conditions, such as depression, that could interfere with participating in exposure and response prevention. One important outcome in combined treatment in this trial was that patients who were prescribed SSRI medications and then started CBT had no interference from the medication on the effects of exposure. This outcome can at least give us assurance that we will not sabotage the powerful effects of exposure and response prevention, should we elect to recommend the combination of antidepressants and CBT. Follow-up data about durability was not provided in the study. One review of existing combined treatment trials in OCD indicates that one of four trials clearly showed that combined treatment was better in the acute treatment of the disorder (Black, 2006).

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Evidence for the Use of Combined Treatment in Post-traumatic Stress Disorder (PTSD) Both SSRI antidepressants and CBT have evidence of efficacy in PTSD. Other medications (tricyclic antidepressants, atypical antipsychotic medications, mood stabilizers) have also been tested with some positive results. A recent review of the evidence for combining treatment was conducted to evaluate outcomes in treating PTSD. Only four trials (with a combined total of 124 patients) were of sufficient quality to merit inclusion. No significant differences existed in outcomes in combined versus treatment with either modality alone in this review (Hetrick, Purcell, Garner, & Parslow, 2010). Again, since such meager evidence is available, clinical response may be the only way to help clinicians decide when single or combined treatment is the best recommendation. In summary, there is not clear evidence about what treatment to recommend to an anxious patient. Disorder by disorder, the minimal guidance we have thus far yields the following recommendations: 1. In panic disorder, use CBT alone when it is available and when the patient’s level of severity permits. If combined treatment is provided, use CBT to help the patient discontinue medications and to ensure skill generalization after medication treatment. Taper medication extremely slowly. 2. In SAD, combined treatment may be more effective acutely. There is no clarity about durability. Again, severity and co-morbidity will often be factors that make decision-making clearer. 3. In OCD, patients with severe symptoms or co-morbid psychiatric disorders may only tolerate exposure and response prevention if given medication first. SSRI antidepressants and chlorimipramine are potent fear-reducers that do not interfere with the benefits of exposure and response prevention. 4. Benzodiazepine medications benefits are seldom offset by the risks and rebound symptoms. 5. More data is needed to help us make better recommendations in PTSD.

Combining CBT and Medication: An Evidence-Based Approach by Donna M. Sudak Copyright © 2011 John Wiley & Sons, Inc.

CHAPTER

8 Combined Treatment for Eating Disorders OVERVIEW Disordered eating, whether in the form of binge eating, anorexia nervosa, or bulimia nervosa, presents a challenge to the clinician and is a source of significant morbidity and mortality. Eating disorders are often chronic illnesses— anorexia and bulimia each have significant rates of relapse. Co-morbid psychiatric conditions are the rule, not the exception. Medical complications of eating disorders shorten life and impede physical development. Suicide rates in these patients are high. Clinicians need to make informed, timely decisions about medication use in patients with eating disorders, because there is a high rate of premature termination of treatment, which perpetuates chronic illness. Timing of clinical interventions may influence adherence and outcome. Collaborative care is common in treating most patients with eating disorders. Even if a psychiatrist is prescribing medications and providing therapy, or a nonpsychiatrist therapist is conducting therapy without medication, patients generally require medical monitoring from an internist, pediatrician, or family physician to ensure that they are medically stable and that outpatient treatment is appropriate. Most patients with eating disorders do not develop severe complications, but when medical concerns arise, they can be life-threatening and require coordinated and rapid action. Although eating disorders can be conceptualized transdiagnostically (Fairburn, 2008), this chapter will separate the diagnostic entities, because the research about combined treatment is divided by disorder. Because data about binge eating disorder is limited, the chapter will focus exclusively on anorexia and bulimia nervosa. 119

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EVIDENCE FOR THE USE OF COMBINED TREATMENT WITH CBT AND MEDICATION Evidence for the Use of Combined Treatment in Anorexia Nervosa Data regarding psychotropic medication use in anorexia is scarce. One reason we have such little information about it pertains to the challenge of studying anorexia. It is a relatively rare condition, affecting only 0.5% of women in the United States (Hsu, 1996). Patients with anorexia are often young adolescents, so there is often an ethical concern about their capacity to consent to participate in research projects. Medication may have unexpected effects in younger patients or in starving patients, compared to adults at a normal body weight. Older patients with chronic anorexia have a very high rate of treatment drop-out. In the extremely low-weight patient, participation in research is particularly ethically problematic, because the problem is life-threatening. Critically ill patients are difficult to study because we cannot readily withhold a particular form of treatment that is known to be effective to study another (Halmi, 2008). Psychotropic agents have been studied in anorexia for two purposes: to produce weight gain and to manage co-morbid psychiatric conditions.

Evidence for the Use of Psychotropic Medications to Promote Weight Gain in Anorexia Psychotropic agents that have been used to promote weight gain in anorexia include antidepressants (both tricyclic antidepressants and selective serotonin reuptake inhibitors, or SSRIs) and antipsychotic medications (both neuroleptics and second-generation antipsychotic medications). Antidepressants have not been effective in promoting weight gain, although several studies have determined that they can help patients prevent weight loss once a normal BMI is reestablished (Kaye et al., 2001). Because of the significant side effect profile of the tricylic antidepressants, the use of SSRIs is more desirable and better tolerated. Cyproheptadine is not a psychotropic, but is a potent antihistamine and serotonergic agent. It has been studied as an agent to promote weight gain in inpatients with anorexia. Patients with the nonbulimic subtype of anorexia given very high doses (32 mg) of cyproheptadine had very modest improvement. This dosage is, however, extremely sedating, and therefore is not acceptable

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for most inpatients, and generally for all outpatients (Halmi, Eckert, LaDu, & Cohen, 1986). Neuroleptic agents were initially hoped to hold great promise as an adjunctive treatment of anorexia, because patients have such a degree of thought disturbance about their weight, their eating, and have rigidly held body image distortions. Speaking with a patient who is starving to death but perseverates about how fat she is can be similar to speaking to a patient with a delusion. Unfortunately, early studies of anorexia treated with chlorpromazine did not show that this drug produced any significant benefit with respect to weight restoration or altering patient ideas about weight and body shape. Once second-generation antipsychotic agents were developed and found to have the undesirable side effect of weight gain, there was once again hope that adding these agents would help patients with anorexia. A recent double-blind placebo-controlled study of ten weeks of olanzapine on a flexible dose schedule showed an increase in the rate and amount of weight patients gained and a decrease in obsessional thinking about food (Bissada, Tasca, Barber, & Bradwejn, 2008) when patients were given olanzapine. A nonblinded head-to-head trial of chlorpromazine and olanzapine favored olanzapine as well and enhanced the outcomes of those patients with the binge-purge subtype of anorexia. This randomized pilot study of olanzapine and chlorpromazine also indicated that patients treated with olanzapine had fewer intrusive cognitions about weight and shape (Mondraty et al., 2005). A recent review of 43 studies of atypical antipsychotic medications in anorexia found only 4 randomized-controlled trials. This review concluded that atypical antipsychotic medications do have some effect on depression, anxiety, and core eating disorder thought processes, but also stated that there is not sufficient information to conclude that weight gain in anorexia is affected by second-generation antipsychotic medication (McKnight & Park, 2010).

Evidence for the Use of Medication to Treat Co-Morbid Conditions in Anorexia Nonpsychotropic medications are standard adjunctive treatments in anorexia. It is important to administer estrogen replacement and vitamins to severely underweight women to forestall osteoporosis and vitamin deficiencies. Many patients with anorexia who are in hospital for refeeding are also treated with antiperistaltics to avoid the abdominal discomfort that comes with refeeding

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starved patients and to increase the acceptability of eating. These medications have not been proven to increase weight gain, despite widespread use. Medications can also be effective to manage the considerable psychiatric co-morbidity in patients with anorexia. Psychiatric illnesses are often complicated to diagnose in patients who are quite underweight. Affective symptoms are frequently present in these patients, but distinguishing whether they indicate the presence of a primary depression or are a secondary effect of starvation is a challenge. Most patients with anorexia do present with low self-esteem, problems with sleep, low libido, and feelings of guilt and shame. Many clinicians will attempt to give such patients antidepressant treatment to see if any of these symptoms will improve. Another role of antidepressants in clinical practice is to try to mitigate the significant difficulty patients have with motivation to regain weight. There is likely a benefit to antidepressant medication if affective symptoms have been present during a period of remission of the eating disorder, or if they predate the eating disorder. Other indicators that antidepressants could be helpful include depressive symptoms that have recently increased or increased social isolation, suicidal thoughts or significant negative thinking on the part of the patient that involves more than the patient’s eating, body shape, or weight. Patients who are extremely hopeless about change and who lack motivation for other activities might benefit from a trial of medication as well. Because of the serious nature of anorexia, and because treatment progress can suffer if depression is not managed aggressively, continual assessment for the presence of major depression is important. When patients with anorexia have a clear co-morbid major depression, treating the mood disorder with pharmacotherapy rather than psychotherapy may be more efficient than trying to do CBT for depression while simultaneously treating the eating problem. Patients with anorexia will have cognitive and concentration impairments because of starvation, which will interfere with standard CBT approaches to depression. Therapy time may be best used to focus on the eating problem rather than the depression, since there are not effective biological treatments for anorexia, unlike depression. The relief provided with antidepressants may help the patient concentrate and participate better in therapy that targets weight gain. Fluoxetine has been the most well-researched antidepressant medication used in anorexia with co-morbid depression, and is generally prescribed at somewhat higher than normal doses. Although tricyclic antidepressants were used in the past, there are insufficient benefits to offset the significant problem with side effects from this drug class,

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particularly in patients who have precarious fluid and electrolyte balance and increased cardiovascular irritability. Antidepressants do play a role in anorexia after weight restoration; they may help patients maintain their weight restoration even in the absence of a coexisting acute depression (Kaye et al., 2001). When a co-morbid psychiatric condition other than depression exists and therapy is the preferred method of treatment, it is generally most beneficial to manage problems sequentially, unless the second condition interferes with the treatment of the eating problem. For example, patients with obsessive-compulsive disorder (OCD) independent of the eating disorder may need to wait to work on the OCD symptoms until they are weight-restored. Since diagnosing independent psychiatric conditions in the presence of anorexia is difficult, it is generally prudent to wait for at least several months after the patient attains a stable low BMI (approximately 19) to be absolutely certain of the presence or other psychiatric conditions. It can take 12 to 24 months after a patient is weight-restored to determine a starving patient’s baseline psychiatric status. Finally, clinicians who are treating patients with anorexia need to maintain a high degree of vigilance about the rate of diagnostic crossover to other eating disorders when patients are refed. Many patients with anorexia who begin with a restrictive pattern of eating change to a binge-purge pattern (Strober, Freeman, & Morrell, 1997) and ultimately convert to having bulimia nervosa (Eddy et al., 2008). Patients who are at a very low weight at the start of treatment have a significantly worse outcome and greater vulnerability to relapse (Herzog et al., 1999). The following case example is a good illustration of the problems that are frequently encountered in managing patients with chronic anorexia. Alice is a 35-year-old woman who was referred to treatment by her employee assistance program. She was seen there for “depression,” but the social worker at her company was far more concerned about her chronic mood disturbance, passive suicidal thinking, and lifelong struggle with her weight. Alice was a “chubby” youngster who became obese in later childhood and early adolescence. She describes her high school years as “a living hell” because of her weight. When she went to college, far from home, she became determined to “shed her fat like a cocoon” and developed severe anorexia. She was hospitalized repeatedly throughout her college years, and was often in medical jeopardy because of dehydration and bradycardia. Alice finished college in six years, but did much of her classwork in inpatient psychiatric treatment settings. Alice began purging after normal-sized meals as a means of controlling

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her weight when she was 28. She never binge ate. She said it became “too difficult” then to maintain her weight at 95 pounds by the means of restricting intake, smoking cigarettes, and exercising. She is currently 40 pounds under her ideal weight of 135 pounds. Alice lives alone with her two dogs. Aside from working and going to her health club, she has no social contacts. She sees herself as unsuccessful and unable to “connect” with people and says that she has “missed the boat” with regard to learning to manage relationships and her free time.

Evidence for the Use of Combined Treatment in Bulimia Nervosa There is a larger body of data available to us to consider about combined treatment with CBT and medication for bulimia. Both open trials and randomized controlled trials exist, although there are variations in what outcomes are measured. Some studies focus on abstinence from bulimia as an outcome; others measure a decrease in number of episodes of binging and purging. Durability of response is a variable assessed in some studies, but not others. Antidepressants are the most frequently studied medications used in bulimia. Both tricyclic antidepressants and SSRIs have been evaluated as interventions compared to CBT, and the combination of CBT and medication versus CBT alone or medication alone has been tested (Walsh et al., 1997). Several metaanalyses of the data also exist. These reviews indicate that the combination of medication and CBT is superior, particularly in decreasing binge frequency (Whittal, Agras, & Gould 1999; Bacaltchuk, Hay, & Trefiglio, 2001). There is no difference in efficacy between the antidepressants reviewed (Bacaltchuk, Hay, & Mari, 2000). If combined treatment is acceptable and available as an initial option, it is the most potent acute intervention. Patient characteristics determined by these studies can also guide our thinking with respect to recommending combined treatment versus single treatment in bulimia. Both tricyclic and SSRI antidepressants improve bulimic symptoms whether or not depression is present, generally within eight weeks (Mitchell & Groat, 1984). The higher the frequency of patient purging, the more likely medications will help; the lower weight a patient is, the less likely the medication will be effective (Garner, Olmstead, & Polivy, 1983). One factor that increases response to the combination of treatments is that medications are better tolerated when psychotherapy is added. There is a high degree (up to 40%) of patient dropout with the use of medications alone (Bacaltchuk,

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Trefiglio, deOliveira, Lima, & Mari, 1999). Data from CBT research in bulimic patients can inform our decision about when to combine treatment if it is not the initial choice. A rapid decrease in binging and purging behavior (by 70% or more) by CBT session six or seven has been shown to be predictive of a positive outcome (Wilson, Fairburn, Agras, Walsh, & Kraemer, 2002; Agras et al., 2000). If patients have not had an early decrease in purging and they are in therapy without medication, this lack of progress should trigger a discussion of adding antidepressant treatment as one way to produce a more favorable result. Current practice in medication treatment for patients with bulimia generally is to provide an initial trial of SSRI antidepressants. Tricyclic antidepressants are less well-tolerated by patients and may have dangerous side effects, particularly in patients with precarious fluid and electrolyte balances and increased cardiovascular irritability. These agents are rarely used at present. An additional caution regarding adjunctive antidepressants is that bupropion should not be used with any patient with eating disorders because a higher frequency of seizures occurs in this population with this agent. The mechanism producing the decrease in purging behavior in patients with bulimia given antidepressant treatment is unknown. Patients report decreased hunger and a decreased preoccupation with food when the medication works. Any mood-related binge eating may also improve with antidepressant treatment. The mood stabilizer and antiepileptic drug topirimate has been recently investigated in patients with bulimia. Two randomized controlled trials using topirimate in this population indicate that it has a positive effect in decreasing binging and purging behaviors. Because topirimate has been shown to decrease appetite, it may have further potential to reduce binge frequency (Pope & Hudson, 2004). No other medications have been thus far shown to be effective in decreasing bulimic symptoms. Treatment of bulimia with medication alone has limited durability after medication is discontinued. Of patients in treatment with medications alone, 30 to 45% will relapse four to six months after the drugs are discontinued. Abstinence rates from bulimic symptoms are also low when patients receive medication alone; generally, only about 30% of patients cease binging and purging entirely. The ideal combination of medication and CBT in bulimic patients employs a conceptually driven approach informed by specific patient characteristics that may predict response to treatment. Astute awareness of these types of patient variables can help clinicians recommend combined treatment when

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specific treatment-targets exist that predict a better outcome. For example, CBT would be an important treatment recommendation to patients who have significant dysfunctional beliefs and preoccupation with weight and shape concerns, or to patients who binge and purge at a lower frequency (Garner et al., 1983). Studies of CBT alone indicate that patients gain a small amount of weight, while those patients on medication will lose a small amount of weight (Walsh et al., 1997). If weight loss would make any treatment more acceptable to the patient, then adding medication to CBT may be helpful. CBT likely works to help patients decrease dietary restraint, increase the awareness of and coping strategies for binge triggers, and modify dysfunctional attitudes about food, eating, weight, and shape (Wilson et al., 2002). Patients who only wish to take medication could benefit from some emphasis on these areas of thought and behavior with brief self-help and educational materials provided in medication management sessions. Still other patients with eating disorders are emotionally dysregulated and impulsive, and eating problems function as one way to regulate emotion. At least one study indicates that DBT can regulate binging and purging behavior to a similar degree as CBT for bulimia in this particular population of women (Safer, Telch, & Agras, 2001). Tailoring approaches to the bulimic patient based on the specific conceptualization of patient characteristics is most likely to get the best results.

SPECIAL PROBLEMS IN THE MANAGEMENT OF PATIENTS WITH EATING DISORDERS In addition to the key features of eating disorders—a disturbance in eating habits and a disturbance in self-perception with regard to weight and shape— specific problems often present themselves in working with such patients in dual responsibility treatment. These may include medical problems, poor attendance, nonadherence to homework or treatment recommendations, and complications of co-morbid medical and psychiatric conditions, including Axis II disorders.

Medical Problems and Starvation Eating disorders are associated with physical complications that can be lifethreatening. These may include disturbances of cardiac function and rhythm that could potentially result in irreversible heart damage or death. Common physical problems that occur are the result of starvation, vomiting, and laxative abuse. Obesity is a risk in eating disorders. Everyone involved with the care of

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the patient must be aware of the physical health concerns that exist in these patients and actively collaborate to be certain the patient is safe. Starvation has profound physical and psychological effects. A particular danger of starvation in women with anorexia is that many of them are nutritionally compromised while they are still growing, so they do not attain their expected height. Decreased bone density can occur as a result of malnutrition and cessation of menses, with early onset of osteoporosis. Patients who are starving develop decreased gastrointestinal motility, with subsequent bloating and discomfort after eating. Other physical effects of starvation include cardiac abnormalities, atrophy of the brain, and blood dyscrasias (including decreases in red blood cells and platelets). Starvation causes a predisposition to frequent infections. Because such a wide range of body systems are impacted by severe calorie restriction physical recovery is protracted. The psychological effects of starvation are numerous. Starvation decreases concentration and memory, increases irritability and insomnia, and eventually causes a marked preoccupation with food and eating. Patients often interpret this preoccupation as evidence that their eating could get out of control. Patients benefit from education about the psychological symptoms of anorexia that are related to starvation: Recent findings show starvation and excess exercise can stimulate the reward centers of the brain sufficiently to “addict” the patient to these behaviors (Schneider, 2008). Patients with anorexia also benefit if they know that it may require many months of weight restoration before all the psychological symptoms of starvation disappear. Patients with anorexia (between the ages of 15 and 24) have a twelvefold increase in mortality compared to their peers (Strober, Freeman, & Morrell, 1997). Patients with anorexia are at a higher risk of death than with any other psychiatric disorder (up to 19% when they are untreated)(Andersen, 2007). In addition to death resulting from the risk of medical complications of anorexia, patients with the disorder succumb to suicide at an increased rate. Prescribers and clinicians providing psychotherapy need to be aware of the potential for suicidal thoughts and behavior throughout treatment, particularly when SSRI antidepressant treatment is initiated, given that many patients with anorexia are adolescents and young adults and could have increased suicidal thoughts at the start of SSRI treatment. Techniques to combat suicidal thinking, as described in Chapter 5, are indicated if suicidal thoughts occur. As anorectic patients recover, providers must monitor the patient for known risks, including the development of other eating disturbances, co-morbid psychiatric conditions

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and the risk of suicide. The following patient example is a good illustration of the aftermath of the chronic social isolation, interpersonal skill deficits, and exhaustion from the battle with anorexia. Alice describes having few reasons to prevent her from suicide. She has a long history of passive ideation, but more recently has decided that when her dogs die, she will kill herself. She feels extremely responsible for them. Dr. Field determines that Alice’s dogs are young and healthy. Nevertheless, he puts suicide and life-threatening behaviors at the forefront of the intake session. He determines that there is no immediate risk and engages Alice in making an antisuicide plan. Collaborative treatment is essential when working with patients at an extremely low weight, even when patients are not on medication. Medical consultants must be in communication with mental health professionals working with the patient. It is extremely helpful if part of early treatment involves joint agreement about when hospitalization will be recommended and how frequently laboratory investigations will be conducted and weight will be monitored. The results of weight recording must be clearly communicated to the patient and everyone on the team. Mental health professionals must collaborate with medical consultants to assess the need for hospitalization or more restrictive treatment interventions like partial hospitalization, where supervised eating can occur. Many patients at extremely low weights require supervised eating and nutritional supplementation in order to gain weight, because the number of calories needed to increase weight is so high. Framing this supplementation as “food as medicine” is often helpful. If outpatient care is the chosen treatment, adjunctive nutritional and family support (if the patient is living with her family) will be required if the patient is of very low weight. A good example of the alliance with medical providers is in Dr. Field’s work with Alice. In his initial intake evaluation with Alice, Dr. Field obtained Alice’s consent to speak with her primary care physician. Her physician was enormously relieved that Alice had been referred for mental health treatment because she had been unable to get Alice’s consent to more aggressively manage her eating problem. She had been concerned about Alice’s weight for months. She agreed to be a partner with Dr. Field in Alice’s care and to fax results of Alice’s weight, blood pressure, and potassium blood level weekly, along with any other pertinent physical findings or changes. Dr. Field recognized the alliance with Alice’s primary care physician was the easy part. The harder work involved negotiating a treatment alliance with

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Alice, and helping her to envision a life worth living in the absence of her eating disorder. Over two sessions, he used motivational enhancement techniques with Alice to assess her personal goals and values and the relationship these had to her eating disorder. Medical problems related to bulimia are generally a result of purging. Vomiting and laxative abuse produce significant disturbances in electrolyte balance. This can result in heart rhythm disturbances, and the most severe consequence of these rhythmic disturbances is myocardial infarction or death. Ipecac use is another cause of irreversible damage to the heart muscle. Repeated vomiting can cause esophageal tears or ruptures, which can be fatal. Aspiration pneumonia is another potentially fatal complication of repeated vomiting. Dental enamel can be permanently damaged by repeated vomiting. If laxative abuse is the patient’s preferred method of purging, it can cause fecal incontinence and chronic constipation. Bulimic patients require hospitalization when electrolyte disturbances are life-threatening (e.g., low potassium) or if dehydration causes severe orthostatic hypotension. Weight and electrolyte monitoring must be conducted in a regular and systematic way and the results rapidly disseminated to the patient’s care team. This degree of transparency within the patient’s health care team is essential to make certain that the patient is not in jeopardy. When collaborating with a primary care physician, make certain that the physician knows what you need him to monitor at each patient visit and what and how to communicate to you. For example, orthostatic blood pressure measurement is not a routine procedure at most patient visits, but it is a vital piece of data in anorectic and bulimic patients to monitor hydration. Pertinent historical data (e.g., when the patient reports that she is fainting) is also critical to convey, as is any laboratory value that is abnormal. Fax or secured e-mail communication (in accordance with state and federal law regarding patient confidentiality) of this information to the mental health provider’s office is an efficient means of updating the team. A fax template can be devised and provided to the primary care physician that can be modified as needed, as shown in Table 8.1.

Poor Attendance and Nonadherence Treatment dropout is a significant complication of eating disorders. High attrition occurs from psychotherapy and pharmacotherapy. Many patients with eating disorders refuse to even begin treatment. In one study, patients in combined treatment had a 46% overall dropout rate, and over 5 weeks only 56% of patients

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Combined Treatment for Eating Disorders Table 8.1 Office Visit Patient: Emily Jones

Date: 9/15/2010

New Historical Data: Lightheaded after exercise, no fainting. Gymnastics starts next week Physical Findings: Weight: 94 lbs in gown BMI: 19 BP: 90/50 supine, 80/48 seated, 80/48 standing Serum K: 3.9 Current medications: Ethinyl estradiol and norethindrone (birth control) Multivitamins Next Visit: 9/29/10 Fax to: Dr. Smith xxx-xxx-xxxx Dr. Jones xxx-xxx-xxxx

who began medication treatment remained on medication (Halmi, 2008). In another series, only 30% of patients with anorexia completed treatment (McIntosh et al., 2005). Practitioners can have a far greater impact on the lives of such patients if they target attendance, lateness, and adherence early. In collaborative treatment, prescribers and therapists can facilitate attendance conjointly, and place adherence to the other treatment modality and barriers to attendance on each session agenda. Poor attendance should be explicitly discussed and problem-solved in psychotherapy and pharmacotherapy. Bulimic patients should be directly informed that the reason to vigorously pursue remission early is that it predicts full recovery. Why do patients with eating disorders drop out of treatment so frequently? At the start of therapy, patients with eating disorders may have poor motivation for treatment. Carefully employing motivational interviewing strategies, enlisting family support, providing psychoeducation, and obtaining a specific commitment from the patient to participate in therapy can be helpful initial strategies to support attendance. Patients who have severe Axis I disorders may need treatment for these problems before they are able to fully participate in treatment for the eating problem. Patients who are impulsive may need active problem-solving to mitigate the chaos in their lives, which can prevent focused participation in eating disorder treatment. Patients will not make

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progress when they miss sessions or session time or do not follow through with the tasks of therapy. A good example of a technique to increase a patient’s motivation for treatment is illustrated in this transcript of Alice working with Dr. Field. Alice initially denied wanting to work on any weight-related issues in therapy. Her goal was to feel less depressed. Education about her weight and its relationship to her mood was not successful to motivate her to consider working on the eating disorder. Dr. Field decided to see if Alice’s motivation might benefit from exploration of the pros and cons of her eating problem. Dr. Field: Alice, you’ve told me that part of the problem with your mood is that you have had so few relationships and you aren’t so comfortable with other people. Alice: Yes. I am alone all the time outside of work. I just don’t seem to have anything in common with anyone. It just feels too difficult to know where to start trying to explain myself to anyone. I’ve got so much baggage. Dr. Field: I can see how it could feel like no one could relate to what you’ve been through. I wonder, though, if you’d ever thought about the benefits the anorexia has related to your inability to make connections. Alice: Benefits? Dr. Field: Yes. I know that seems surprising. But the fact is most things that we do have both positive and negative consequences—sometimes ones we aren’t aware of. And my experience is that looking at both sides can sometimes change a person’s point of view about what they are doing. You and I both have agreed to “table” the issue of your eating problem for awhile while we try and see what else we can do to help you to have a happier life. But we might need to look at the anorexia and how it helps or hurts your having that life. Alice: I’m not sure how to do that. It’s just me. I don’t see it being any other way. Dr. Field: Sure. It’s been a part of your life for a long time. For right now, though, maybe we can start to think about the benefits and negative consequences of the anorexia and have you continue that at home.

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Alice and Dr. Field started a list together. Benefits of Anorexia

Problems due to Anorexia

Feel like I'm in control

People avoid me

Familiar way to live

Isolation

Don't need to try new things

Need to smoke

Adding to this list became Alice’s homework assignment. The exercise led her to begin to consider the wider effects of the anorexia in her life and furthered her motivation to consider changing her behavior. Patients with eating disorders have two types of nonadherence— nonadherence to pharmacological treatments (which can be targeted with the strategies detailed in Chapter 4) and nonadherence to the tasks of therapy. A specific tool to decrease dropout rates in patients in medication treatment alone is to add psychotherapy. Another specific etiology of nonadherence to medication treatment is that patients with eating disorders can be extremely sensitive to medication side effects and quite attuned to their physiology. Because of this sensitivity, careful discussion and management of any side effects, combined with gradual and small dose increases, can facilitate the medication acceptability. Nonadherence to the tasks of therapy can be a function of the severity of the disorder. When patients are struggling with high rates of purging, or are too starved to process information and are unresponsive to outpatient psychotherapy, a more intensive level of care may be in order. In psychotherapy, fear of criticism or shame about revealing disordered eating behaviors may also contribute to nonadherence and poor attendance. Education and normalization can help patients if this is a factor. Therapy that teaches patients it is common to experience a sense of distress when they discuss such disturbed patterns of eating may be more successful. Specific interventions that target shame (such as those elaborated in dialectical behavior therapy, for example) are helpful to facilitate attendance and adherence.

Co-Morbid Medical and Psychiatric Conditions Many studies have shown that patients with anorexia and bulimia have a significant number of co-morbid psychiatric symptoms and conditions. In addition to other psychiatric diagnoses, recent work indicates that shame and

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emotion regulation problems are some of the mediating factors that predict eating disorder pathology in some patients (Gupta, Rosenthal, Mancini, Cheavens, & Lynch, 2008). Shame and affective dysregulation can also produce nonadherence to the tasks of therapy and contribute to poor attendance (as indicated above). Eating problems are common in other psychiatric conditions characterized by a high degree of shame and emotion dysregulation—for example, in borderline personality disorder there is a twentyfold increase in risk for anorexia and bulimia, and a tenfold increase in risk for eating disorder not otherwise specified (Zanarini, Reichman, Frankenburg, Reich, & Fitzmaurice, 2010). Axis II co-morbidity worsens the prognosis of bulimia and anorexia. When shame and emotional dysregulation exists, the patient’s treatment plan must incorporate skills training and exposure to difficult emotional states. A common problem in working with patients with emotional dysregulation and eating problems is that the emotion regulation function of eating disorders may be overlooked by practitioners. When patients have more severe Axis II issues, the eating disorder pathology can be placed “on the back burner” or not conceptualized as part of the big picture—that is, as an additional effort to regulate emotion. If everyone caring for the patient does not share this conceptualization, the eating disorder pathology can be minimized. Since patients also often wish to conceal or minimize eating disorders, this omission can be particularly problematic. Don’t forget that other professionals who work with the patient also are generally acculturated to have values that extol the virtues of an unrealistic body shape and weight. This can lead to “blind spots” and minimizing the patient’s problems. The following case example illustrates a typical patient who presents with eating problems that co-occur with difficulties with emotion regulation. The therapist uses harm-reduction as an initial strategy to engage the patient in decreasing her maladaptive eating behaviors. Diana is 24 years old and a senior in college. She came to treatment after breaking up with her boyfriend of five months. She described a history of many tempestuous relationships and a tendency to be “moody and difficult” in her romantic life. Diana drinks to excess two or three nights a week. She says her weight has always been a problem, but she controls it by using laxatives two to three times per week and by vomiting if she eats “bad stuff” or “too much.” On occasion, when she is angry with her boyfriend, Diana will “eat like a locust,” by which she means emptying all the boxes of crackers and

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cookies she has, eating all of them along with toast and peanut butter until she feels ill, and then forcing herself to vomit. She is sleepy after this and goes to bed. Diana’s dentist has warned her that her tooth enamel has sustained some damage from her vomiting, which she has done to varying degrees since age 14. Since Diana believes that, she “manages the amount,” she is unconcerned that it will be a danger to her health. Diana and her therapist, Ms. Lyons, worked in therapy to help Diana manage her emotional state after her breakup. When Diana was more stable, Ms. Lyons brought up the issue of Diana’s habits after Diana had a dental appointment. Ms. Lyons: So let me clarify this. You know that the binging and vomiting hurts your teeth, am I right? Would you say that the tooth enamel problem might be a reason you would consider reducing the amount of vomiting that you are doing? Diana: I guess. It never bothered me until he said I would need to have implants or my teeth capped. I never thought it was going to be so serious. Ms. Lyons: Well, if you are ready to think about stopping maybe we can talk about how your vomiting works for you. Diana: You mean about my weight? Ms. Lyons: Yes, I think that’s part of it, but there’s another part of the binging and vomiting that I think works for you, too. Like when you and Chris had those fights and you felt like you were at the end of your rope. Diana: I see what you mean. Like it’s a tranquilizer. Ms. Lyons: Exactly. So if we could work together on that part—so you could tolerate your feelings better—you might not need to binge, then. Diana: Okay. Ms. Lyons: And if you could work on the weight control function of the vomiting just a little, it might give us some breathing room until we help you enough with the feelings part. Diana: So how do you mean? Ms. Lyons: I think it might be pretty challenging to learn new ways to manage your feelings when you are upset, so it could take a little while. But one thing we could do for your teeth right now would be for you to try and vomit less often after regular meals. Like, for

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example, you could do things that keep you away from the bathroom right after you eat until the urge passes. And if you ate more consistently, so you would not feel so hungry and tempted to binge, it might decrease the number of times that happens. This way, we might reduce the harm to your teeth until we got the other reason for your binges better squared away. Ms. Lyons and Diana set a target goal for Diana to take a walk every night right after dinner to try and reduce her vomiting by two or three times per week. Co-morbidity associated with eating disorders can mean caring for patients with Axis II co-morbidity for whom dual responsibility treatment is more challenging (see Chapter 12). Collaboration and communication in dual responsibility treatment must be more frequent. This open communication can prevent inconsistent or incomplete instructions to the patient, who has complex eating and emotional dysregulation problems. A very helpful strategy is to have conjoint sessions (with all the treatment team in one room) at scheduled intervals. This maximizes the impact of care provided by a consistent group with a single message and allows for correction of miscommunications in “real time.” It also can facilitate the patient advocating for her needs with the treatment team. Physical illnesses can also be present in patients with eating disorders and complicate treatment. Type I diabetes mellitus patients who have eating disorders, for example, often discontinue or decrease insulin dosage to lose weight. Patients who do this are at high risk for poor metabolic control. In the short term, this can cause diabetic ketoacidosis, which can be fatal. In the longer term, this poor control can accelerate the long-term vascular consequences of insulin-dependent diabetes mellitus. Very close monitoring and frequent communication with medical providers must occur in this instance. Unambiguous communication to the patient and her family about the medical risks of this behavior must occur. When possible, it helps if psychotherapy and medical care can occur in the same physical location, so that laboratory values are immediately available to everyone treating the patient. If this is not the case, rapid electronic communication is a must. The medical care team must consult with the patient and the psychotherapy and/or pharmacotherapy care team to incorporate insulin and blood sugar management into the patient’s treatment plan. Adherence to diabetes care must be monitored as a part of therapy, along with eating habits and exercise.

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Finally, co-morbid substance dependence is a known factor that predicts poor outcomes in bulimia nervosa (Hay, Bacaltchuk, & Stefano, 2004). When this combination of disorders exists, it may be helpful to sequence treatment for these disorders or to consider brief intensive outpatient interventions to rapidly address both behaviors. The combination of substance abuse and eating disorders in the same patient can often be conceptualized as stemming from a general pattern of impulsivity, affect intolerance, and poor coping skills. Treating these patients is a challenge. It requires careful treatment planning and sequential goal setting. Good communication between care providers is vital to a positive result.

Relapse Prevention A final issue in working with patients who have eating problems is the need to clearly establish a plan to counter relapse. Patients must expect that being better may not mean being perfectly recovered. Each slip in the course of treatment should be used as an opportunity to learn more about the triggers for the patient’s behavior and about the patterns of thinking that foster relapse. The patterns of thinking that foster full-blown relapse after one or two occurrences of eating that does not go according to plan (e.g., “I’ve blown it now”, “I’ve ruined all my hard work”, “I need to make up for the cake I just ate”) are fairly wellknown. Patients must learn how to recognize and disengage from this type of thinking and return to the plans for food habit management that worked for them in treatment. Emily, a patient who has recovered from bulimia and who is receiving antidepressant medication, is a good example of how a brief intervention can help the patient get back on track. Emily is a 22-year-old woman who was hospitalized for anorexia at age 16. Although she sustained a good recovery with respect to weight restoration, she began to struggle with binging and purging during her senior year in high school, and eventually received treatment for it with psychotherapy and antidepressant medication. Emily saw two different providers in coordinated care for her treatment but has not seen her therapist for six months, following a several-month period of abstinence. Emily was evaluated by her psychiatrist, Dr. Frank, in a routine medication management visit. She told Dr. Frank that things had not been going well; she had had a two-week period of nearly daily binging and vomiting that started after she overate at a family party. Dr. Frank determined that Emily had been taking her antidepressants after vomiting (so she was certain that Emily at least had not been undertreated

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pharmacologically). She and Emily reviewed what Emily had learned in therapy about relapse and what the plan had been about how Emily was to manage slips. Emily talked about how she had the plan to eat regularly and to work to abstain from vomiting, but that she felt so disheartened by failing to remain abstinent that she had just “given up.” Dr. Frank reviewed with her how common slips can be and that Emily needed to take steps now to get back on track and avoid a full-blown relapse. Emily recommitted to her plan and was given an appointment to check back in a week. Treating patients with eating disorders is a good example of how collaborating closely with another provider can be beneficial. These are challenging conditions but clear communication may increase our effectiveness. Although psychopharmacological treatments are of limited use until weight restoration has occurred in anorexia, the patient’s primary care physician must be involved in treatment. Antidepressant medication has a role in weight-restored patients with anorexia and in conjunction with CBT in bulimia. Collaborative care in this circumstance may involve two or three providers with the common goal of restoring mental and physical health to the patient.

Combining CBT and Medication: An Evidence-Based Approach by Donna M. Sudak Copyright © 2011 John Wiley & Sons, Inc.

CHAPTER

9 Combined Treatment for Schizophrenia OVERVIEW Antipsychotic medications are the standard of care for both the acute and chronic symptoms of schizophrenia. Although these medications have made a revolutionary difference in the management of psychotic illness, their effectiveness is far from complete. Residual symptoms in schizophrenia are common. Large numbers of patients continue to experience positive symptoms even when fully treated with medication. Residual symptoms like delusions, hallucinations, and disturbances in thinking are debilitating and dangerous. In addition, negative symptoms of schizophrenia are far less amenable to medication treatment and are often associated with disability and poor outcome. The lack of a complete response to medication and the additional burden of interpersonal and cognitive problems in schizophrenia makes additional interventions that can improve desirable outcomes. CBT in combination with antipsychotic medications can help schizophrenic patients function better and reduce morbidity and mortality. An important note about combining CBT and medication in schizophrenia is that although many of these interventions may be useful for the patient who has psychotic symptoms that are a result of another disorder, there is presently limited or no data to be certain about such a recommendation. A significant problem with antipsychotic medication management in schizophrenia is medication nonadherence. The CATIE trial (Clinical Antipsychotic Trials of Intervention Effectiveness), a large, multicenter naturalistic trial comparing antipsychotic effectiveness, found that greater than 60% of patients 139

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were not adherent to treatment regardless of the type of medication prescribed (Lieberman et al., 2005). Nonadherence is a well-known factor in relapse and hospitalization in schizophrenic patients. CBT combined with medication clearly improves adherence, as a subsequent section of this chapter will describe. In addition, this chapter will summarize the evidence for combined treatment with medication and CBT in schizophrenia and provide particular examples of such treatment in action. Other forms of psychological treatments (family therapy, social skills training, and cognitive remediation) have also been shown to be helpful in schizophrenia (Patterson & Leeuwenkamp, 2008), and elements of these approaches can be used in conjunction with CBT and pharmacologic treatment for this disorder, as needed. Some data indicates that early, successful treatment for schizophrenia may potentially have long-term beneficial effects on outcome (Lieberman, 2000), so effective adjunctive treatment that augments the positive benefits of medication could prove even more valuable to patients with a new onset of the disorder. Medications and CBT could potentially act synergistically in schizophrenia. For example, effective pharmacotherapy may allow patients to concentrate better, to think more clearly, and to sleep better, and therefore better attend to the tasks of CBT treatment and self-care. The combination has the potential to be deleterious as well—patients in therapy who develop side effects to medication could interpret these side effects in a delusional manner and then mistrust further treatment efforts. For this reason, sensitive and careful communication with the patient and between providers in dual responsibility treatment can make a genuine difference in treatment acceptability. Patients with schizophrenia are at varying stages of readiness to understand the illness and to take the steps to manage it effectively—poor cognitive function, prior belief systems, denial, and the burden of psychotic symptoms slow the process. Family experiences and beliefs about medication and mental illness are also key variables that impact the outcome. Also, the patient’s readiness must be considered when planning the timing of interventions and the amount of information given to the patient at each therapeutic encounter. Patients must be able to understand what is presented—and cognitive deficits are common in schizophrenia. Repetition of small quantities of information and making certain the patient clearly understands the information are important strategies for providers to remember.

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EVIDENCE FOR COMBINING CBT WITH MEDICATION IN SCHIZOPHRENIA Evidence That CBT Combined With Medication Improves Adherence Several early randomized controlled trials with very small numbers of patients (Kemp, Hayward, Applewhaite, Everitt, & David, 1996; Lecompte, 1995; Perris & Skagerlind, 1994) demonstrated that CBT sessions facilitated adherence to medication in psychotic patients. One study (O’Donnell et al., 2003) that did not find a major advantage in adding CBT to medication in schizophrenic patients was in patients who had an unusually high noncompliance rate (72%). These patients were provided a five-session intervention that was thirty to sixty minutes in length. One year after this intervention, no change in adherence was observed in the CBT-treated group. Patients who are very nonadherent may need more CBT treatment or a longer period of continuing booster sessions. Studies of patients with schizophrenia combining CBT with medication for adherence identify treatment targets as identifying and changing attitudes about treatment that predict medication lapses and increasing the patient’s insight about the illness. The difficulty with cognitive processes (memory, executive function) that occurs in schizophrenia (Ascher-Svanum, Zhu, Faries, Lacro, & Dolder, 2006) can be a significant problem with respect to taking medication as directed. Astute providers will use behavioral treatment to diminish these difficulties in combined treatment with medication and CBT.

Evidence That CBT Combined With Medication Improves Positive and Negative Symptoms of Schizophrenia In addition to facilitating adherence, there is evidence that supports the efficacy of CBT approaches to other manifestations of schizophrenia that are not treated or incompletely treated by medication. More research must be done to ascertain which schizophrenic patients will benefit from combining CBT with medication, and to determine whether the timing of such interventions improves outcomes. There have been a limited number of randomized controlled trials with CBT in schizophrenia. CBT interventions have been tested both in groups (Drury, Birchwood, Cochrane, & Macmillan, 1996) and in individuals (Tarrier et al., 1998; Sensky et al., 2000). Several small, randomized controlled trials of CBT for schizophrenia indicate that CBT

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approaches are effective for positive symptoms when combined with medication. Tarrier and colleagues (1998) showed that CBT had a greater effect on positive symptoms than adding either supportive treatment or no treatment to medication. Both the supportive and cognitive behavioral therapy groups had an equal advantage over no therapy in long-term follow up, however (Tarrier et al., 2000). Sensky and colleagues (2000) found that the positive effects of CBT compared to a supportive therapy (called “befriending”) were far-reaching and continued to accrue nine months after therapy was over. This benefit occurred in patients who had persistent symptoms on adequate pharmacotherapy. Unfortunately, the numbers of patients are too small to make firm recommendations about when to employ CBT. The National Health Service in Britain currently mandates an initial course of CBT along with medication in the first episode of schizophrenia. Data from this experience will be extraordinarily helpful to us about the effectiveness of adding CBT to medication in clinical practice. Wykes and colleagues (Wykes, Steel, Everitt, & Tarrier, 2008) recently performed a meta-analysis of 34 studies of CBT for schizophrenia. Targeted symptoms responded to treatment in all the studies reviewed, but those studies without blind raters had inflated effect sizes. This review and meta-analysis included both group and individual treatment and measured therapeutic effects other than adherence, including positive and negative symptoms, functioning, mood, hopelessness, and social anxiety. Positive symptoms were evaluated as the main outcome variable, but CBT had a significant positive effect on all the other outcomes, except for hopelessness. The ratings of hopelessness notably increased in three of the four studies measured in this meta-analysis. Clinical caution is warranted and until further data about this finding is obtained; it is advisable to maintain heightened sensitivity about hopeless ideation in patients in CBT. Other recent studies indicate that CBT has a significant impact or decreasing hopelessness (see below). Durability of treatment effects was not evaluated by the Wykes meta-analysis. More data from randomized controlled trials are needed to make a definitive statement about the evidence for CBT as a brief treatment for positive symptoms independent of medication. However, because residual positive symptoms are common in patients receiving medication, and increasing a patient’s functional capacity would be quite helpful, CBT could be employed in briefer ongoing medication management sessions with chronic patients. Research should be conducted to evaluate the effectiveness of combining

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ongoing maintenance CBT with medication treatment for residual symptoms of schizophrenia.

FUNDAMENTALS OF THE CBT APPROACH TO THE PATIENT WITH SCHIZOPHRENIA The CBT approach to schizophrenic patients has been well described in several treatment manuals (i.e., Kingdon & Turkington, 2005). Several important features of the approach with particular relevance for combined treatment are detailed here. The goals of treatment in CBT for psychosis are to enhance adherence to treatment, decrease symptoms, and increase the patient’s day-to-day function. These goals are accomplished in the context of an empathic and active therapeutic alliance.

The Therapeutic Relationship One key aspect of the CBT approach to the patient with psychosis that could benefit all patients irrespective of their diagnosis is the implementation of a therapeutic relationship that “meets the patient where he is” and seeks to understand the patient’s beliefs about the origin and meaning of his illness’ symptoms. The therapist makes a genuine effort to understand the patient’s perspective regarding the origin and phenomenology of his or her particular experience of psychosis. Next, the therapist and patient work together to create an adaptive framework to understand and more effectively respond to the illness and to reduce any ideas the patient has about the illness being his fault. Collaboration with the schizophrenic patient must include a respectful discussion of the patient’s experience and beliefs—even when those beliefs are not shared by the therapist. The therapist becomes an “expert” about the psychotic experience of the patient and the patient’s subsequent explanations for how his symptoms are produced. An important aspect of forming the therapeutic relationship is to normalize the patient’s experience of psychosis based on a stress-vulnerability model. Great care is taken to reduce the stigma associated with the illness. This increases hope and motivation. A recent study found that a CBT-based intervention in schizophrenia had a significant effect in reducing hopelessness, which mediated an increase in patient activity (Hodgekins & Fowler, 2010). Because the data about hopelessness are somewhat contradictory, as described earlier in this chapter, clinicians

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must be careful to monitor hopeless thinking in the schizophrenic patients they treat.

Enhancing Adherence to Pharmacotherapy One function of the sensitive and respectful collaboration with the patient that characterizes CBT is to make it easier for the patient to accept the need for pharmacotherapy. If therapy normalizes the patient’s symptoms, certain functions of pharmacotherapy will seem more logical to the patient and increase the likelihood of adherence. Sleep disturbances, for example, can be a stressor that provokes hallucinations. This phenomenon can be explained by the fact that sleep deprivation in humans produces hallucinations. The patient can also observe the relationship between sleep problems and any increase in hallucinations with a sleep diary. If the prescriber explains that medication will help the patient to sleep, then patients are more likely to take medication regularly. Such a collaborative conceptualization does not require that the patient accept a diagnosis of schizophrenia, only that the patient focus attention on his symptoms and develop an explanation for these that is acceptable and adaptive. Specific medication effects that benefit the patient’s painful symptoms should be highlighted by every care provider. Medication effects that are helpful that are not recognized by the patient should be directly discussed at every therapeutic encounter. These benefits might, for example, include positive effects on concentration and attention. The goal is a decrease in symptom severity and an increase in patient’s function. In combined treatment for schizophrenic patients, adherence work must include the acknowledgment of the difficulty of coping with a chronic illness. The experience of having an illness and taking medication is almost an inescapable part of life. Patients who believe this undeniably benefit with respect to their self-regard. In addition to reminding patients of the positive benefits of medication, any unusual thoughts or delusions about medication (such as misinterpretation of side effects as due to the devil, for example) must be carefully elicited in treatment and be discussed by all providers. Many patients with schizophrenia have an incomplete picture about what causes their problems, which can lead to the development of delusional explanations for the symptoms they have. Learning about the illness can increase adherence and decrease delusions. Encouraging the patient to try controlled behavioral experiments with medication and draw conclusions from the data can be another important strategy in treatment.

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A joint solution-focused approach to any side effects of medication is critically important. Everyone involved with the patient must work to find remedies for unwanted medication effects. Patients will be far more tolerant of these often troublesome physical effects of medication if they believe there is an active effort to find solutions. Practical problems can also be significant barriers to psychotropic use. Care providers must engage in active, creative problem-solving in this instance. This is a time when one must remember the patient’s life circumstances and the formidable obstacles that may exist because of the illness or the psychosocial barriers it creates. For example, patients who are homeless or who do not have stable housing are less capable of sustaining a daily routine that they can associate with taking medications.

Varying the Structure of CBT Sessions and Providing Psychoeducation An important difference in CBT with schizophrenic patients is specifically modifying the structure of sessions to match the patient’s needs. The length of sessions may be briefer and the agenda more fluid and less goal-focused as the patient’s symptoms require. Careful observation of the patient’s anxiety level guides these adjustments to the session structure. Shifting to more casual topics of conversation can help reduce anxiety and keep the interchange going. Therapists must be careful to support and reinforce patients to make better choices and skillfully cope with the illness. Psychoeducation is a key component in CBT for schizophrenia. In dual or single responsibility treatment, the therapist and pharmacotherapist must remember that there are significant cognitive deficits produced by the disorder. This means that educational materials must be provided repeatedly, both in oral and written form, and in brief, easy-to-remember formats. Cognitive deficits in schizophrenia are not improved by medications except with respect to removing the distraction of positive symptoms and decreasing anxiety. Because learning and memory are key requirements of successful psychotherapy, care providers must attend to the significant problems of poor attention and memory that exist in schizophrenic patients. Psychoeducation in patients with schizophrenia focuses on the patient’s developing an understanding of the illness, generally from a stress-diatheses model, and of the very important role of medication in maintaining health and well-being. Patients are taught self-monitoring to recognize symptoms and

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symptom triggers. Skills training can increase the patient’s ability to deal with symptoms in a more adaptive way. The following case example illustrates the benefits of CBT in schizophrenic patients. Gary is a 49-year-old man with a 30-year history of psychiatric difficulties. He initially presented for treatment at age 19 after the death of his elder brother from cancer. At that time, he was a student at a local junior college. Gary had an extensive history of childhood health problems, including multiple allergies, asthma, and respiratory infections. These health concerns hampered his social development. He was frequently kept home from school, and he was never permitted to do many of the social activities his brother did. For example, he did not go to summer camp and was unable to join the Boy Scouts. Gary struggled in school. He always believed he was “slower and stupider” than other kids. When Gary started high school, his brother was diagnosed with stage three Hodgkin’s lymphoma. Naturally, his family’s attention became entirely focused on managing his brother’s illness. Gary withdrew from most activities and smoked marijuana for much of the day. He was able to graduate from high school, but his grades were so poor that his school counselor suggested he attend a junior college before applying to college elsewhere. At the end of Gary’s first year of junior college, his brother suddenly deteriorated and died of pneumonia. Gary began to stay in bed for increasing periods of time after his brother’s death. He barely appeared for meals and often ate at night after his parents had gone to bed. His parents initially attributed this to a grief reaction. They were so stricken by their own grief that they paid even less attention than usual to Gary. As his sophomore year progressed, Gary became increasingly preoccupied with bizarre physical complaints. He said he felt like there were “electrical currents” in his legs and arms, and he had a “constant buzzing” in his head. Eventually he developed a belief that newscasters on television were speaking about him and influencing his day-to-day activities. He was committed to a hospital after he threw all the family’s television sets onto the front lawn because he was so frightened of being controlled by them. Gary’s course of treatment over the past 30 years has been complicated by his difficulty taking medication regularly. He does not believe he has schizophrenia. He believes his symptoms represent evidence that his brain has been permanently damaged by his marijuana use and that psychotropic medication will not help this problem. Gary was hospitalized three weeks ago and discharged to after-care with a psychiatrist, Dr. Clark, and a psychologist, Dr. Baxter, who work in the same

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practice group. They met jointly with Gary and his parents, with whom he still lives. Dr. Clark explained to Gary that he agreed with him that medication might not help the brain damage that Gary was concerned about, but that medication could possibly help his sleep problems, which were severe. He encouraged Gary and his parents to describe what they saw as helpful effects of the medication. After doing so, Gary agreed to take his medication and took a written list of reasons to do so to remind him of his resolve to take it every day. Dr. Baxter, who was to be Gary’s therapist, agreed to focus on the physical symptoms Gary experienced to help him to cope better with them. Finally, Gary’s parents agreed to not “debate” with him about whether his physical symptoms were “real” and to stop nagging him about medication, since that increased Gary’s distress and anger.

SPECIAL PROBLEMS IN TREATING THE PATIENT WITH SCHIZOPHRENIA Managing Delusions and Hallucinations CBT, as adapted for psychotic symptoms, has a specific method to help patients counter these frightening and debilitating phenomena. A detailed explanation of how to accomplish this is available in several recently published treatment manuals (Wright, Turkington, Kingdon, & Basco, 2009; Kingdon & Turkington, 2005). Delusions and hallucinations are frequently only partially responsive to medication, so tools to help patients actively cope with them can reduce distress and increase function. The therapeutic process with delusions and hallucinations begins with gentle curiosity and encouragement to the patient to discuss them in session. The therapist’s curiosity can teach patients to observe delusions and hallucinations more objectively. Such observations can lead to an awareness of the triggers that increase them. The therapist helps the patient to learn to experience hallucinations without the need to act on them in any way and to use coping strategies to minimize distress when they occur. Finally, the patient is encouraged to gradually test and reconsider illogical beliefs and more logically respond to hallucinations. When patients have delusional beliefs, it helps them to consider the possibility that these beliefs are ideas in their mind with which they can learn to cope. Delusional beliefs, just like other automatic thoughts, are not all held equally strongly. These ideas vary in the degree to which the patient sees them

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as true. Linking events with delusional ideas and the resulting behaviors and emotional states can help the patient to develop more effective coping strategies in schizophrenia just as usefully as in depression. Simpler thought records that include a situation, the automatic belief, and the consequence can be quite helpful. Patients can use the basic cognitive model to help reduce triggers for hallucinations and delusions and to evaluate and change subsequent behaviors. An example of evidence gathering in a patient with schizophrenia is Bonnie, a patient in the hospital with a long history of troublesome delusions. Bonnie is a 42-year-old woman with a long history of schizophrenia and delusional beliefs; she has a belief that other people know what she is thinking and know that she has a mental illness. Bonnie hears voices tell her that she will be “experimented upon” by doctors and psychiatrists. She has refused medication treatment because she has an idea that it will “just make her brain worse.” Bonnie has had multiple hospitalizations for poor self-care. Fortunately, she has retained her ties to her sister, who checks in on her and calls a mobile team when Bonnie is extremely disorganized. Bonnie generally responds well to medications in the hospital, which she agrees to take when she is there to “get away from the doctors” more quickly. She was hospitalized three days ago. On this particular hospitalization, Dr. Smith, the psychologist on the unit, and Dr. Jonas, the attending psychiatrist, met with her to discuss her difficulties taking regular medication. They helped Bonnie to generate a table (Table 9.1) about the ideas she had about medication, including the evidence for and evidence against medication “making her brain worse.” Table 9.1 Bonnie’s Evidence Table Idea: Medicine Makes My Brain Worse Evidence For

Evidence Against

I hear voices telling me that I am experimented upon by Dr. Jonas.

Voices are a symptom of my schizophrenia.

There are articles about experimental treatments that hurt people in the newspaper.

Those articles were about cancer patients. They don’t apply to me.

Medicines can harm you and have side effects.

The PDR had all the side effects in it. They weren’t so scary. I’ve taken the pills here in the hospital and felt fine.

I know about Tuskegee and they experimented on people there.

That was a terrible event, but I have no proof it is happening to me now.

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This evidence about medication treatment persuaded her to try to take antipsychotic medications after discharge. In dual responsibility treatment, it is very important that both providers understand and agree that these techniques to combat psychotic symptoms are useful. Otherwise, mixed communication to the patient can occur and derail treatment. For example, prescribers who believe a purely biomedical conceptualization of schizophrenia may disparage patient efforts to normalize and cope with hallucinations and instead respond to the occurrence of these symptoms as an indication to increase or change medication. On the other hand, a careful and thoughtful review of pharmacotherapy options is indicated when patients are struggling to cope with psychotic symptoms with less success. Patients would be confused if one provider is indicating that delusions or hallucinations are evidence of a chemical imbalance while the other provider has a purely Socratic approach to them. Both providers must carefully assess treatment outcomes and work toward the best possible functional outcome for the patient. Patients should be a part of the team, and taught to actively self-monitor for stressors and symptoms.

Managing Negative Symptoms The CBT conceptualization of schizophrenic patients is that many behaviors that the patient have are efforts to cope with psychotic symptoms. For example, many patients with schizophrenia avoid activities and interpersonal relationships in order to decrease stimulation and anxiety, which cause the subsequent appearance of positive symptoms. Patients can appear to have negative symptoms when these coping mechanisms are overused. Helping patients with negative symptoms involves creatively using standard methods of behavioral activation tailored to the capacity of the patient. Patients must be given the opportunity to “opt out” of out-of-session practice if it becomes too stressful and subsequently build in smaller steps to increase activity (i.e., taking a walk in the mall in the early morning, when it is less crowded, without speaking to anyone). The goal is to set very short-term (daily or weekly) goals that are sufficiently manageable to increase the patient’s motivation without overwhelming her.

Assessing for Suicide Risk Schizophrenic patients are particularly vulnerable to the development of suicidal thinking and to suicide completion. The treatment team must be highly

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active in assessing suicidal thinking in patients with schizophrenia, and help them develop alternative perspectives and positive coping. The risk of completed suicide in schizophrenia is greatest in young male patients who have been recently diagnosed and who are of high intelligence. Patients are also more vulnerable if they have families who have high expectations of them. Many young people newly diagnosed with schizophrenia anticipated a far different future and are shattered by the meaning the diagnosis has to them. Combined treatment with medication and CBT may have particular benefits soon after diagnosis, because CBT takes an active problem-solving approach to symptoms and works to combat stigma by normalizing symptom development. A purely psychoeducational approach in some patients can mean accepting what they see as a stigmatizing diagnosis with no hope for a happy life in the future. This can increase suicidal thinking. In addition to risk management regarding suicide at the time of initial diagnosis, close monitoring and unambiguous questions about suicidal thoughts and plans need to be part of the ongoing management of schizophrenic patients. These individuals have a chronic increased risk for suicide. Suicidal thoughts can be assessed, similar to their assessment in depression (see Chapter 5). If patients develop delusions or hallucinations with suicidal content, urgent consultation between providers must occur and hospitalization must be considered. Any plans or behavioral rehearsal of suicide plans further increase risk, just as in depression, and must be managed accordingly. A particular advantage of medication use in suicidal patients is to use clozapine as the primary treatment for psychotic symptoms. Although clozapine has some significant risks (in particular, the risk of agranulocytosis) and the need for diligent, frequent blood counts, it has an evidence-based advantage of resulting in a clear decrease in suicide rates.

Preventing and Managing Hospitalization Every patient with schizophrenia has the potential to be hospitalized at some point in the illness. Hospitalization is expensive and demoralizes the patient. Hospitalization often incurs the loss of housing and employment in a patient who has tenuous social supports. Patients who are hospitalized for long periods often lose contact with the limited social network they have. This makes prevention of hospitalization an important goal. One way to accomplish this is to carefully identify early signs of relapse as a part of each treatment contact. A team of providers can be an advantage to the patient, because two

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observers work with the patient to identify prodromal signs and symptoms and to formulate strategies to prevent further decompensation. Prompt communication can mean that the patient can avoid inpatient care, as the example of Gary illustrates. Gary was seen in his bimonthly medication management session. His psychiatrist, Dr. Clark, noticed that he was more poorly groomed, and he had missed his last two outpatient therapy visits. Gary said he was taking his medication as regularly as he could, but he often fell asleep in front of the television before he took his bedtime dose. Dr. Clark reviewed Gary’s symptoms with him—he had been spending more time in bed because he felt the buzzing in his head was worse. He called Dr. Baxter, Gary’s therapist, while Gary was in his medication management session, and determined that Gary could see her for a session that afternoon. Gary agreed to take his evening medication when he sat down to watch television to see if that helped him to remember it better. During his appointment with Dr. Baxter later that afternoon, Gary revealed that his mother had just been diagnosed with cancer. He was very upset about this, and began to talk about how he had not ever thought about what he would do when his parents died. Dr. Baxter gently added that the diagnosis of cancer would be especially upsetting to Gary because of the death of his brother, but that his mother might have a different course of the illness. Nevertheless, Dr. Baxter agreed that it was good, although difficult, to begin to think together about what Gary will do in the future, because his parents are aging and he will need a plan. They agreed to work on this problem together for several sessions once Gary began to feel better, and to have a family meeting about it. Dr. Baxter also discussed with Gary the fact that he hated to take his medication at night because it made him drowsy and interfered with his watching baseball on television, which was one of his few pleasures. Dr. Baxter: Well, it makes sense to me that taking your pills would be difficult, because I know how much baseball means to you. Can we spend a few minutes talking about some possible solutions to this problem? Because I am afraid if you keep missing doses you will eventually feel worse and need to go back to the hospital. Gary: I just don’t see any way around it. The games can last a long time, and I fall asleep in the chair. If I take the pills, I fall asleep for sure and I miss the game. So I feel like I am just stuck.

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Dr. Baxter: I have a few ideas. First, we could talk to Dr. Clark and see if there is any way to prescribe something less sedating. But that will take time. So we need a solution for now that will let you take medicine and watch baseball. Do you have DVR or a VCR? Gary: We have a VCR. Dr. Baxter: Would you be willing to try recording the game and watch it the next day? This way you could see the game for sure and you could take your pills. Gary agrees. Dr. Baxter and Gary make a plan for him to stop at the drugstore on the way home to buy some videotapes. Poor adherence to medication is often a reason for relapse and rehospitalization. We have evidence that adherence may be helped by the addition of CBT to patient management. Other precipitants for hospitalization may include psychosocial problems—including financial trouble, lack of safe housing, and lack of proper nourishment. Both providers in dual responsibility treatment can work to familiarize themselves with what social services are available, and help the patient access them. Having two sources of information to help with psychosocial problems is an advantage because of how daunting the task of obtaining help can be. Aggressively managing substance use is also of paramount importance. Often it is easy to dismiss this as impossible, or to see the drug and alcohol use as an understandable response to the psychotic illness. Don’t give up. Accept successive approximations of sobriety and maintain a hope that change is possible. Therapy must help the patient prioritize and solve the problems that led to substance misuse. An integrated team of providers can reinforce the patient’s morale and her resolve to keep trying. If the patient is hospitalized, the outpatient team should remain involved with the patient so that continuity of care is maintained and should provide the patient with a clear plan for discharge. Hospitalization, just like any relapse, should be viewed as a good time to get more information about the problem. It is an opportunity for the patient to learn better ways to manage stress, identify and troubleshoot risk factors and triggers for decompensation, and then make a better plan with the team for the future.

Managing High-Risk Behaviors and Trauma Schizophrenic patients are uniquely vulnerable to traumatic events. Patients with schizophrenia are at risk for trauma because they may have poor judgment

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and poor recognition of dangerous situations. Patients with schizophrenia are frequently cognitively disorganized. This increases their vulnerability to physical and sexual trauma. Psychotic symptoms themselves can traumatize patients. Imagine what it is like to be constantly assailed with persecutory hallucinations that ceaselessly torment you, rob you of sleep, and prevent functional behavior. Delusional beliefs are a significant source of pain and suffering for patients. Care providers need to help patients contend with trauma from within and without. Patients with schizophrenia also often live in circumstances that make them more vulnerable to traumatic events; they are economically disadvantaged and frequently reside in neighborhoods with high crime rates. A disproportionate number of schizophrenic patients are homeless and alone. Disorganized thinking increases a patient’s vulnerability to financial exploitation, physical and sexual trauma, and sexual exploitation. The most vulnerable schizophrenic patients are patients who have co-morbid substance use disorders because of the increased impairment of judgment and impulsivity that occurs when the patient is intoxicated. A particularly vicious circle occurs when traumatized patients develop more paranoia and exacerbation of symptoms or become more prone to social isolation. Providing patient care to vulnerable patients involves advocacy, specific knowledge of the social services available to the patient, and patience. Dual responsibility treatment can be an asset here—a team can be more vigilant advocates for the patient and increase the frequency of monitoring and support. Patients with schizophrenia are also prone to high-risk health behaviors throughout their illness. In addition to higher rates of drug and alcohol abuse (Goldman, 1999); they have a much higher prevalence of cigarette smoking (Bobes, Arango, Garcia-Garcia, & Rejas, 2010). Smoking-related deaths are much increased in patients with schizophrenia relative to the general population (Brown, Inskip, & Barraclough, 2000). Schizophrenic patients frequently have poor nutrition and limited access to health care. The patient’s disorganization and difficulty with executive function can result in poor planning about health-related matters. High-risk sexual behavior is another ongoing concern. Targeted interventions that decrease high-risk behaviors as much as possible are important elements of treatment. For example, the team can inquire about meal planning, access to grocery stores, and scheduled time to cook, and then plan strategies to improve nutrition. Consistent reminders about condom use can increase the likelihood of protection during sexual encounters. Providers

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need to routinely inquire about high-risk behaviors and trauma, work to help the patient employ skills to cope, and communicate with each other on the patient’s behalf. For example, if a primary care provider notes evidence of physical trauma and informs the mental health team, the patient can work in therapy to develop safety plans and decrease the risk of future harm. The case of Betty, a woman in treatment in a community mental health center, demonstrates how a team approach can benefit vulnerable patients with schizophrenia. Betty is a 35-year-old woman with a 16-year history of schizophrenia. She has not had a permanent residence for ten years. Each time she begins to be more stable in transitional housing, she reinstates contact with Jack, her former boyfriend. Jack is an active crack cocaine user who has exploited Betty in the past by taking her Social Security check, sexually exploiting her (including sexually selling her to his friends), and providing her with crack cocaine. Betty has had many “false starts” in attempting to leave her relationship with Jack, with limited success. Betty has just been released from her 25th hospital stay and has been placed in a transitional residence with six other women and onsite supervision. The psychiatrist at the mental health center where Betty receives her outpatient care got Betty’s permission to contact the treatment team at the new transitional residence during her first outpatient visit after discharge. She informed them about Betty’s past history of relapses. They set up a meeting with Betty and the entire treatment team to discuss the goal of keeping Jack out of her life. Betty agreed at this meeting that staying away from Jack was a good idea. However, Betty had very limited ideas and insight about why she continually relapsed and reconnected with him. In the meeting, Betty’s therapist did a careful behavioral analysis of how the problem generally began. They discovered Betty had the most trouble when Jack would contact her on weekends, when she had very little to do, and particularly on those weekends when Betty received her Social Security check. Solutions to this problem were jointly considered by Betty and the team. Betty agreed to have her checks paid to a guardian until she was more stable. She was initially reluctant to do this, but when her therapist pointed out that she never saw her money much of the time because she gave it to Jack, it made sense to Betty. The team made a commitment to help Betty actively plan her weekends, and the staff at her housing agreed to make extra efforts to seek her out at those times. In the weeks following the team meeting, Betty used activity schedules in her one-to-one therapy sessions to plan positive activities. She agreed to attend a Narcotics Anonymous meeting at her transitional housing and to contact an

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abused women’s group. Betty still hears from Jack, but her contact with him is more limited and she is more stable. Another high-risk behavior for schizophrenia patients is substance misuse. We know patients with schizophrenia have a high risk of co-morbid substance abuse or dependence (Regier et al., 1990). Care providers must work with schizophrenic patients to help them curtail or stop using substances because they increase the risk of other high-risk behaviors and make the illness worse. Substances contribute to disorganization and nonadherence. Patients with both substance abuse and schizophrenia have a higher risk for homelessness (Smith & Hucker, 1994) and more problems with psychosocial function. A recent study of a treatment that integrated motivational interviewing, CBT, and family therapy interventions showed a greater improvement in function and increased abstinence in patients with co-morbid schizophrenia and substance abuse or dependence. This improvement was sustained for 12 months after the end of treatment (Barrowclough et al., 2001). It helps patients when clinicians are nonjudgmental when discussing substance use; greater openness about the pattern of misuse will follow. A careful behavioral analysis can be an invaluable tool to plan for interventions to decrease use. Care providers must aggressively pursue harm-reduction and abstinence strategies whenever possible. It is important to be patient and accept successive approximations toward decreased use. One reason patients may use drugs and alcohol is to cope with residual symptoms. If this is what precipitates use, careful inquiry and consultation with the medication provider are indicated if the patient is in collaborative care. Patients may use substances to combat boredom or negative symptoms. Activity scheduling and problem solving, both in therapy and in medication management sessions, can help the patient to plan leisure time. Education, motivational interviewing, and cognitive and behavioral strategies may also be employed to help the patient reduce the use of drugs and alcohol. Patients can be unaware of the effects of the substances on their primary psychiatric illness and need persistent reminders of the negative outcomes related to their use. Consistent reinforcement and education from the psychiatrist, primary care physician, or therapists involved with the patient can help the patient stay on track and improve prognosis.

Managing Co-Morbid Medical Illnesses A critical component of caring for schizophrenic patients is helping them to obtain and adhere to medical care. Schizophrenic patients have an increased

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rate of significant medical illness and premature death (Brown et al., 2000). They have a substantially greater mortality from heart disease, stroke, and diabetes than nonschizophrenic patients (von Hausswolff-Juhlin, Bjartveit, Lindstrom, & Jones, 2009). There are multiple reasons for this phenomenon. First, patients with schizophrenia frequently lack access to good medical care. They can have psychotic beliefs about doctors or delusions about the physical symptoms they have. These ideas can prevent them from seeking medical care. Patients with schizophrenia are frequently unable to describe physical sensations in a clear and understandable way. Because of these problems, when patients with schizophrenia do seek medical care, many of their underlying physical problems are not properly diagnosed by the physician they see (Goldman, 1999). Other barriers to medical care include financial limitations and transportation problems that can make obtaining and keeping appointments a challenge. Cognitive disorganization may interfere with the patient making and keeping appointments as well. Think of the last time that you tried to make an appointment with your primary care physician. Was it easy to do? Did it require a fair bit of planning? What about a requirement for the capacity to tolerate frustration? And likely, you have health insurance, money, and transportation to your physician’s office. Now imagine your schizophrenic patient’s dilemma when seeking medical care. Patients with schizophrenia often also lack the cognitive skills to anticipate future problems and remember what physicians communicate to them. Another important problem is that physicians have significant biases about the care of mentally ill patients. First, physicians are not immune to the cultural biases that exist regarding psychiatric illness. Second, caring for schizophrenic patients is complicated and time-consuming. Primary care practice as it currently exists is ill-suited to this type of patient. Many primary care physicians are also not skilled at communicating with psychotic patients. Schizophrenic patients need coaching and practice to describe their problems and discuss their needs. This can be a tremendous benefit of therapy. Partnering with primary care physicians is another form of dual responsibility treatment that improves outcomes, including improving the rate of diagnosis of co-morbid medical conditions in such patients. The medical risk of second-generation antipsychotic medications compounds the psychosocial barriers to medical care. A majority of patients receive second-generation antipsychotic medications because they are easier to administer and have less severe immediate side effects. These medications also have

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a decreased risk of the development of tardive dyskinesias. However, as with most medications, there is no free lunch. Second-generation antipsychotic medications are significantly associated with the development of weight gain, diabetes, and hyperlipidemia (also known as the metabolic syndrome). This contributes to the increased mortality in schizophrenia (Newcomer, 2007). Coupled with this, schizophrenic patients are also more likely to smoke cigarettes, because the nicotine acts as a stimulant and combats negative symptoms and cognitive slowing. The combination of cigarette smoking and metabolic syndrome is lethal. Any efforts to help the patient curtail smoking will be of benefit. Too often, providers have the idea that nicotine addiction is a less significant problem compared to all of the other problems in schizophrenia, so they do not even attempt to address decreasing nicotine use. This is a costly disservice to the patient. When we undertake care for schizophrenic patients, we must commit ourselves and our time to helping them receive adequate medical care. This commitment requires us to allocate sufficient time to communicate with the patient’s medical care providers. The patient’s adherence to diet, exercise, and medication should be a part of the agenda in therapy. Often, the therapist and/or psychiatrist are the only people with an eye on the “big picture.” Armed with the tools of CBT, therapists and therapist prescribers can help patients communicate better with their physicians, adhere more substantially to medication regimes, and initiate and maintain new behaviors that promote wellness.

Combining CBT and Medication: An Evidence-Based Approach by Donna M. Sudak Copyright © 2011 John Wiley & Sons, Inc.

CHAPTER

10 Combined Treatment for Borderline Personality Disorder

T

he challenges inherent in prescribing for patients with borderline personality disorder and in maintaining good communication when multiple providers are responsible for treatment are well-known. Indeed, any patient with a personality disorder presents an increased level of complexity in clinical practice—patients with Axis II psychopathology have a higher risk for Axis I disorders that are more chronic and severe and for behavioral disturbances that complicate treatment. In addition, the defining characteristics of Axis II disorders mean that interpersonal problems will likely exist, and these can pose substantial difficulties in the therapeutic relationship. Multiply this by two providers and the problems can be exponential, even in the absence of unambiguous communication. This chapter will focus on working with patients with borderline personality disorder who require medication management. It may be possible to generalize the key principles in the chapter to patients with other personality problems, but the data about the efficacy of CBT for such patients is not available; sufficient research has yet to be conducted with specific populations of patients with other Axis II problems. One exception is that we do know, as previously reviewed, that patients with Axis II disorders in treatment for co-morbid major depression fare better in pharmacological treatment compared to briefer treatment with CBT alone (Fournier, DeRubeis, Shelton, Amsterdam, & Hollon, 2008). When brief therapy is the only alternative (for example, because of insurance issues), this information should inform treatment recommendations we make to patients who seek help for major depression and who have Axis II psychopathology. 159

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There is evidence that several forms of psychotherapy are effective treatments for borderline personality disorder, and psychotherapy is recognized as the most effective form of treatment for this disorder. Dialectical behavior therapy (DBT) was designed as a treatment that recognized the substantial prevalence of co-morbid conditions in these patients. DBT tailors the structure of treatment to facilitate working with patients who have both Axis I and severe Axis II psychopathology. Other models of psychotherapy have been tested for borderline personality disorder and have evidence of efficacy. These include two forms of therapy with a theoretical basis in psychodynamic psychotherapy: transference-focused therapy and mentalization therapy. Schema-focused therapy, a form of CBT, and IPT have also been tested and found to be helpful in smaller trials. Data regarding the combination of these treatments with medication or comparing medication and psychotherapy is limited, as are studies of patients with or without co-morbid Axis I disorders. This limits our ability to recommend best practices in combining treatments for borderline personality disorder. One study in patients without Axis I disorders indicated that combined treatment with fluoxetine and IPT was superior for patient symptoms to either treatment alone (Bellino, Rinaldi, & Bogetto, 2010). Clearly more work is needed to help us make better-informed treatment decisions in these complicated patients. A convention used in this chapter is to refer to the patient as female. This decision stems from my clinical experience with patients with borderline personality disorder and the greater prevalence of this diagnosis in women. Additionally, the chapter refers to psychotherapy with DBT combined with medication, but not to the other forms of psychotherapy that have been effective in clinical trials. This decision was derived from the emphasis of the text on combining treatment with CBT-based therapy and medication, and the fact that the largest body of evidence regarding CBT for borderline personality disorders has been with DBT.

TO MEDICATE OR NOT TO MEDICATE: THAT IS THE QUESTION Borderline personality disorder is, by definition, a problem that presents with a myriad of psychiatric symptoms. These can include manifestations of affective and cognitive dysregulation. Additionally, patients with borderline personality are frequently diagnosed with other Axis I disorders, including

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major depression, bipolar disorder, and psychosis. Substance abuse is a frequent co-occurring problem. Given this complexity, it can be tempting to treat every symptom with medication, resulting in the provision of numerous types and classes of medication to a very unstable patient. Conversely, the presence of an Axis I disorder can make therapy much less effective if it remains untreated. The overarching questions to consider regarding psychotropic medication use in these patients are: 1. Are any medications useful for the personality disorder itself? 2. Do co-morbid symptoms represent an actual Axis I disorder, or are they a manifestation of borderline personality disorder?

Evidence for Using Medication for Borderline Personality Disorder Evidence for the use of medication for borderline personality disorder is generally based on studies of small numbers of patients that target varying symptoms. For example, some studies are designed to evaluate the efficacy of medication for particular symptoms (i.e., low mood or impulsivity) and some are designed to evaluate overall disorder severity. A recent systematic review of existing evidence for pharmacotherapy in borderline personality found 27 trials that were randomized and controlled (Lieb, Vollm, Rucker, Timmer, & Stoffers, 2010). This well-designed review indicated that there were beneficial effects on specific affective symptoms using mood stabilizers, including topiramate, lamotrigine, and valproic acid, and for the antipsychotic medications aripiprazole and olanzapine when the patient has cognitive-perceptual symptoms. SSRI antidepressants did not appear to be effective mood regulators in this review. The authors caution that the evidence does not support effectiveness for any medication to decrease the overall severity of the disorder, advocate use only for specific symptoms, and state that the “robustness of findings is low.” Another meta-analysis exists that strongly advocates for the use of mood stabilizers and not SSRI antidepressant medication in patients with no Axis I mood disorders when attempting to treat depressed mood, impulsivity, anxiety, anger, and global functioning (Ingenhoven, Lafay, Rinne, Passchier, & Duivenvoorden, 2010). This review recommends that medication treatment be limited to patients for targeted symptoms only. Symptoms that appear to

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respond best to targeted treatment include anger and affective symptoms and cognitive-perceptual symptoms. Finally, in contrast to these two reviews, one study (Rinne et al., 2003) indicates that a patient’s particular characteristics may mean she will benefit from SSRI antidepressant use for emotion regulation. Patients with chronic PTSD and borderline personality disorder have been reported to have a better outcome with SSRI antidepressant treatment. Patients with a history of chronic childhood abuse in this study responded to the addition of fluvoxamine with decreased reactivity of the hypothalamic-pituitary-adrenal axis. This decreased reactivity results in a normalization of cortisol secretion, which is presumed to benefit cellular function in the hippocampus and amygdala and facilitate psychotherapeutic outcomes related to memory and emotion regulation. Applying these findings to clinical work leads to the following conclusions. First, don’t expect medications to effectively manage the overall severity of borderline personality disorder or to consistently work, even for targeted symptoms. Second, mood instability may respond better to mood stabilizers than SSRI antidepressants, unless the patient has a history of chronic PTSD or sustained childhood abuse. Although pharmacological treatment may have an adjunctive role in global symptoms of affective instability, impulsivity, and anger (Stephan, Krawitz, & Jackson 2007), the best evidence for effective treatment of borderline personality disorder is with psychological treatments. Medication treatment decisions for the personality disorder symptoms should be individualized based on the patient’s particular symptoms and the extent to which psychotherapy has been implemented.

Do Co-Morbid Symptoms Represent an Actual Axis I Disorder, or Are They a Manifestation of Borderline Personality Disorder? A substantial challenge in clinical work with patients with borderline personality disorder is to make a clear Axis I diagnosis in the face of the significant affective instability and cognitive dysregulation that are present. Co-morbid Axis I diagnoses are common. Patients with borderline personality disorder have a higher rate of bipolar disorder (both bipolar I and bipolar II subtypes) than patients with other personality disorders at initial diagnosis and a higher rate of new onset of bipolar disorder over a four-year follow-up (Walter et al., 2009). Patients diagnosed with borderline personality disorders have higher rates of mood disorders of all types; in one prospective series, 85% of patients had episodes of major depression (Gunderson et al., 2008).

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Substance use disorders occur in higher rates in patients with borderline personality disorder relative to patients with other personality disorders, even when the patient’s Axis II issues improve (Walter et al., 2009). Anxiety disorders are nearly as common as mood disorders (Zanarini et al., 1998), and, as Chapter 8 mentions, eating disorders are a frequent co-occurrence. Patient and persistent work to assess symptoms and historical data must occur in order to make the best determination of whether other co-morbid illnesses exist. If available and not previously performed, a formal diagnostic assessment (such as a SCID interview) may be extremely helpful in the decision-making process. One must be quite careful when assessing these patients diagnostically. The symptom assessment obtained by questions in structured interviews, such as the SCID, is far more specific and is designed to assess for diagnostic criteria in an efficient and accurate manner. Inquiring if a patient has “mood swings” is not an efficient strategy with respect to determining whether bipolar disorder exists under normal circumstances. In the patient with borderline personality disorder, this question will clearly not be helpful and can lead to an incorrect diagnosis. A particular danger is not diagnosing both disorders when bipolar disorder is present. Omitting the Axis II diagnosis may lead to a patient receiving only pharmacological treatment when she has a disorder that requires psychological remediation (Gunderson et al., 2006). Another tool that can help determine the significance of mood changes is to develop a timeline with the patient. A timeline of episodes and associated symptoms can be very helpful in sorting out the significance of particular symptoms and whether they cluster in a way that would indicate the presence of an Axis I diagnosis. The length of episodes is also very important to assess, since sustained and lengthy periods of elevated mood are uncommon in borderline personality in the absence of bipolar disorder. Developing a timeline is often a challenge, but it is worth doing. Such an exercise is similar to that used in working with bipolar patients to help them to identify prodromal symptoms more accurately. It is useful to ask the patient to use diaries, journals, calendars, and datebooks to serve as memory aides when these are available. If family members and friends can be helpful informants, this will add to the specificity of the diagnostic picture. A clinical assessment of interpersonal triggers for symptoms and the duration of a patient’s mood shifts can also be of critical importance. If the patient has a great deal of mood fluctuation, a careful behavioral analysis can help determine whether there were interpersonal situations (e.g., conversations, phone

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calls, and e-mail or text messages) that triggered the patient’s reactions. This is particularly important when assessing for an affective disorder. Automatic thoughts can be tracked that are associated with mood symptoms. Finally, both with the timeline and with behavioral analysis, external factors that contribute to vulnerability to mood shifts (such as substance use or poor self-care) can be traced and remedied, and added to the differential diagnosis. Finally, if the patient is working hard to acquire skills and is in effective psychotherapy with little relief from mood instability, care providers should have an increase in their suspicion for an Axis I mood disorder and assess again. Mood disorders commonly occur or reoccur in the course of borderline personality disorder. An alternative strategy, if no Axis I disorder is present and the patient is still struggling, is to consider treatment of the primary borderline personality associated mood symptom with medications, as described above. When a decision is made to prescribe medications to patients for borderline personality disorder and a coexisting Axis I disorder, it is optimal to have a clear understanding about the treatment plan. It is vitally important to convey realistic expectations about what medications can do to patients who have borderline personality disorder. If the expectation exists in the patient’s mind that medications will be the answer to the myriad of painful symptoms she has, at best she may be extremely disillusioned about medications. At worst, she may be prescribed numerous medications and potentially inadvertently develop dependence on them for “relief.” This is a situation that benefits from collaborative treatment with a prescriber who understands the biosocial model for the development of DBT and who can explain that there are limits to our capacity to provide pharmacologic relief for the pain of emotional dysregulation. Empathy and validation are key ingredients in these discussions with patients in this circumstance. It is helpful to acknowledge that the wish for an agent that “would make it all go away” makes sense, and equally helpful to point out that such a medication-based solution does not exist, even when medication helps. Optimal medication management of patients with borderline personality occurs in a stepwise and deliberate sequence, treating patients with one medication at a time whenever possible and allowing sufficient time to evaluate any benefits before changing medication. Orient the patient to this plan and to the reason for such an approach. It is helpful to have a written sequence of what you will try, of the symptoms that will be targeted, of the expected drug effects and when these will occur, and the typical time frame that is necessary

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for observation to see if positive results exist. Patients also benefit from knowing how they can help, for example, by using recording instruments to track symptoms. Since patients in DBT are accustomed to recording behavior on diary cards, they are often able to generate good suggestions for how they may best track and record data about their symptoms. In addition, the typical diary card also serves as a good monitor of medication adherence and symptom occurrence. The following patient example provides an illustration of this approach to the patient in pharmacotherapy. Marion is a 32-year-old woman who has struggled with a longstanding history of borderline personality disorder, alcohol abuse, and major depression. She was enrolled in a DBT program four months ago, after a hospitalization for a suicide attempt via wrist laceration when she was intoxicated. Marion has since stopped drinking and is attending Alcoholics’ Anonymous as well as DBT. She has a solid attachment to the program and for the first time has a sense of some developing stability. Unfortunately, Marion’s mood symptoms have persisted, and she has been evaluated by Dr. Baker, a psychiatrist who frequently consults to this DBT treatment program. Dr. Baker and Marion have determined that she meets criteria for major depression. They have discussed alternative medications and the pros and cons of each, and Marion has agreed that sertraline would be a good initial choice. The following conversation then took place. Dr. Baker: Okay, now that we’ve decided that sertraline is a good place to start, I wanted to find out what you knew about antidepressants and what you expect will happen when you start them. Marion: Well, I have taken them twice before, like I said. But it was never for very long, and never regularly. They did not seem to help when I took them. I was drinking a lot then. I know you are supposed to take them for awhile. I just thought they would calm me down more. Dr. Baker: Okay—lots of what you said is important. First, you are right, if you were drinking, it might not be possible for the medicine to help your mood as much. I know you are taking some steps to work on this, and that is terrific. The last time you tried the medicine, it might not have had the best chance to work. It is also absolutely true that if you do not take the pills every day for at least four to six weeks—after you are on the right dose—that we will not know if they work for you. I am sorry that this process involves so much

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Marion: Dr. Baker:

Marion: Dr. Baker:

Marion: Dr. Baker:

Marion: Dr. Baker:

trial and error, but it is the best we can do. And they do take a long time to work. The only reasonable way to go about this is for us to give you one medicine at a time, give it a long enough time to work, and evaluate how it works for you before we make a decision about changing it. Six weeks doesn’t seem worth it. Well, one way for certain that they won’t work is if you don’t take them for six weeks. (Marion laughs.) One difference this time, though, is that now you have your therapy appointment and skills training groups that can also help you deal with things in a different way when you feel badly until the medicine starts to help. That’s true. Seriously, though, my experience is not that after 42 days of misery that you will suddenly wake up and feel like a transformed person. First, antidepressants are not “happy pills.” If they were, I’d be even busier! The benefits begin gradually, and you are likely to notice some of them more quickly than others. Most people notice some benefit to their sleep and anxiety level after seven to ten days on a therapeutic dose. And their energy gradually begins to change after that. The last thing to improve for most folks is their mood. I wish it did not work that way, but that is the best we have right now. Okay. I can live with that. Two other things. One is that it is important for you to know that the anxiety reduction you obtain will only be the anxiety that you have that is associated with depression, not the anxiety that comes from emotion regulation problems—so you still will need to work on using tools to help with that feeling. And these pills will not work better if you take more of them or if you take them in response to feeling badly. In fact, they will make you feel worse if you do that. What do you think about trying to take them every day just at bedtime? I would like to try it. I’m wondering if you could keep a log of your sleep and energy level on your diary card as a way for us to monitor how much change there is for you over time. That will help us know what is working for you.

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CHALLENGES IN PRESCRIBING MEDICATIONS IN BORDERLINE PERSONALITY DISORDER Common problems that arise in combining medication treatment with psychotherapy in working with patients with borderline personality disorder include: 1. Balancing consulting to the patient and case management approaches when dual responsibility treatment involves a DBT approach 2. Poor communication in dual responsibility treatment 3. Polypharmacy 4. Time management and decision-making when a single provider both prescribes medication and is the primary DBT therapist 5. Countertransference A team approach to patients with borderline personality disorder can provide some of the most rewarding collaborations between disciplines—and can be the source of the most difficult ones. Establishing a reliable and respectful relationship with other care providers is critical to support efforts to keep the patient on track. When a consistent therapeutic framework is coupled with a collaborative and respectful working relationship, patients with this level of complexity are better served. DBT has promoted the value of a team approach to borderline patients, with the goal of improved outcomes through therapist consultation in an atmosphere of respect and the search for synthesis when conflict occurs. This type of relationship can exist between care providers who work in a non-DBT orientation—for example, between a CBT practitioner or a schema-focused therapist who manages a patient with borderline personality and who works in consultation with a psychiatrist. Clinicians prescribing for patients with borderline personality need to keep in mind safety and tolerability issues, as well as the potential for abuse. Patients with borderline personality disorder are prone to frequent suicide attempts, so one must prescribe medications with a low risk of lethality via overdose whenever possible. Unfortunately, because mood instability is frequently an issue, there is often an indication to prescribe anticonvulsant medications that are dangerous in overdose. Many patients with borderline personality disorder are exquisitely attuned to changes in their physiology, so particular attention must be paid to starting medications at low doses and

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collaboratively managing side effects. Finally, co-occurring substance abuse is frequent in this disorder and can make benzodiazepine or opiate prescription a challenge. It is critical to remember that this substance abuse or dependence may begin because the patient obtains relief from the exquisitely painful emotional states she has by taking these medications. This respite may be so reinforcing that the patient begins taking more medication than was prescribed. Patients need to develop skills to manage such symptoms. Physicians and therapists must provide an empathic and validating framework that acknowledges patients’ suffering rather than blaming them, but that also “does the right thing” with respect to prescribing medication that could be inadvertently harmful. A good example of such a conversation occurred between Marion and Dr. Baker at a follow-up visit. Marion had been improving on sertraline but was struggling with severe anxiety symptoms. She had an episode of “feeling as though (she) will explode with discomfort” when she was alone in her apartment. Marion: I think I need more medicine than this. I just can’t stand the way I feel when I am at home. I want to scream or throw things. I am so uncomfortable. I really need your help. Dr. Baker: It’s been really tough for you. What did you have in mind when you wanted my help? Marion: My old boyfriend used to give me his alprazolam when I felt this way. It just made a huge difference. I was hoping you would give me a prescription for that. Dr. Baker: Well, I can understand how that would make sense, given your experience with alprazolam. But the fact is that medicines have effects we want and effects we don’t want. And alprazolam has a large downside. First, it is addictive, and particularly so when you have a history of alcohol abuse. Second, it is a temporary fix for problems, and keeps you from trying other possible solutions. Marion: (tearful) I just feel so awful; don’t you see! Dr. Baker: I do see. And I wish there was an easy answer that really helped. On one hand you are miserable, I know. On the other hand, you need to practice some new ways that work to manage that. What skills are you working on in group and in therapy that might help us here?

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Marion and Dr. Baker talk about the distress tolerance skills she has learned. She agrees to try and use these over the next two weeks to see if they help her with her symptoms and then to revisit this with Dr. Baker. A shared-decision-making model, with all parties discussing the advantages and disadvantages of a particular medication approach, has been discussed as optimal for treatment of patients with borderline personality disorder (Stephan, Krawitz, & Jackson, 2007). Obviously, this model can only occur if the patient has the mental clarity to understand the consequences of a decision to use medication. In the presence of psychosis or severe substance abuse, this decision-making process may need to occur in a stepwise fashion, with the patient being provided informed consent about medication that can relieve her thought disturbance at that moment. Thereafter the patient can consider the wider range of modalities that could be beneficial.

Balancing Consulting to the Patient and Case Management Approaches When Dual Responsibility Treatment Involves a DBT Approach One very different and potentially contentious issue between a prescriber and a therapist working in a DBT model with a patient with borderline personality disorder is the DBT therapist’s strategy of consultation to the patient. Throughout this book, the premise has been that good collaborative care involves a team approach to the patient, with the therapist and prescriber sharing information freely and regularly regarding the patient’s condition. In DBT, under normal clinical circumstances, the therapist coaches the patient to communicate her history and needs to the pharmacotherapist directly, rather than communicating with the provider herself. There are important reasons for this treatment approach. The conceptual model for the development of borderline personality disorder in DBT involves a history of a pervasively invalidating environment that contributes to and maintains the problem. Therefore, a primary treatment philosophy of DBT is to communicate to the patient that she is an adult who has points of view and personal experiences that are valid, and that she has the capacity to make choices that will help her to build a life worth living. The latter point translates into the therapeutic stance when the patient is obtaining psychotropic medication that the patient is an adult who can reasonably navigate the process of obtaining medical care on her own and advocate for her own needs. Consultation to the patient conveys a respect for the patient’s

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capabilities (Linehan, 1993). The DBT therapist does not solve problems for the patient, but assists her in doing so on her own. This consultation to the patient approach is balanced with a case management approach that is similar to the approach to collaborative treatment presented in previous chapters—namely, that care providers collaborate and share information with the permission of the patient and with her full knowledge of what has been communicated. The case management approach is used in DBT when there is an immediate need to communicate with coproviders, when the lack of such communication may harm the patient, and when the patient cannot do this for herself. Examples of such circumstances could include communication that occurs after an overdose (if the patient is not conscious), or if the patient is unwilling to communicate life-saving information to a practitioner (such as the need to limit quantities of lethal medications available to her). The consultation to the patient approach has an additional benefit. Patients with borderline personality disorder have interpersonal skill deficits that need to be remedied by consistent practice. They need to develop the ability to manage themselves and their relationships with others. They need to practice assertiveness and tolerate the frustration that occurs in normal human interactions. Relationships with other treatment providers are good opportunities to practice these skills. The practice of consultation to the patient is frequently misunderstood by individuals who are unfamiliar with DBT as leaving the patient to “fend for herself.” This misunderstanding omits the possibility of the patient meeting with the therapist and prescriber in a team consultation meeting, and neglects the clear instruction to the DBT therapist to intervene when the patient cannot do so, or if the situation requires. A key principle articulated in DBT for borderline personality disorder is balancing two positions in an effort to help the patient. When, for example, there is an immediate need for a prescriber to know about a patient’s risk of substance misuse, or to be aware of a consistent pattern of polypharmacy that has interfered with a patient’s skill acquisition and employment, action must be taken to prevent harm to the patient or her treatment. Whenever possible, the patient is encouraged and her behavior shaped to help her communicate her needs herself, but if she cannot or will not do so, the therapist intervenes. The following clinical vignette is an example of consultation to the patient in clinical practice.

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Becky, a 28-year-old woman with a long history of borderline personality disorder, was in therapy with a DBT team. Ruth was her therapist. She was also receiving medication for bipolar disorder prescribed by Dr. Adams, a psychiatrist. Becky’s medication included lamotrigine, thyroxine, and bupropion. Becky came into her regularly scheduled therapy session and angrily said she “had had enough”; she was quitting her medication and not returning to Dr. Adams. Ruth asked Becky what led to this decision. Becky told her that Dr. Adams was disrespectful and never listened to her complaints. She said he also started all of his sessions with her ten to fifteen minutes late. The last straw was when Becky was late last week and he refused to give her additional time. Becky told Ruth she would just stop her medication if her primary care physician refused to provide it. Ruth validated that this situation certainly seemed frustrating and unfair. She asked Becky what she had tried to do about it. Becky said she just had not gone to her last appointment. Ruth observed that this might or might not have had any effect on Dr. Adams, and that it certainly would not let him know about what the problem was. In addition, Ruth pointed out it had the unintended effect of interfering with Becky’s medication and could destabilize her mood. Becky initially reacted to this with anger. She said, “He will never listen to me!” and accused Ruth of “taking his side.” On the contrary, Ruth said—she felt that Dr. Adams’s behavior was unprofessional and that Becky needed to be more effective in the relationship by presenting it as a problem to him. Ruth affirmed her respect for Becky’s wish to obtain another medication provider if this plan was ineffective, but said that the opportunity to be direct with Dr. Adams was too good to pass up, since Becky had a long history of problems with asserting her needs in relationships and they had identified this problem as something Becky needed to change in order to have a better life. Becky asked Ruth to call Dr. Adams for her. Ruth declined, but told Becky that they could brainstorm together about ways that Becky could learn to approach the situation. They eventually came up with the solution that Becky would bring the problem with Dr. Adams as something to work on in her skills training group, where she could problem-solve and practice alternative strategies. Ruth also offered Becky a telephone coaching session just before her next appointment with Dr. Adams. In this example, Ruth does not intercede for Becky, but, instead, validates the difficulty of the situation. She encourages Becky to use emerging interpersonal skills and supports Becky’s efforts. She helps Becky recognize the advantages of

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asserting her needs with Dr. Adams. She does not, however, call Dr. Adams to share what Becky can share for herself.

Polypharmacy Clinicians treating patients with borderline personality disorder must carefully monitor what medications are prescribed to the patient from all sources. Because patients with borderline personality disorder are perplexing and challenging for many physicians, the physicians may attempt to treat them symptom by symptom with multiple agents. In one study, such patients were taking more than two prescribed psychotropic medications, most frequently antidepressant and neuroleptic medications (Kolla et al., 2009). A scattershot approach to symptoms can be harmful. Insomnia, pain, and anxiety are common symptoms suffered by patients with borderline personality disorder; problems occur if these symptoms are treated in the same patient by a number of different physicians and psychiatrists who are unaware of each other. Polypharmacy can be dangerous for a number of reasons in this setting. It provides an easy route to obtain medications to use in overdose; it conveys to the patient that medication is the only way to respond to symptoms of affect dysregulation (and may therefore cause inadvertent problems with substance misuse); and it can produce numerous unwanted or dangerous side effects. Because of the difficulties patients with borderline personality have with interpersonal problems, they may jump from physician to physician over a short span of time and receive medications from each of them. Although frequent discussion of current medications and communication among providers can minimize this occurrence, ideally, coordination of care must respect the patient’s autonomy and capacity to communicate. The patient may need to be taught by her therapist that obtaining medical care by frequently changing providers is neither safe nor helpful. Another issue complicated by polypharmacy is the potential for patients to obtain a quantity of medications for an overdose. If the patient is hoarding medication for a possible suicide attempt, this should be treated as a life-threatening behavior by the DBT team. Since the therapist will see the patient far more frequently than the prescriber, in highly lethal patients there should be a plan in place that controls the amount of medication available to the patient, and the therapist must monitor adherence to this plan week-to-week in session. Ideally, this control over access to lethal means will occur because the patient communicates this need to the pharmacotherapist on her own.

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The following clinical example is a good illustration of how polypharmacy may occur and have a negative impact on a patient. Lorraine is a 42-year-old woman with borderline personality disorder. She is receiving medical care from a primary care physician, a cardiologist, a gynecologist, and a neurologist. She was referred to a DBT team for treatment after a hospitalization for “medication toxicity.” Ten days ago, she was found unresponsive by her husband and required a brief intensive care unit admission. Lorraine was being treated with temazepam for sleep and alprazolam for anxiety from her primary care physician. She received propranolol for tachycardia from her cardiologist. Her chronic pelvic pain was treated by her gynecologist with oxycodone. Lastly, she had trigeminal neuralgia (tic doloreaux) that was treated with carbamazepine. She mixed up the pill bottles one night after a long and upsetting argument with her husband. This resulted in an overdose of her medications. A frank and open discussion of the dangers of multiple medications must occur, with particular attention to validating the patient’s concerns and suffering. It is certainly true that an altered mental status may occur when a patient takes a number of different types of medications with inadvertent adverse consequences. It is extremely important to inform the patient that sometimes symptoms do not improve (whether we like it or not) with a pill, despite what the advertisements tell us. If patients are in dual responsibility treatment, it helps to make certain that both providers communicate with the patient about the expected targets of treatment with medications and psychotherapy, so that reasonable expectations of medication effects exist. Medication treatment and prescribers’ behavior can have many meanings to any patient, but may be particularly problematic in patients with borderline personality disorder. Prescribers unfamiliar with such patients must be educated to prepare to manage their emotional dysregulation if the prescriber refuses to accede to demands for particular types or doses of medications when these requests are counter to reasonable practice. Patients may experience such refusal as invalidating and react accordingly. Conversely, prescriber anger and labeling the patient as “drug-seeking” or “manipulative” rather than conceptualizing the patient’s behavior as an effort to obtain relief may escalate the patient’s instability. Clear and unambiguous communication from prescribers and therapists about the fact that emotional pain exists and is experienced by the patient can facilitate an alliance even when relief from such pain is not possible with a prescription.

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Primary care prescribers who provide pharmacotherapy must be educated about the ways to safely prescribe for patients with borderline personality disorder. Just as in affective and anxiety disorders, primary care physicians are often the first-line treatment providers for patients with borderline personality disorder. Unfortunately, primary care physicians also frequently provide benzodiazepine prescriptions for agitation and anxiety when patients are in distress, particularly when the patient has no history of substance use disorders. There are several problems inherent such a practice. First, patients can overdose on these medications (and also overdose on them in combination with other medications and compound the danger). Second, they can easily develop physical and psychological dependence on benzodiazepines, because of the painful emotional states that regularly exist in this disorder. Since most providers eventually become reluctant to renew or increase benzodiazepines, patients may subsequently resort to behaviors like lying, because they are desperate to obtain medication and consequently undermine their treatment and the relationship with their physicians. Third, the patient can quickly learn to use medications for relief rather than to use skills that they are learning or to tolerate discomfort when skills are ineffective. Educating the primary care prescriber about the dangers of prescribing benzodiazepine medications on a regular basis to patients with borderline personality disorder is an important part of collaborative care. Prescriber education can occur in several ways while preserving the therapeutic relationship with the patient and in accordance with the principle that the patient is her own best advocate. First, general information about DBT, if that is the mode of treatment that is being provided, can be sent to the practitioner. It is particularly helpful to explain what skills are taught to the patient as a part of DBT. Many practitioners unfamiliar with the model benefit from an understanding of the tools that patients will acquire in treatment and a general idea of the biosocial conceptualization of borderline personality disorder. The general information provided must include information about how communication between providers will occur. In DBT treatment, the general information should inform the pharmacotherapist that the primary communication will be with the patient, not with the collaborating therapist, and explain why this principle is employed. A second way to educate pharmacotherapy providers is to have a joint meeting between the patient, the therapist, and the prescribing physician, in which the issues relating to medication can be discussed and resolved. In these circumstances, the patient should be

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coached to take the lead and advocate for the care she needs. Generally, in primary care practices, these joint meetings are more easily held in settings where the behavioral health team is located in close proximity to the primary care physician’s office; alternative means can be used if this is too cumbersome (e.g., Skype or other type of video conferencing or speaker phone). Joint meetings are more easily accomplished in behavioral health settings, when the psychiatrist is in closer proximity to the DBT care provider.

Poor Communication Issues in Dual Responsibility Treatment Therapists who communicate with medication providers when collaborating in the care of a patient with borderline personality disorder must not assume that the practitioner, even if she is a psychiatrist, knows much about DBT or CBT in clinical practice. These treatments are relatively underemployed and their dissemination in psychiatric residency training is limited, and even more so in primary care residency training. It is necessary to find out what the provider knows and to offer to educate her about the DBT or CBT approach to the patient with borderline personality disorder. Specific elements to explain to the medication provider include your availability to the patient, the targets of treatment, and the approach to suicide crisis situations. Many providers will need the same type of education about managing suicide crises that families of patients who enter DBT require, particularly if they have always managed suicidal behavior by hospitalizing the patient. Learning a new way to conceptualize and approach such patients is often appreciated by providers who feel overwhelmed by the unrelenting chaos that they perceive in treatment. The assumption from DBT that the patient “is doing the best she can” is also helpful when applied to the other provider in collaborative treatment. Both providers have knowledge that will benefit the patient, but such knowledge must be offered and accepted. Increase your counterpart’s skill level by education and encourage an approach to the patient that is more consistent with yours. This can be enormously helpful and welcomed by a prescriber when he or she is less experienced in the DBT approach to such patients. When a prescriber is caring for patients with borderline personality disorder (whether a primary care practitioner or psychiatrist) and has primarily medication management skills at his disposal, he may employ them more frequently than is helpful to the patient. Better educated prescribers may employ validation and inquire about what skills the patient might use to manage emotional distress, refer the patient for telephone coaching, or maintain

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a problem-solving orientation with the patient. These practices will minimize polypharmacy and further reinforce the therapeutic paradigm. A related problem is that prescribers may also undertreat patients or avoid certain classes of medications (e.g., benzodiazepines or mood stabilizers) when it is possible that such medications would be quite useful because the prescriber is anxious about the patient’s potential for substance misuse or overdose. Consultation to the patient is complex in this particular circumstance; it requires that the therapist be informed about appropriate pharmacotherapy and that the prescriber is willing to listen. If such a patient is being treated in primary care, a good strategy may be to coach the patient to advocate with the primary care physician for specialty consultation with a psychiatrist. When such referrals are available, primary care physicians often welcome such a suggestion. When you are referring a patient with borderline personality disorder for a consultation, it helps to remember some of the principles discussed in Chapter 3. A clear understanding about the other practitioners’ principles of practice can help you find a coprovider who does not rush in to intervene in situations that are best handled by allowing the patient to use skills to manage herself. An example of this problem occurred in the initial part of Becky’s treatment with Ruth and Dr. Adams. Becky went to a medication management visit with Dr. Adams after a particularly difficult day at work. She had overslept the night before and was late for work. She had not had time to eat lunch because she left work early for the appointment. Just before she left work for her appointment, she had a public, verbal argument with one of her coworkers about which radio station she was playing in the office, and she was reprimanded by her boss because this was not the first incident of such behavior. Becky was tearful and angry at her appointment. She had no vegetative symptoms, no history of elevated mood, and no thought disturbances. Dr. Adams assessed the situation and increased Becky’s valproic acid and added lorazepam to quell her irritability. He did not inquire as to any other tools Becky might use to help herself, nor did he ask what events preceded the argument. Although Becky was in treatment for bipolar disorder in conjunction with her borderline personality disorder, there was no evidence that she was entering a manic episode. Dr. Adams responded to Becky’s irritability with medication, rather than referring her back to therapy to develop ways to be less vulnerable to her emotional states and to employ skills to manage her irritability and solve interpersonal problems.

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In addition to sharing treatment philosophy, the frequency and means of communication about the patient must be clear. If the patient is in DBT, this may involve three-way consultation meetings or telephone contact with the patient present, if direct discussion with the patient is insufficient. Patients who are not in DBT can also benefit from this approach to information-sharing, as it allows for clear and unambiguous communication with the patient as a part of the team, and respects and encourages the patient’s autonomy and skilled interpersonal communication. Understanding your counterpart in treating the patient can avoid significant differences in treatment approaches between providers that will be clear to the patient and may destabilize treatment. It is confusing and disruptive to care if one person on the patient’s “team” questions the value of the other’s approach with the patient. Another important issue to clarify is how the patient will access care in an emergency. Clarity about which provider should be called to address crisis situations is important. Patients with borderline personality frequently need access to providers in emergencies. Providers need to agree how to handle calls about suicide crisis situations and optimally agree on what criteria will signal the need for hospitalization. It is extremely difficult to determine when and for which patient with borderline personality the protection of an inpatient setting makes sense. When ideation is high, the urgency of the situation makes treatment decisions more challenging. Suicide is a traumatic event for therapists and prescribers alike. Fear of patient suicide can influence the action taken in a crisis without a careful consideration of the information each provider has about the patient. If practitioners do not share treatment philosophies, it is extremely helpful if they know how each will approach these particular patient concerns. This practice can avoid the possibility that a major difference in approach will unnecessarily complicate treatment. Lorraine and her DBT team confronted such difficulties early in her care. After Lorraine’s hospital admission for the medication overdose previously described, her relationship with her husband rapidly deteriorated. This was extremely upsetting for her. Although she was in individual therapy and had started DBT skills training, she was highly distressed and suicidal much of the time. She continued to call and visit her primary care physician to seek medications for relief, and told him that the DBT therapist “just doesn’t get how bad it is.” During one such conversation, she revealed the extent of her suicidal thinking. The primary care physician called the police, and Lorraine was committed to the hospital. This hospitalization was not effective in decreasing

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Lorraine’s suicidal thinking and did not further her skill development. In fact, the attending physician told her that her suicidal thinking was a result of a biological illness and that without an effective combination of medications, she would not recover. Lorraine spent several months seeking psychiatric treatment and received multiple combinations of medications, returning to DBT after she had no relief. When the prescriber is a psychiatrist, and the patient is in collaborative treatment, treatment roles must be clearly defined. Although the prescriber might know the patient exceedingly well, the prescriber must resist the temptation to provide other forms of psychotherapy in regular office visits for medication management. Therapeutic interventions about adherence, and adherence to therapy, are not included in this proscription. The patient needs to have a strong bond to the DBT team and a substantial connection to her primary therapist. That said, there may be situations when roles are clearly articulated, when providers share a similar treatment philosophy, and when resources are limited, when the prescriber can be a backup resource to the patient. This approach can be an effective and important source of support for the patient in urgent circumstances. An advantage of such a coverage arrangement is that a provider who knows the patient well and has a similar treatment philosophy can be available to the patient when the therapist is not. A disadvantage is that the patient and the psychiatrist may have difficulty when the therapist returns in transitioning back to a more limited role in which the psychiatrist only prescribes medication. Thus, clear and unambiguous discussions with the patient about the limited nature of such a coverage arrangement and the requirement for the patient to return to the primary therapist as soon as he is again available must occur before such an arrangement is made.

Time Management and Decision-Making When a Single Provider Both Prescribes Medication and Is the Primary DBT Therapist Standard DBT does not advocate for psychiatrists (or nurse practitioners) providing both therapy and medication to patients. Collaborative care is regarded as optimal patient management. This idea is counter to a number of recent recommendations in the psychiatric literature that propose that the optimal choice for such patients may be a single provider (Gabbard & Kaye, 2001). The position that standard DBT proposes has a similar intention to the separation of medication and therapy providers in earlier psychodynamic literature—that is, the therapeutic relationship is best preserved when a

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different provider handles each part of the patient’s care. There is not an evidence base to draw upon for either approach. There are circumstances when, by necessity or choice, the patient has a single provider. Should this be the way treatment is structured, the patient and provider need to frankly discuss a treatment agreement that includes the possibility of the patient being referred elsewhere if there are power struggles about medication or if medication issues supplant the primary tasks of therapy. Frankly, the time constraints when one person provides both treatments are substantial. It is extremely difficult in one session to both attend to assessment and management of pharmacotherapy and provide psychotherapy in such complex patients. Time limitations may require the patient to be seen more frequently than once per week, and to specifically delineate time for each purpose. Additionally, providing both interventions requires much more time for the provider to be thoughtful about what treatment is appropriate. On one hand, patients struggling with emotion regulation desperately want relief and frequently misuse or seek pharmacological means to obtain relief. On the other hand, Axis I disorders that can be effectively targeted with medication are prevalent in this group of patients. And as the previously cited literature indicates, targeted pharmacotherapy can be helpful to address some of the painful symptoms that patients experience. When the patient is being managed by a single provider, the complexity of this decision coupled with the intensity of the interaction with the patient requires the provider to obtain frequent DBT team consultation to make the best decisions possible. And because the provider has the power to prescribe or withhold medications, the relationship may be affected by this. Patients may be less forthcoming, and practitioners may develop “blind spots” regarding the best treatment.

Countertransference Countertransference issues can be a particularly problematic in dual responsibility treatment with borderline patients. First of all, patients with chronic suicidal behaviors engender an enormous amount of anxiety in their caregivers. Prescribing physicians are often concerned that they have more legal liability in a collaborative treatment arrangement and therefore become concerned about the “lack” of intervention by DBT therapists (as they see it) when patients make suicide attempts. Practitioners who are poorly educated about DBT or who do not typically work in collaborative relationships or who take a more authoritarian role with patients and other mental health

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providers may be more prone to this point of view. A good strategy to avoid this circumstance is to use the techniques discussed in Chapter 3 to find your referral base and make certain that you provide substantial education in the collaborative care relationships you have. Another problem with respect to countertransference is when prescribers or therapists working with such patients automatically assume that certain behaviors are conscious “manipulation” by the patient or a sign that the patient is “too sick to be helped.” Patients who are struggling with borderline personality disorder employ strategies and behaviors that have a function. Determining what that function is, and substituting more effective or less damaging behaviors, are important goals of treatment. Blaming the patient for behavior that is working is not likely to yield good results. Hence, the concept of “splitting” providers may be reconceptualized as providers having different reactions to a difficult patient, and the patient responding to those reactions to fulfill a particular need. When a patient with borderline personality disorder communicates negatively about the other care provider, it is an opportunity to help her to employ interpersonal skills to negotiate a better relationship with the other provider. However, if serious complaints occur (e.g., allegations of ethical or sexual misconduct or gross deviations from reasonable standards of practice), they must not be ignored. The therapist or prescriber must investigate by privately questioning the other provider. Patients with borderline personality disorder are disproportionally represented in those patients with whom care providers become sexually involved, for example (Galletly, 2004), so it requires our attention when such serious information is communicated. Collaborative treatment in patients who have borderline personality disorder is without question one of the most challenging clinical situations practitioners face. There are many reasons to be optimistic about current treatment and future developments in working with this group of patients. Treatment development for borderline personality disorder has made great progress. More effective tools and strategies are available to us, and research to find better treatment is more popular as a result. Hopefully, research about combined treatment in this vexing problem will help us be better able to provide efficient and successful care to patients who are truly suffering.

Combining CBT and Medication: An Evidence-Based Approach by Donna M. Sudak Copyright © 2011 John Wiley & Sons, Inc.

CHAPTER

11 Combined Treatment in Pregnancy OVERVIEW More than two care providers are mandatory when psychiatric disorders occur during or after pregnancy. Mental health providers must work collaboratively with the patient’s obstetrician and the baby’s pediatrician to get the best results. Women who have preexisting psychiatric conditions and who are taking psychotropic medication benefit from frank and open discussions with their treatment providers regarding the impact of their condition on pregnancy and the risks of the postpartum period. The safety (or lack thereof) of medication treatment during pregnancy is also important to review. Problem-solving, planning for pregnancy, and informed decision-making are extremely helpful for the family-to-be. Ideally, the decision to take medication during pregnancy is one that should be made in an atmosphere of thoughtful, informed consent, with both the patient and, when available, her partner. Even in such circumstances, there is an enormous amount of unpredictability in the process of conception, pregnancy, and delivery, regardless of whether a mental illness is present. Coupled with this unpredictability is the increased frequency of symptom reoccurrence in patients who have a preexisting psychiatric disorder who become pregnant. Patients frequently do not have discussions about the effects of medication before they become pregnant, which can mean that anxiety can permeate pregnancy and exist during their children’s development. Because our knowledge about drug effects in pregnancy is limited, this chapter will not provide a review of each psychotropic drug class in pregnancy. It is nearly impossible to do this because of the constantly changing information available 181

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about psychotropic drug effects on infants born with prenatal exposure. It will instead provide general principles to guide clinical practice when working with patients who are pregnant or contemplating pregnancy and some specific data that is known about particular drug classes. Each patient’s medication regimen should be evaluated on a case-by-case basis when pregnancy is contemplated or discovered to determine the most recent information available about drug safety. There are several sources of information to consult, in addition to published material, such as the Physicians' Desk Reference. The American Academy of Pediatrics and the American College of Obstetrics and Gynecology (ACOG) publish periodic review articles regarding the retrospective and prospective data that exists about medication use in pregnancy (American Academy of Pediatrics, 2000; ACOG Practice Bulletin, 2008). Advising prospective mothers treated with psychotropic medications is complicated by the fact that some medications prescribed (lithium, for example) have specific data regarding teratogenic effects, while others (e.g., SNRI antidepressants) have much more limited information. In addition, as a recent article describes, “Even when evidence-based decisions are made, clinicians and patients are often faced with data that is inconsistent with prior data” (Burt, Bernstein, Rosenstein, & Altshuler, 2010).

PRINCIPLES OF MANAGING PREGNANT WOMEN WITH PSYCHIATRIC DISORDERS Providing No Treatment for Psychiatric Illness Also Has Risks for the Baby An important principle to remember when working with women contemplating taking psychotropic medication during pregnancy is that untreated illness also has a significant impact on the fetus. Untreated depression, for example, is an independent risk factor for problems with fetal development. Maternal depression can mean poor adherence to routine prenatal care and less good outcomes for mothers and infants. Infants born to depressed mothers who are untreated have more postnatal irritability and anxious and withdrawn behaviors in early childhood (Oberlander, Warburton, Misri, Aghanjanian, & Hertzman, 2006). Untreated major depression adversely impacts maternal-infant bonding (Lovejoy, Graczyk, O’Hare, & Neuman, 2000). Children whose mothers are depressed have a future risk for neurodevelopmental problems, including delayed language development and lower IQ scores (Sohr-Preston & Scaramella, 2006). They

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also exhibit more sleep problems and a higher risk of mental and medical illnesses (van den Bergh, Mulder, Mennes, & Glover, 2005). In addition to retrospective data, an important study by Wisner and colleagues (2009) prospectively determined that untreated major depression is a risk factor for preterm delivery and lower birth weights. The mechanism postulated for adverse effects on development in untreated depression is that fetal development occurs in the presence of increased levels of maternal adrenal (stress) hormones (Talge, Neal, & Glover, 2007). Major depression has been the best studied illness because it is so prevalent in women during the period of highest fertility (Weissman & Olfson, 1995). One would assume that the risk of preterm delivery and lower infant birth weights exists in other psychiatric illnesses if the mechanism that produces the problem relates to stress hormones. Population-based studies comparing mothers with schizophrenia also show that both typical antipsychotic medications, as well as pregnancy in schizophrenic women who are not medicated, are associated with preterm delivery (Lin, Chen, Chen, Lee, & Wu, 2010).

Psychiatric Illnesses Do Not Abate During and After Pregnancy Pregnancy does not convey protection against depression or anxiety disorders, as once was commonly believed. Although percentages vary, studies indicate that approximately 10 to 15% of women have mood or anxiety disorders during pregnancy, for example (Evans, Heron, Francomb, Oke, & Golding, 2001). Women with preexisting psychiatric illnesses who are on medication and who become pregnant have a double burden of risk for exacerbation of their symptoms if they are withdrawn from medication rapidly because of the stress of pregnancy (both psychological and neurochemical) and because abrupt medication discontinuation is more likely to produce recurrence in affective and anxiety disorders (Baldessarini, Tondo, Ghiani, & Lepri, 2010). In illnesses such as schizophrenia or bipolar disorder, these consequences are particularly important—and in bipolar disorder, there is the potential risk of converting to the rapid-cycling form of the illness as a result of both pregnancy and medication discontinuation. Patients who are bipolar who discontinue mood stabilizers rapidly have a greater risk of relapse and of the development of suicidal ideation (Faedda, Tondo, Baldessarini, Suppes, & Tohen 1993). In bipolar patients, optimal management may entail a slow taper of lithium and/or other anticonvulsant mood stabilizers prior to attempting conception and the use of second-generation antipsychotic medications to stabilize mood during the first trimester of pregnancy.

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Combined treatment may be an enormous benefit when women have a history of prior psychiatric illness and want to discontinue medications to become pregnant. CBT can attenuate relapse risk in patients with depression and anxiety disorders who have recovered on medication, as discussed in Chapters 5 and 7. One study of depressed women who discontinued medication during pregnancy reported a 68% risk of depression relapse (Cohen et al., 2006). CBT can provide significant relapse protection when depressed patients want to stop medication in order to conceive but not incur the risk of untreated depression or medication exposure to their infants. Another advantage of CBT for pregnant women is that a major focus of treatment is teaching patients to use the tools of treatment independently and to use practical problemsolving approaches to life events. This could benefit them in the future, when they encounter stressful life events. Pregnant women with a history of depression are known to have a higher risk of postpartum depression. One study (Rahman, Malik, Sikander, Roberts, & Creed, 2008) used rural health workers to administer seven sessions of community-based CBT to depressed pregnant women on no medication. Patients were randomly assigned to CBT or enhanced routine care to account for the extra time spent with health workers. At six months postpartum, 53% of the group who did not receive treatment met criteria for depression, and only 23% of the group who received treatment met criteria. These results were sustained at 12 months, and were accompanied by better maternal functioning and child health. This study supports the idea that there are benefits to CBT in pregnant depressed patients with respect to postpartum symptoms as well as during pregnancy. Women who do not respond to CBT could benefit from IPT, which has also been shown to be beneficial in pregnancy (Clark, Tluczek, & Wenzel, 2003). Because CBT for anxiety disorders is also highly effective, it may benefit pregnant women with anxiety who wish to discontinue medications, as well.

CLINICAL APPROACHES TO WOMEN ON PSYCHOTROPIC MEDICATION WHO WISH TO BECOME PREGNANT Advising Women About Pharmacotherapy The decisions facing women with mental illness who are pregnant or wish to become pregnant are complex and therefore warrant both time and careful

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consideration. Optimal care of women in their childbearing years should include a discussion about their thoughts about future childbearing, their understanding of the effects of childbearing on her illness, and education about such effects when indicated. Women who are on psychotropic medications should be asked about contraceptive use, and instructed that the best management of potential pregnancy is to discuss the pros and cons of remaining on medication and have a plan before conception occurs. The decision to remain on medication or to discontinue it must be informed by the particular psychiatric history of the patient, the medication used, the severity and type of previous symptoms, and any history of suicidal or violent behavior. The patient’s support systems, her preferences, and her partner’s preferences and cultural expectations are all important areas to explore—ideally, in advance. Practitioners can facilitate this by making discussions about future childbearing a routine part of the management of women of childbearing age. A helpful way to discuss the risk of exposure to psychotropic medications is to divide the risk into specific time periods in the life of the developing infant. These risks include the risk of teratogenicity, the risk of altered growth, the risk of neonatal toxicity and withdrawal, and the risk of problems with neurocognitive development later in childhood. Breastfeeding is another area of concern that must be addressed. Each medication class and each individual medication conveys a unique risk to the baby. All psychotropic medications cross the placenta, all are present in the amniotic fluid, and all are found in breast milk. Electronic resources exist to help clinicians with the most updated information about reproductive toxicity, such as http://www.reprotox .org and http://depts.washington.edu/terisweb. When discussing risk with patients, one must check the most current information about medication at the time of the discussion because so little information is available for many psychotropic drugs, and data is constantly added that can impact the patient’s decisions.

Teratogenicity Teratogenicity is abnormal fetal development that occurs because patients take medication during fetal organogenesis. Because fetal malformations also occur in the absence of such exposure, and because individual case reports are the source of data for most drug toxicity, it takes time to determine an absolute association between drug exposure and fetal malformation. Often, other uncontrolled exposures (for example, alcohol or illicit drug use) can

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occur in conjunction with fetal exposure to psychotropic medications and confound results. Nevertheless, we are aware that many psychotropic medications are associated with teratogenesis—lithium, for example, is associated with significant cardiac malformations when first trimester exposure occurs. Teratogenic dangers to the baby are time-limited—once organs are formed, then medications can be safely given with no further danger of fetal malformations. Because teratogenicity is confined to early pregnancy (the first trimester), women of childbearing age taking medications must be given frequent reminders about not becoming pregnant accidentally so that unintended risks do not occur. In addition, we must help patients who inadvertently exposed a fetus to psychotropic medications make sense of the actual risk for malformation and how it compares to the risk of spontaneous malformations to help them determine the best course of action. This process is ideally done in conjunction with the patient’s obstetrician. The following case example is a good illustration of managing a patient who takes antidepressants during early pregnancy. Jane is a 25-year-old married woman who has been taking citalopram for recurrent severe depression. Jane was hospitalized twice in her early 20s for suicidal ideation and debilitating symptoms. She recovered without incident and has been managed by her primary care physician. Jane recently discovered she was six weeks pregnant. She and her husband, who is a paramedic, have always wanted children. She made an emergency appointment to see Dr. White, a psychiatrist, and asked to come in with her husband. Jane’s husband was very concerned that Jane had been on antidepressants. They had not discussed the question of what to do about her medication prior to any attempts to conceive. Jane is terrified about stopping her medication and going back to the hospital. Dr. White reviewed the data about the use of SSRI antidepressants during the first trimester with Jane and her husband during the initial visit. They were both quite relieved by the fact that many SSRI antidepressants have a long history of use during pregnancy, and that first trimester exposure to citalopram does not impart a known substantial risk to the baby’s physical development. Neither of them was aware that Jane’s depression itself could be a risk to the baby, if it reoccurred. Furthermore, Jane has not had any therapy since her discharge from the hospital. Dr. White suggested trying a course of CBT and discontinuing her citalopram with close monitoring if Jane and her husband decided they would like her to see if discontinuing medication is possible.

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Fetal Growth Another risk factor imparted by some psychotropic medications is poor fetal growth. Fetal growth retardation has adverse consequences to the infant and is related to maternal weight gain. Fetal growth is adversely effected by late continuous exposure to SSRI antidepressants (Chambers, Johnson, Dick, Felix, & Jones, 1996). Mothers who take SSRIs in both the second and third trimester have babies with lower birth weights, and they are more frequently delivered preterm (Wisner et al., 2009; Oberlander et al., 2006). An obvious way that combined treatment can benefit patients in this circumstance is to make everyone aware of the need to monitor and promote maternal weight gain. If a patient chooses to do so, she can also attempt to taper medication and see if CBT can assist her in preventing the reoccurrence of symptoms.

Neonatal Syndromes Neonatal syndromes are medical or behavioral manifestations that occur in infants who have been exposed in utero to medications. Neonatal syndromes are also known to occur in patients with untreated psychiatric disorders. An example of a neonatal syndrome is contained in the Chambers study (Chambers et al., 2006) that found that infants exposed in utero to paroxetine after 20 weeks’ gestation had a 6 times greater risk of primary pulmonary hypertension compared to unexposed infants. Despite the fact that this event was relatively rare, primary pulmonary hypertension is potentially fatal. This consequence should inform decisions about which SSRI antidepressant to use, if one is needed during pregnancy. In addition, Chambers and colleagues (1996) described that one in three infants exposed to any SSRI antidepressants developed a syndrome of transient neonatal behavioral distress. Other neonatal symptoms that occur after late-term exposure to SSRI antidepressants include respiratory distress, tremor, sleep problems, jaundice, and feeding problems (Moses-Kolko et al., 2005; Oberlander et al., 2006). These adverse events typically do not require medical treatment, but longer hospital stays and more special care admissions do occur in exposed infants. Other psychotropic medications are also associated with neonatal syndromes. When medication is continued, the pediatrician or neonatologist becomes part of the team caring for the family. These postnatal events must be a part of the risk/benefit discussion about continuing medication during pregnancy; with the knowledge that other authors (Misri et al., 2004)

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have noted that babies born to mothers with untreated depression also have more difficulty with neonatal adaptation. Therefore, just as with the risk of low birth weight and preterm delivery, depression and medication exposure are each independent risk factors for transient neonatal syndromes. Discontinuing medication and staying well imparts a different risk to the infant than discontinuing medication and having a recurrence of the illness.

Neurocognitive Development Exposure to psychotropic medications or psychiatric illness has long been a concern as regards the neurocognitive development of the young child. Several small studies exist about particular medication exposure and subsequent neurocognitive child development. For example, studies of gestational exposure to SSRI antidepressants indicate that in exposed children, by four to five years of age the transient neonatal syndrome of decreased affect in early infancy observed by some groups of researchers is gone. Misri and colleagues (2006) observed no increase in anxiety, depression, emotional reactivity, or somatic symptoms in young children with in utero SSRI antidepressant exposure. Nulman and colleagues (2002) in a prospective, controlled study found no indication of any adverse neurodevelopmental consequences of prenatal SSRI antidepressant exposure. IQ scores, temperament, mood, activity, behavioral, and language development were similar in children with prenatal exposure to fluoxetine, tricyclic antidepressants, and controls with no exposure (Nulman et al., 1997). Because these are studies with small sample sizes, further prospective follow-up of the development of children exposed in utero to both psychiatric illness and psychotropic medication is warranted.

Risk of Untreated Psychiatric Illness for the Mother In addition to the risks enumerated for the unborn baby, particular risks exist for a pregnant woman with untreated mental illness. The obvious risks include suicidal thinking or behavior, suicide, poor self-care, and debilitating symptoms with psychosocial consequences. Bipolar disorder is a particular problem because of the possibility that it can change to a more malignant form of the disorder during pregnancy. Women who develop mental illnesses during childbearing sometimes contend with both the illness and shame about it, because it occurs during a time that is supposed to be joyful. This shame can lead to underreporting of symptoms. Family members and friends may minimize the patient’s symptoms (i.e., “She’s just moody because she is pregnant”) or blame

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the patient for her lack of excitement about the pregnancy. Mental illness is seen as a moral failing in many cultures and subcultures, further burdening the mother. Prenatal care and adequate nutrition suffer when a pregnant woman struggles with mental illness. Any woman who has depression during pregnancy has a higher risk of postpartum depression, which can adversely impact her ability to care for herself and her children and put her marital relationship in jeopardy. Women with a history of psychiatric diagnoses also must contend with the concern that they may genetically predispose the baby to the same problems. Despite these concerns, many women with psychiatric illness want to have children, and the positive results of effective treatment mean that many women who were previously seriously impaired now recover sufficiently to want a family. This desire is reasonable and requires us to sensitively discuss the options and risks. When the patient chooses to discontinue medication, a good strategy is to evaluate and employ potential alternative treatments available and plan targets for changing levels of care.

Managing Psychotropic Medications Use During Pregnancy Optimal pharmacotherapy during pregnancy is the use of the least toxic drug to the baby, at the minimal effective dose, avoiding the first trimester whenever possible. Combining CBT and medication treatment has the potential to yield more positive outcomes in this circumstance. Patients may be able to manage symptoms more effectively on less medication with the tools of CBT. When medications are needed, the obstetrician should be a part of the team, monitoring maternal weight gain and fetal growth and development. Communication about the pregnancy should extend to the treatment team. When the patient is close to delivery, plans should be made regarding possible postpartum exacerbation and breastfeeding, and a neonatologist should be consulted, if appropriate. An example of an early treatment plan for a patient who chooses to continue medication is Sally, whose bipolar disorder has been managed with lithium. Sally is a 32-year-old woman with a history of bipolar disorder, type II. She has been hospitalized with two suicide attempts, one of which involved a severe overdose that required ICU admission. She has been stable on lithium since age 27. She and her partner have decided they want a child. Sally has discussed the fact that lithium has a risk of significant teratogenic risks early in pregnancy. Neither she nor her partner is willing to risk this

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occurrence, or to screen for cardiac malformations in the baby and terminate the pregnancy. She accepts the possibility that she could develop rapid-cycling symptoms if she stops lithium. Her severe symptoms have always been in the depressive spectrum. She wants to stop medication. Sally and her partner establish a plan with Dr. Wood, Sally’s psychiatrist, that includes weekly CBT visits and mood monitoring. If Sally develops more significant depressive symptoms, she plans to increase behavioral activation; and she agrees that if it is unsuccessful, she will go to a partial hospital program to increase her structure until she passes the first trimester, when she plans to restart the lithium. Furthermore, she agrees to be hospitalized if she develops suicidal thinking or signs of mania. Sally also agrees to consider starting a second-generation antipsychotic medication for mood stabilization should this be warranted during the first trimester.

Postpartum Screening An important aspect of caring for patients with mood disorders is informing them about the risk of postpartum depression and explaining that particular symptoms should not be ignored after delivery. Patients who are well informed can be treated early and avoid significant consequences. Postpartum depression has significant consequences to the infant and young child, including problems with maternal-infant bonding (Murray et al., 1996) and interference with childhood cognitive development (Sharp et al., 1995). Patients may be able to use skills learned in CBT to attenuate some postpartum symptoms, as shown in the Rahman study (2008). Patients with a history of major depression or bipolar disorder, or who have had depression during pregnancy, should be more frequently screened for symptoms of postpartum depression after delivery because they have a higher risk for developing the disorder. For example, patients with a history of major depression are twice as likely to have postpartum depression as women in general, and patients who are depressed during pregnancy are roughly three times as likely to have such symptoms. CBT is effective treatment for postpartum depression, as are interpersonal therapy (IPT)(Clark, Tluczek, & Wenzel, 2003) and medication. CBT and IPT have the advantage of not impacting breastfeeding, unlike medication. Postpartum psychosis is a far rarer event, occurring in about 0.1% of women after childbirth. Postpartum psychosis is a psychiatric emergency that requires inpatient care. Patients with bipolar disorder are particularly vulnerable to postpartum psychosis. It is possible to prevent it in such patients by reinitiating lithium

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treatment no later than 48 hours after delivery. Sally, who discontinued her lithium in order to conceive, provides a good illustration of the management of patients in later pregnancy with regards to medication treatment. Sally discontinued her lithium treatment, and in three months, she was able to conceive. She had an uneventful first trimester and the baby was developing normally. Sally made the decision to wait to restart lithium treatment, because things were going well and she thought it would be better for the baby if she could avoid the medication. In the second trimester, Sally began to struggle with insomnia, which was an uncharacteristic symptom for her. She used exercise, sleep hygiene measures, and meditation to try and cope, with some good results at first, but by the 30th week of pregnancy she was sleeping approximately 6 hours per night. Sally began to develop significant irritability. She did not have any other symptoms of mania or depression at that time. Dr. Wood met with Sally and her partner to discuss again the risks and benefits of medication treatment and to plan for delivery and the postpartum period. Sally had found out that her mother had had postpartum psychosis that required hospitalization after Sally’s birth. She was unaware of this before her pregnancy, because the family had kept it a secret. Dr. Wood discussed the risk of postpartum psychosis with Sally and her partner, and also discussed her concern about Sally’s current symptoms. Sally admitted to having distractibility and racing thoughts that she attributed to the stress of pregnancy. She and her partner decided that her best course of action would be to restart her lithium now and continue it postpartum, even if that meant she could not breastfeed the baby.

Managing Breastfeeding As Sally’s example illustrates, women who are taking medication require counseling about breastfeeding. Breastfeeding has benefits to the infant that require a discussion of the risks of potential drug exposure versus these positive effects. The age and health of the infant also are factors that must be considered in the discussion; babies who will be exposed to drugs in breast milk must have healthy and mature organs to metabolize them. The literature about breastfeeding and exposure to psychotropic medications in breast milk is similar to the literature about pregnancy—data is available from single case reports or very small series of cases to inform our advice to the patient (Kohen, 2005). Psychotropic medications are detected in infant blood samples from mothers taking medication who are breastfeeding (American Academy

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of Pediatrics, 2001). These blood samples indicate that many medications pass in breast milk to the infant, but frequently in very small or barely detectable quantities. Again, there is little to no data to help us determine what this means for infant development. Available information suggests that no serious consequences of SSRI or tricyclic antidepressants exist during breastfeeding. This is not the case with lithium and clozapine, which are contraindicated during breast feeding. Individualized treatment plans are critical, and should occur prior to delivery. Genetics, maternal stress, and pre- and postnatal medication exposure all impact the development of a child born to a mother with mental illness. Combining CBT with medication or using CBT as an alternative to medication has the potential to attenuate some of the risk factors faced by mothers and children in this challenging circumstance. Active and direct discussion early in treatment with women sets the stage for continued dialogue about effective treatments and early management of symptoms during pregnancy and after delivery.

Combining CBT and Medication: An Evidence-Based Approach by Donna M. Sudak Copyright © 2011 John Wiley & Sons, Inc.

CHAPTER

12 Combined Treatment for Substance Abuse and Dependence Written with Samson Gurmu, M.D.

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lcohol and drug misuse are widespread, often refractory illnesses which frequently are underreported and undertreated. These conditions complicate the management of other psychiatric conditions. Many clinicians are frustrated by the often chronic, relapsing nature of addiction and struggle to find effective methods to manage such patients. The purpose of this chapter is to describe the medications that exist to assist in the clinical management of alcohol and drug addiction, to review evidence about combining CBT interventions with medication in these conditions, and to briefly discuss several particular challenges in working with such patients, namely, co-morbid psychiatric illness, pregnancy, and co-morbid HIV and hepatitis C infection.

OVERVIEW Addiction is a chronic, often relapsing brain disease that causes compulsive substance seeking and use despite harmful consequences to the individual who is addicted and to those around them (National Institute on Drug Abuse, 2009). Drug- and alcohol-related problems are among the most frequent problems encountered by mental health practitioners in the United States. According to the 2009 National Survey on Drug Use and Health, an estimated 21.8 million Americans age 12 or older were current illicit drug users (Substance 193

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Abuse and Mental Health Services Administration, 2010). This estimate represents 8.7% of the U.S. population in this age range. In the same survey, an estimated 22.5 million people were classified with substance dependence or abuse, roughly 9% of the population in this age range. Of these, 3.2 million were classified with dependence on or abuse of both alcohol and illicit drugs, 3.9 million were dependent on or abused illicit drugs but not alcohol, and 15.4 million were dependent on or abused alcohol but not illicit drugs. The lifetime risk of developing alcoholism in the United States is more than 15% for men and between 8 and 10% for women, which makes alcoholism one of the most common psychiatric conditions. Multiple national surveys have consistently indicated that drug- and alcohol-related problems are disproportionately higher among young adults, minorities, the poor, and those with lower educational status. The economic cost of substance abuse in the United States, factoring in health costs, crime-related costs, and loss of productivity, exceeds half a trillion dollars each year (Office of National Drug Control Policy, 2004; Centers for Disease Control and Prevention, 2005; Harwood, 2000).

EVIDENCE FOR THE USE OF MEDICATION FOR SUBSTANCE USE DISORDERS Psychotropic agents are frequently utilized in patients suffering from substancerelated disorders to address persistent psychiatric symptoms from co-morbid conditions such as depression and anxiety, which may indirectly contribute to continued substance use. This section of the chapter will review medications that are used to directly reduce drug or alcohol consumption. In recent years, the Food and Drug Administration (FDA) has approved several new drugs for the treatment of substance use disorders.

Medications Used in Alcohol Dependence There are three medications approved for the treatment of alcohol dependence: disulfiram (Antabuse®), naltrexone in an oral (Revia®), and long-acting form, (Vivitrol®) and acamprosate (Campral®). In addition to these FDA approved medications, there is a growing interest in using anticonvulsant medications such as topiramate and carbamazepine for the treatment of alcohol dependence (Mueller et al., 1997; Johnson et al., 2008). The use of pharmacotherapy in substance use disorders and specifically in alcohol dependence could be conceptualized as biologically enhancing mechanisms of either external or internal

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control. For example, disulfiram, as an “aversive agent”, would enhance external control by punishing alcohol use. On the other hand, medications that affect the endogenous reward system, such as acamprosate or naltrexone, could be assumed to bolster internal control because they block the positive and negative reinforcement of substance use (e.g., the pleasure of use and the relief from craving associated with use, respectively). Of note is that this chapter uses the words alcohol and ethanol interchangeably.

Disulfiram Disulfiram is an alcohol (ethanol) sensitizing agent or an aversive agent that alters the body’s response to ethanol, thereby making the ingestion of ethanol unpleasant or even toxic. It is the only alcohol sensitizing agent that the FDA has approved for the treatment of alcohol dependence. Disulfiram inhibits the enzyme aldehyde dehydrogenase in the liver, which is responsible for the conversion of toxic acetaldehyde, a breakdown product of ethanol, to acetic acid. Ingesting alcohol while this enzyme is inhibited elevates the blood acetaldehyde concentration. Thus, a person taking disulfiram, or within a week of discontinuing disulfiram, will have a disulfiram-ethanol reaction (DER). The symptoms and signs of a disulfiram-ethanol reaction include warmness and flushing of the skin, increased heart rate, palpitations, decreased blood pressure, nausea, vomiting, shortness of breath, sweating, dizziness, blurred vision, and confusion. While most DERs are self-limited, lasting approximately 30 minutes, severe reactions can occur. The severity of such reactions is mediated by the dose of disulfiram and/or the quantity of alcohol ingested, and can be life-threatening. Thus, the utility of disulfiram in the treatment of alcohol dependence lies in the potential to discourage individuals from ingesting alcohol because of the knowledge that this reaction will occur. Disulfiram use is commonly associated with a variety of adverse effects, including drowsiness, lethargy, and fatigue. Rarely, it may be associated with optic neuritis, neuropathy, and liver toxicity. The approval of disulfiram by the FDA (1951) for alcohol dependence predates the implementation, by the agency, of rigorous requirements for efficacy that must now routinely be satisfied for a medication to be marketed. In 1971, 20 years after it received approval as a treatment for alcoholism, a review of the existing literature on the efficacy of disulfiram concluded that only one of the more than 40 studies met adequate research design criteria (Lundwall & Baekeland, 1971). Half

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a century later, a review of 135 research studies using disulfiram found out that only 5 were controlled clinical trials with oral disulfiram (Garbutt, West, Carey, Lohr, & Crews, 1999).

Naltrexone Naltrexone, a drug used in opiate addiction, is also approved by the FDA for alcohol dependence. It is an opioid antagonist. Naltrexone is assumed to work in alcohol dependence by blocking the “priming effect” of alcohol on the endogenous opioid system and subsequently decreasing the euphoric effects of alcohol. This in turn makes alcohol use less reinforcing. Naltrexone exists in both oral and long-acting injectable (monthly) forms. Naltrexone should be prescribed at the time that psychosocial treatment is initiated. There is a side effect of rare liver toxicity with the use of naltrexone, although it is generally safe and well tolerated (Volpicelli, Alterman, Hayashida, & O’Brien, 1992).

Acamprosate Acamprosate is the latest drug to be approved by the FDA for the treatment of alcohol dependence. Its mechanism of action is not clearly known, but it is assumed to be due the drug’s effect on increasing gamma–aminobutyric acid (GABA) neurotransmission and subsequent changes in the excitatory glutamate neurotransmitter system. Like naltrexone, it is reported to reduce the rate at which alcohol-dependent patients return to drinking (relapse) and is associated with less quantity and frequency of drinking in those who relapsed (Kranzler & Gage, 2008). Unlike disulfiram and naltrexone, acamprosate is not metabolized by the liver and is excreted unchanged by the kidneys. Therefore, kidney function is an important consideration in its use. Side effects commonly include gastrointestinal upset (e.g., diarrhea, bloating) and itching (Boothby & Doering, 2005).

Medications Used in Opiate Dependence There also exist a number of drugs approved by the FDA for the treatment of opiate addiction. These include the opioid agonists buprenorphine, methadone and levo-alpha-acetylmethadol (LAAM) and the opioid mu-antagonist naltrexone. LAAM, although indicated for the treatment of opioid dependence, is no longer marketed because of reports of an association with cardiac rhythm abnormalities. Methadone is available for opiate addiction in the United States only through specially licensed treatment programs, while naltrexone and

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buprenorphine may be dispensed in an office-based primary care or psychiatric setting.

Naltrexone Because naltrexone achieves complete blockade of opioid receptors at therapeutic doses, it greatly reduces the reinforcing properties of opiates (Kosten & Kleber, 1984). While this makes naltrexone a theoretically attractive option to manage opioid dependence, the clinical reality is not so optimistic, with treatment retention rates of only 20 to 30% over 6 months (Kosten, 1990). Several explanations have been put forth for this phenomenon. Unlike opioid agonists like methadone and buprenorphine, naltrexone does not address craving, because it does not have any intrinsic opioid stimulating properties. In addition, if antagonist treatments like naltrexone are stopped, there is no immediate reminder in the form of withdrawal to reinforce adherence. Naltrexone has been found to be very effective for specific groups of patients (such as health care professionals who are in danger of losing a license to practice, or individuals on probation) for whom there is an external incentive to comply with therapy and remain opioid-abstinent, and for otherwise highly motivated patients (Washton, Gold, & Pottash, 1984). Issues of compliance can also be addressed, in part, by the use the long-term injectable formulation.

Buprenorphine Buprenorphine is a partial mu receptor agonist used for the treatment of opioid dependence. A partial receptor agonist is a substance which binds to a specific receptor (the mu opioid receptor in this instance) and then partially stimulates the receptor to a less than maximal response (when compared to a full agonist). Such agonists may even act as receptor antagonists when present in a certain concentration (dose). In 2002, when buprenorphine was approved for the management of opioid dependence, it was an important milestone because it expanded access to opioid dependence treatment. Buprenorphine can be safely administered in office-based practices (Amass et al., 2004). Buprenorphine, although considerably more expensive than methadone, is safer, less liable to abuse, engenders less social stigma, and has a greater degree of acceptability by the general public (Helmus, Downey, Arfken, Henderson, & Schuster, 2001). Methadone use is also complicated by several clinically important adverse reactions in HIV/AIDS patients taking highly active

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antiretroviral therapy (HAART). Buprenorphine presents an attractive clinical alternative in the management of such patients (McCance-Katz et al., 2006).

Methadone Methadone maintenance treatment (MMT) is the most widely available pharmacotherapy for opioid addiction. It has been used for more than 40 years with good efficacy and safety. Long-term methadone maintenance works by relieving the protracted opioid withdrawal syndrome. It also blocks opioid(particularly heroin-) induced euphoria (Dole, 1972; Kosten, 1990). An equally important effect is that it allows for psychosocial stabilization of the patient in the long term. Decreased drug-seeking behavior, good treatment retention, improvement in psychosocial adjustment and relationships, fewer risktaking behaviors (both sexual and injecting behaviors, such as needle sharing) and reduced criminal activity are among the benefits reported (Dole, 1972; Cooper, Altman, Brown, & Chechowicz, 1983; Camacho, Bartholomew, Joe, Cloud, & Simpson, 1996). According to a recent Cochrane review, adding psychosocial interventions to methadone maintenance improves the chance of abstinence from opioids at follow-up (Amato, Minozzi, Davoli, Vecchi, Ferri, & Mayet, 2008).

Regulatory Challenges in Opioid Maintenance Treatment Methadone maintenance and withdrawal treatment are governed by regulations written by the FDA in consultation with the National Institute on Drug Abuse (NIDA) and the U.S. Drug Enforcement Administration. In addition, states typically have their own regulations, most of which are based on federal regulations but may be more restrictive in their provisions. These regulations, unfortunately, have not been able to ensure the quality of patient care. While MMT has some of the most robust evidence for effective management of opioid dependence, these regulations sometimes hinder access. In addition to the restrictive nature of being labeled a prescription narcotic, methadone has a unique third tier of special standards established by the Department of Health and Human Services regulating how and under what circumstances it may be used to treat opioid addiction. Since 2001, these standards have been administered by SAMHSA (the Substance Abuse and Mental Health Services Administration). The purpose of this multilayered regulatory structure is to create a “closed system” of distribution, restricted to hospitals and pharmacies specially designated and controlled to provide methadone. Additionally,

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most states have some type of regulation regarding methadone—sometimes more stringent than the federal regulations. Additional layers of regulation at the county or municipal level also affect how methadone is used. (Rettig & Yarmolinsky, 1995; Dole, 1995; Kissin, McLeod, Sonnefeld, & Stanton, 2006). This regulation has limited patient use of MMT. According to an Institute of Medicine report, only 18 to 36% of heroin users were enrolled in methadone treatment in 1995 (Institute of Medicine, 1995). According to the American Association for the Treatment of Opioid Dependence, in 2004, there were 1,106 opioid treatment programs nationwide, with 54% of these in seven states; six states (Idaho, Mississippi, Montana, North Dakota, South Dakota, and Wyoming) do not have any opioid agonist therapy available. In this context, office-based buprenorphine maintenance is much more accessible and should be more widely available. Despite new federal regulations in 2001 and the availability of buprenorphine for office-based opioid therapy, there has been little growth in this practice. The need for special certification and a lack of a provider base may contribute to this shortage. Currently, no medication is approved by the FDA for the treatment of any other substance dependence, except nicotine dependence. Several classes of medications have been studied for cocaine dependence, none consistently meeting the currently accepted standards for efficacy and safety. Selective serotonin reuptake inhibitors, in several controlled trials, have not been found to be more effective than placebo (Lima, Farrell, Reisser, & Soares, 2003; Winhusen et al., 2005). Disulfiram holds some promise for patients with cocaine (Farren, Scimeca, Wu, & O’Malley, 2008) and concurrent cocaine and alcohol dependence (Suh, Petinatti, Kampman, & O’Brien, 2007).

EVIDENCE FOR COMBINED TREATMENT WITH CBT AND MEDICATION FOR SUBSTANCE USE DISORDERS It is generally accepted that multimodal treatment is the most effective method of managing severe drug and alcohol addiction. The need for psychosocial rehabilitation, family support and intervention, and medical intervention makes combined treatment the rule rather than the exception in such patients. With the advent of medications available to attenuate craving and provide positive reinforcement away from alcohol and other drugs, combining treatments in a more routine way may increase success.

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Combined Treatment for Alcohol Dependence A widely acknowledged premise in all reviews of combined or single treatments for alcohol dependence is that many individuals do not respond to a single modality and that long-term results vary, but leave much to be desired. There is a substantial lack of response to either treatment alone, and the rate of relapse is high—up to 70% of patients resume drinking within a year (Swift, 1999). Combining medication with psychosocial treatment (cognitive and behavioral interventions, or these interventions plus 12-step groups) has been shown to increase the effectiveness of treatment. A review of 24 randomized controlled trials found that acamprosate supports abstinence after alcohol has been discontinued and increases the amount of time to relapse, with a number of nine needed to treat to obtain a significant benefit (Rosner, Hackl-Herrwerth, Leucht, Lehert, Vecchi, & Soyka, 2010). This review also cited three studies that compared naltrexone and acamprosate, with no clear advantage found for either drug with respect to abstinence, a return to heavy drinking, or duration of abstinence. A large clinical trial of combined cognitive behavioral interventions (the COMBINE study) compared acamprosate, naltrexone, cognitive-behavioral interventions (CBI), and medical management in nine treatment groups. The results indicated that after 16 weeks of active treatment, adding naltrexone, CBI, or both to medical management was superior to medical management alone, but the combination of naltrexone and CBI was not superior to either treatment alone (Zarkin et al., 2008). A closer look at combining treatment in a different study measuring CBT and naltrexone indicated the combination was superior to supportive therapy and naltrexone or CBT plus placebo (Balldin et al., 2003). Two specific benefits of CBT and naltrexone occurred in this study: Individuals who received the combination had a decrease in relapse rate to heavier drinking and a greater length of abstinence before drinking. Another effect noted was that those individuals who used alcohol and many other substances did not respond as well, and that more drinking-related parameters change with the combination of CBT and naltrexone than any other combination. A conclusion reached by all the combined treatment studies is that the length of treatment in clinical trials is insufficient to really measure differences in such a chronic illness. A critical issue in planning treatment of alcohol dependent patients is that treatment is not “one size fits all.” Despite multiple studies to determine which

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treatments will work better for which patients, we do not know who will respond to which treatment (Mattson & Litten, 2005). A rational approach to combined treatment for the present would be to tailor interventions that target patient-specific symptoms. For example, a patient with severe craving would more likely benefit from the addition of acamprosate to a naltrexoneCBT intervention; he would also be more likely to need specific efforts in CBT to target symptoms with techniques to manage cravings (“urge surfing”) and cognitive modification regarding predictions about cravings. Patients who require more psychosocial rehabilitation (e.g., who need a sober network of friends) could be directed to increase their exposure to 12-step programs. Another question to consider about combined treatment for substance dependence is the idea of “treatment” versus “cure.” Both therapy and medication may need to be continued in some long-term form in alcohol dependence, given the very chronic nature of the disorder (Miller, Locastro, Longabaugh, O’Malley, & Zweben, 2005). Finally, specific benefits may exist with combined treatment with respect to outcomes besides abstinence (Cisler, Kivlahan, Donovan, & Mattson, 2005). For example, patients who are in combined treatment are more likely to take medication more accurately and more frequently, and have better psychosocial function—this could mean that they have fewer consequences of relapse. Since a central tenet of CBT is skill development and deployment by the patient, teaching patients coping skills regarding alcohol use could mean that future drinking episodes are attenuated. A feature of the cognitive-behavioral intervention provided in the COMBINE study that is very important to consider translating to clinical practice is that the intervention was formulation-driven. Therapy provided motivational enhancement, cognitive-behavioral interventions, 12-step programs, and work with significant others in a tailored fashion, depending on the results of a functional analysis of the patient’s drinking (Longabaugh, Zweben, Locastro, & Miller, 2005). The therapist and patient analyzed the patient’s strengths and skill deficiencies to determine a treatment plan. Such a formulationdriven approach translates a key feature of clinical practice to the research setting and may hold more promise in the treatment of such a refractory illness. One important new study of alcohol dependence indicates that although the combination of sertraline and naltrexone, when there is no evidence of depression, does not increase treatment efficacy (Farren, Scimeca, Wu, &

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O’Mally, 2008), when co-occurring depression and alcohol dependence occur combining treatment improves both abstinence and depression (Pettinati et al., 2010). Previous clinical lore would advise that it is impossible to accurately prescribe antidepressants before sobriety is attained, so that frequently antidepressant medication is withheld early in treatment. It may improve both alcohol use and mood disturbances to use SSRI antidepressants as the initial medication regimen when symptoms of both disorders are present. An example of the clinical management of alcohol dependence is Eric. Eric, a 22-year-old college junior, has used alcohol “recreationally” since the age of 14. He is referred to Dr. Green, a psychologist, from the student health service at his school after his third emergency room visit for severe alcohol intoxication. Eric is at a small college where he does not need to drive, so he has avoided any DUI citations and the risk of a motor vehicle accident. He does not consider abstinence from drinking a possibility while he is in college and is ambivalent about stopping drinking under any circumstances. He does believe cutting down his use might be a good idea because he had three uncles die of alcohol-related complications. He uses no other drugs. Eric is also in some jeopardy academically, because his alcohol use interferes with his studying. He has tried to cut down his drinking, but he finds his thoughts about using and wanting to use increase significantly, and he misses the “relaxed, fun time” he has when he is drinking. Dr. Green carefully assesses Eric’s alcohol use. After a series of educational sessions about the physical and psychological effects of drinking so frequently, she asks Eric if he is willing to set a goal to have a certain number of drinks per week. Eric agrees to a drinking goal of drinking five drinks three nights per week. After three weeks, he is unsuccessful—his friends on the lacrosse team have had parties every night, his housemates continue to drink before going out to “save money” and he joins them, and he has had midterms and drinks afterwards because he “deserves a break.” Eric and Dr. Green discuss Eric’s goals again and how difficult his environment makes it for him to sustain a commitment to staying sober. They approach the environment as a problem. Eric identifies two friends he has who do not drink and agrees to spend one night per week with each of them. Dr. Green also recommends that Eric consider medication. He agrees to see a psychiatrist and to obtain naltrexone to see if combined treatment will help. Finally, Eric works with Dr. Green to identify other potential sources of

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pleasure to enjoy after periods of hard work. Eric labels the thought “I deserve a break” as a trap that gives him permission to drink more. This patient example illustrates two key principles in treating patients with alcohol dependence—establishing a drinking goal and augmenting tailored psychosocial interventions with medications to increase the likelihood of abstinence.

Combined Treatment for Drug Dependence There is substantial evidence that CBT is effective for drug abuse and dependence as a single modality of treatment. The magnitude of the effect varies depending on the substance. A meta-analytic review of 34 studies of CBT used for various substances showed a moderate effect with cannabis, followed by cocaine and opiates in decreasing order. The lowest effect size was found in polysubstance use (McHugh, Hearon, & Otto, 2010). A significant component of CBT for drug abuse is contingency management. When patients are given tangible rewards for abstinence from drugs (e.g., food, money, vouchers), they are far more likely to remain substance-free. Unfortunately, most treatment programs have limited funding for such approaches, and culturally these programs are a hard “sell.” Our culture tends to blame drug users as “bad” and undeserving of rewards for abstaining—instead, resources are focused on punishment for use. Contingency management is most effective when it provides tangible rewards in exchange for negative drug tests (Carroll & Onken, 2005). Such a reward system stops working when the rewards stop and is frequently limited by cost. One of the significant problems encountered in treating severe substance abuse in urban settings is that patients are frequently living in a subculture that revolves around illicit drug use— stimulus control is often extremely difficult to accomplish, and the patient’s sense of self-efficacy is often rooted in skills involved with drug and alcohol use. Significant efforts to “wrap around” services that provide a new environment for the patient in combined treatment are key to success. In clinical settings, this finding should also translate into active work with patients to build in reinforcing activities for abstinence. Family members can also facilitate this process by engaging in rewarding activities with the patient when he does not use. Evidence from a number of studies reviewed regarding combinations of CBT for drug abuse and medication treatments supports the addition of contingency management to methadone maintenance and the addition of either

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disulfiram (Farren et al., 2008) or citalopram to CBT in cocaine dependence (McHugh et al., 2010). The addition of disulfiram was particularly effective for nondrinkers who abused cocaine, suggesting some particular direct effect of disulfiram in cocaine abusers. Finally, significant results have been obtained with adjunctive computerassisted CBT in substance abuse—with longer abstinence from multiple types of substances and a reduced frequency of positive urine tests (Carroll et al., 2008). Patients who practiced computer-assisted CBT biweekly completed more homework assignments, in addition to the positive benefits to reduce drug use. Such a delivery system may make CBT more widely available to substance abuse treatment program participants.

SPECIAL CONSIDERATIONS IN COMBINED TREATMENT FOR SUBSTANCE ABUSE AND DEPENDENCE Severe and Persistent Mental Illness (SPMI) and Substance Misuse As reviewed in multiple chapters in this volume, substance use combined with chronic psychiatric illness has a substantially negative effect on the outcome of both disorders. Small amounts of substances can accelerate or exacerbate symptoms of schizophrenia, bipolar disorder, and anxiety disorders. Substance abuse can increase impulsivity and impede judgment. Suicidal behavior increases. Patients often have significant medical and psychosocial consequences, including hepatitis C, HIV infection, and loss of stable housing and relationships. Incarceration is more likely. Victimization—financial, physical, and sexual—occurs at a higher rate. Patients with SPMI who misuse substances are more likely to miss medication doses and relapse. Unfortunately, the prevalence of both disorders is fairly high; with some studies reporting more than 50% of patients in urban areas being dually diagnosed (Cleary, Hunt, Matheson, Siegfried, & Walter, 2010). Despite the severity of this problem, and the substantial psychological, social, and medical costs, the information that we have to guide our treatment approach is minimal. A recent systematic review (Cleary et al., 2010) found only 25 randomized controlled trials, which are very difficult to compare because they involve different disorders, different measures, and sampling. No clear advantage for any particular approach was noted. Most experts agree that

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integrating approaches to both disorders is the most effective approach to care for such patients (Daley & Marlatt, 2006). Clinicians treating both disorders must be attentive to the level of care appropriate to the patient’s needs and integrate recovery approaches as much as possible. Whenever possible, support groups that match the patient with other individuals suffering similar concerns (e.g., for dual-diagnosis patients) will be the most engaging place for the patient to acquire information and skills. Patients with co-morbid substance abuse and severe and persistent mental illness need as many ancillary supports as possible to promote recovery. These may include family interventions, housing, medical care, spiritual recovery, and leisure time activities. Homeless patients with dual diagnoses are particularly prone to victimization and trauma and should be assessed for PTSD. In addition, they frequently have unresolved medical disorders that contribute to excess morbidity and mortality if left unchecked. Betty, a patient we met in Chapter 9, is a good example of the challenges faced in such patients. Betty is 35 years old and has a 16-year history of schizophrenia. She began to use alcohol and marijuana at age 12, and by age 15 she was an active crack cocaine user. She has not had a permanent residence for ten years. Her boyfriend, Jack, an active crack cocaine user, provides her with drugs whenever she is in contact with him; he also exploits her financially and sexually. After a successful stay in transitional housing, Betty was discharged to outpatient follow-up in a psychiatric clinic and a 12-step program, and went to live with her sister, who supported Betty’s sobriety. Jack persisted in contacting her, however, and Betty had a relapse on cocaine that resulted in rehospitalization for disorganized behavior (she was found wandering in traffic). Betty, her sister, and her therapist met to problem-solve the continual pattern of returning to Jack and relapsing. Betty agreed to block calls from Jack’s number to her cell phone. She was particularly upset about having blown a “second chance” at her sister’s and was grateful for her sister’s reassurance that she could return. Betty was enrolled in a day program to increase her daytime structure.

Pregnancy Abuse of substances by a pregnant woman means, by definition, a highrisk pregnancy. There is the potential for serious consequences for the health of both the mother and fetus in this circumstance (Keegan, Parva,

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Finnegan, Gerson, & Belden, 2010). In the United States, substance abuse during pregnancy has increased significantly over the past three decades. This increase results in 225,000 infants each year with prenatal exposure to illicit substances (Kuczkowski, 2007). When a pregnant woman reveals a history of substance abuse, every effort should be made to refer her to a treatment program, preferably one that is closely associated with prenatal care resources. The substance-abusing pregnant woman should be given particular attention when evaluated in prenatal visits and during the management of labor and delivery. Maintaining a nonthreatening, nonjudgmental, and empathic stance with the patient is vital to motivating the patient. Engagement may be particularly challenging and frustrating if the addicted patient presents with bizarre, erratic, angry, or uncaring behavior (Byrne & Learner, 1992). In many instances, pregnancy may act as a sentinel event that helps substance-using mothers begin to come to terms with the highly self-destructive nature of the abuse and/or dependence. Such insight can also have an unanticipated positive impact on their unborn or newborn children (Keegan et al., 2010). Multiple substances used during pregnancy risk harm to the fetus. Nicotine is a common substance used during pregnancy, and has a strong association with spontaneous miscarriage, fetal growth retardation, and preterm birth. Pregnant women who use heroin experience a sixfold increase in maternal obstetric complications, including fetal growth retardation, third-trimester vaginal bleeding, malpresentations, preterm birth, and other complications after birth (Minozzi, Amato, Vecchi, & Davoli, 2008). Up to 95% of infants exposed to heroin in utero experience a withdrawal syndrome, which can be quite severe and require neonatal specialty care (Andre, 2004). Methadone maintenance for an opioid dependent woman during pregnancy has been demonstrated to result in decreased use of illicit substances, better compliance with prenatal care, and improved newborn birth-weight (Minozzi et al., 2008). The use of combined treatment in this population may have a substantial salutary effect on the outcome for mother and baby alike. Cocaine abuse during pregnancy is associated with fetal growth restriction, catastrophic placental abruption, and stillbirth. Amphetamine use, like cocaine, is associated with poor maternal nutrition and subsequent growth retardation in the fetus. Women using either of these substances when pregnant need early and aggressive intervention to help them abstain as much as possible to avoid significant negative outcomes for the infant.

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Prescription drug abuse must also be considered when evaluating pregnant women. Significant consequences exist for the fetus following prenatal exposure to many prescribed medications that are commonly used or abused. Benzodiazepine abuse during pregnancy during the first trimester may result in congenital abnormalities and is associated with fetal sedation and withdrawal at the time of delivery. Such a neonatal syndrome complicates the newborn’s adaptation to extrauterine life (Keegan et al., 2010). Long-term effects on the fetus of in utero benzodiazepine exposure are not known. Additionally, sedativehypnotics (including benzodiazepines) are readily excreted in breast milk and are not considered safe for lactation.

HIV/AIDS and Hepatitis Infections Blood-borne and sexually transmitted infections are common complications of alcohol and other drug use (Cherubin & Sapira, 1993; Brown & Levine, 2002). In the United States, in adults with known risk factors for HIV infection, diagnosed with the disease between 2001 and 2005, 33% reported injection drug use and another 17% reported sexual contact with an injection drug user (Centers for Disease Control, 2007). Patients must be assessed for these and other infectious diseases (e.g., other sexually transmitted diseases, tuberculosis) at initial referral. HIV/AIDS patients who are substance-dependent adjust to their illness less well than other patients with the disease because of their reliance on drug use and other forms of avoidance to cope with distress. This causes a vicious circle, since maladaptive coping is associated with poor adjustment to HIV disease and increased psychological distress (Avants, Warburton, & Margolin, 2001). Although substance abusers have a greater level of psychological distress compared to their nonabusing peers when undergoing HIV testing, informing them about a positive test result does not result in a worse outcome in their drug-abuse treatment (Perry, Jacobsberg, Card, Ashman, Frances, & Fishman, 1993; Wimbush, Amicarelli, & Stein, 1996). Additionally, the process of undergoing testing for HIV and having a positive result disclosed does not appear to increase the risk of suicide (Van Haastrecht, Mientjes, van den Hoek, & Coutinho, 1994), and recommending testing is an important public health measure. Drug-abuse treatment itself reduces the risk of HIV infection in at-risk populations (Sorensen & Copeland, 2000). The evidence for this is strongest for methadone maintenance treatment, but other treatment modalities also reduce HIV risk (Hubbard, Craddock, Flynn, Anderson, & Etheridge, 1997).

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An example is the Community Reinforcement Approach (CRA), a manualized behavioral treatment approach, which has demonstrated improvement in injection risk behaviors among methadone-maintenance patients with HIV/AIDS (Abbott, Moore, Weller, & Delaney, 1998). The Matrix model, which also utilizes behavioral principles in an intensive outpatient setting, is another approach with demonstrated efficacy in treating cocaine and methamphetamine addiction and reducing HIV risk behaviors (Rawson et al., 1995; Shoptaw, Rawson, McCann, & Obert, 1994). Thus, combined treatment with HIV medication and CBT or with MMT-HIV medication and CBT in this vulnerable group may have substantial public health implications. Hepatitis B and C are other significant infections associated with substance use. Injection drug use is the commonest associated risk factor for hepatitis B infection acquired in adults (Lamagni et al., 1999). While injection drug use is a well-established risk factor for hepatitis B and C, it has also been found that Hepatitis C is more common among alcoholics than the general population (Rosman, Paronetto, Galvin, Williams, & Lieber, 1993; Sata et al., 1996). Current recommendations for the treatment of chronic hepatitis C advise against treating patients with available agents (like interferon) when there is an active ongoing addiction until the substance abuse has stabilized (National Institutes of Health, 1997). However, there is also good evidence that patients maintained in stable methadone and buprenorphine treatment can be successfully managed with hepatitis C treatment (Davis & Rodrigue, 2001; Edlin et al., 2001). If opioid-addicted patients seek hepatitis C treatment, methadone maintenance therapy should be encouraged whenever possible, since the combination may benefit both illnesses (Novick, 2000). Although working with patients with substance abuse and dependence is challenging, the combination of CBT and medications may produce a better outcome than either treatment alone in a costly and chronic illness. Stigma and countertransference contribute to a lack of access to evidence-based treatment for many. Advocacy and effective care are our best hope for better outcomes in such difficult patients.

Combining CBT and Medication: An Evidence-Based Approach by Donna M. Sudak Copyright © 2011 John Wiley & Sons, Inc.

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Combining CBT and Medication: An Evidence-Based Approach by Donna M. Sudak Copyright © 2011 John Wiley & Sons, Inc.

Author Index Abbott, P. J., 208 Abbott, R., 59, 227 Aborzian, S., 212 Abramowitz, J. S., 116 Abramson, L., 209 Addis, M. E., 215 Addolorato, G., 220 Adridge, A., 235 Aghanjanian, J., 182 Agras, W. S., 124, 125, 126 Aikens, J. E., 36, 44 Ait-Daoud, N., 220 Akkermans, R., 77 Alazraki, A., 211 Alda, M., 81 Allen, H., 230 Allen, M. H., 229 Allmon, D., 73 Alloy, L., 61, 74 Alpert, J. E., 216, 226 Alterman, A. I., 196 Altman, F., 198 Altshuler, L. L., 96, 182, 214 Alvanzo, A., 224 Alvarez, J., 61 Amass, L., 197 Amato, L., 198, 206 Amicatelli, A., 207 Amsterdam, J. D., 64, 159, 216, 219, 222, 232 Andersen, A. E., 127 Anderson, J., 207 Andersson, G., 57 Andre, R. L., 206 Angst, J., 99 Annon, J. J., 209 Anton, R. F., 220 Applewhaite, G., 37, 141 Araga, M., 224 Arango, C., 153 Arensman, E., 223 Arfken, C. L., 197 Armstrong, H. E., 73 Arnow, B., 220

Ascher-Svanum, H., 141 Ashman, T., 207 Atkins, D. C., 215 Au, S. C., 212 Avants, S. K., 207 Ayers, R., 218 Babcock, D., 209 Babuscio, T. A., 213 Bacaltchuk, J., 124, 136 Baekeland, F., 195 Baker, J., 224 Bakker, A., 114, 233 Balasubramani, G. K., 216, 232, 234 Baldessarini, R. J., 60, 82, 86, 87, 96, 112, 183 Ball, S. A., 213 Balldin, J., 200 Balon, R., viii, 19, 20 Barber, A. M., 121 Barlow, D. H., 3, 112, 113 Barnes, T. R. E., 230 Barocka, A., 227 Barraclough, B., 153 Barrett, C. L., 5 Barrowclough, C., 155 Bartholomew, N. G., 198 Basco, M. R., 87, 147, 235 Basden, S., 227 Basoglu, M., 113, 223 Bassel-Duby, R., 222 Baxter, J. P., Jr., 14 Baxter, L., 212 Baxter, L. R., Jr., 14, 212 Beaudoin, G., 227 Beauregard, M., 227 Beck, A. T., x, 87, 212 Beck, J. S., 39, 44, 51 Belden, M., 206 Bellino, S., 160 Belluardo, P., 60, 216 Bendsen, P., 210 Benmansour, S., 17

235

Berger, P., 235 Berglund, M., 210 Bergman, K. S., 211 Berman, S. R., 14 Bernstein, C., 96, 182 Beumont, P., 225 Beyers, K., 220 Bieling, P., 217, 221 Biggs, M. M., 216, 232 Bille-Brhae, U., 223 Birchwood, M., 141 Birmaher, B., 231 Birmingham, C. L., 225 Birnbaum, S., 222 Bissada, H., 121 Bizzell, J., 215 Bjartveit, M., 156 Blaauw, B. M., 210, 233 Black, D. W., 116 Blanchard, M., 230 Blanco, C., 115 Blizard, R., 234 Bloch, D. A., 235 Bobes, J., 153 Bockting, C. L. H., 5, 59 Bodman, L. M., 235 Bogen, D., 225 Bogen, D. L., 235 Bogetto, F., 160 Bollini, P., 4, 59 Boothby, L. A., 196 Borian, F. E., 232 Bouan, F. E., 226 Bourgouin, P., 227 Bourne, M. L., 220 Bouton, M. E., 112 Bowden, C. L., 229 Bradwejn, J., 121 Bray, J. W., 235 Bregan, A., 225 Brent, D. A., 231 Brethen, P. R., 228 Brewin, C. R., 211 Brigham, G., 209

236

Author Index

Brody, A. L., 14, 15 Brown, B., 198 Brown, G., 72, 73, 79 Brown, L. S., 209 Brown, P. D., 207 Brown, R. A., 225 Brown, S., 153, 156 Bruce, T. J., 113 Buchan, B. J., 209 Buck, J. A., 33 Buis, T., 229 Bulik, C. M., 224 Burbeck, R., 37, 83 Burns, B., 223 Burt, V. K., 96, 182 Burwell, R. A., 219 Bush, T., 220 Buszewicz, M., 230 Bux, D. A., 116 Byrne, M. W., 206 Bystritsky, A., vii, 229 Cahill, S., 230 Calabrase, J. R., 224, 229 Calkin, C., 81 Camacho, L. M., 198 Campeas, R., 211 Canestrari, R., 60, 216 Capece, J. A., 220 Carballo, J. J., 231 Card, C. A., 207 Cardish, R., 221 Carey, T. S, 196 Carmin, C. N., 216 Carney, R. M., 4 Carroll, K. M., 203, 204 Carter, D., 225 Carter, F. A., 224 Carter, N., 224 Chambers, C. D., 187 Chapman, L., 225 Cheavens, J. S., 133 Chen, H., 211 Chen, I. J., 183 Chen, J., 222 Chen, Y. H., 183 Cherubin, C. E., 207 Chiu, A. W., 61 Chiu, W. T., 55 Churchill, R., 114 Ciccarone, D. H., 215 Ciraulo, D. A., 220 Cisler, R. A., 201, 235

Clark, C., 209 Clark, L. A., 59 Clark, R., 184, 190 Cleary, M., 204 Cloud, M. A., 198 Cochran, S. D., 36 Cochrane, R., 141 Coffman, S. J., 64 Cohen, A. J., 209 Cohen, J., 121 Cohen, L. S., 183 Coleman, F. S., 235 Colom, F., 82 Compton, J. S., 214 Connor, K. M., 214 Conti, S., 60, 216 Cook, M., 221 Cooper, J. R., 198 Cooper, P., 225 Cooper, Z., 227, 228 Copeland, A. L., 207 Corcoran, P., 223 Cornes, C., 216 Cornwall, P., 227 Couper, D. J., 235 Coutinho, R. A., 207 Cowen, P. H., 17, 218 Craddock, S. G., 207 Craske, M. G., vii, 229 Creed, F., 184 Crews, F. T., 196 Crits-Christoph, P., 226 Crossfield, A. G., 209 Crow, S. J., 209 Cuijpers, P., 57 Curry, J., 223 Curt, V. K., 214 Czechowicz, D., 198 Dackis, C. A., 228 Dadds, M. R., 218 Daley, D. C., 205 Daversa, M. T., 218 David, A., 37, 141 Davidson, J. R., 115 Davis, C. E., 222 Davis, G. L., 208 Davis, L., 234 Davis, M., 115 Davis, S. M., 222 Davison, K, L., 222 Davoli, M., 198, 206 Deacon, B. J., 221

Deep, D., 220 deKloet, E. R., 228 Delaney, H. D., 208 De Leo, D., 223 Demler, O., 55 Dennehy, E. B., 229 deOliveira, I. R., 125 deRijk, R. H., 228 DeRubeis, R. J., 57, 61, 64, 159, 216, 222, 232 Devlin, M J., 233 Dichter, G. S., 16 Dick, L. M., 187 Diemer, J., 110 Dimidjian, S., 64, 67, 216 Dobson, K. S., 215 Dobson, S., 215 Doering, P. L., 196 Dolder, C. R., 141 Dole, V. P., 198, 199 Domino, M., 223 Donohue, G., 226 Donovan, D., 201 Dorer, D. J., 215, 219 Dowd, S. M., 19 Downey, K. K., 197 Dozois, D. J. A., 16 Drevets, W. C., 11 Drury, V., 141 Dubo, E. D., 235 Duivenvoorden, H., 161 Dundon, W. D., 228 Dunn, T. W., 59 Dunner, D. L., 215, 220, 225, 232 Dyck, I., 218 Eaves, L., 228 Eckert, E., 121 Eddy, K. T., 123 Edlin, B. R., 208 Eisenmenger, K., 227 Ekeblad, E. R., 219 Elkashef, A., 235 Ernst, M., 215 Erwin, B. A., 211 Etheridge, R. M., 207 Etkin, A., 13 Evans, J., 183 Evans, M. D., 61 Everitt, B., 37, 142, 220 Faedda, G. L., 183 Fairbank, J., 223

Author Index Fairbanks, L. A., 212 Fairbrother, N., 224 Fairburn, C. G., 119, 125 Faries, D., 141 Farmer, M. E., 228 Farrell, M., 199 Farren, C. K., 199, 201, 204 Fasiczka, A. L., 14 Fassbender, J., 42 Fava, G. A., 60, 79 Fava, M., 55, 78, 217, 226, 232, 234 Favaron, E., 218 Fawcett, J., 216 Feeley, M., 61 Feeny, N. C., 116 Fekete, S., 223 Felder, J. N., 215 Felix, R. J., 187 Ferng, H. K., 211 Ferri, M. M., 198 Finnegan, M., 206 Finos, L., 216 Fiori-Cowley, A., 225 Fischer, H., 217 Fishman, B., 207 Fitzmaurice, G., 133 Fleiss, J., 233 Flores, A. T., 219 Flynn, P. M., 207 Foa, E. B., 214, 230 Fossey, M. D., 229 Fournier, J. C., 57, 62, 64, 159 Fowler, D., 143 Frampton, C. M. A., 224 Frances, A., 207 Franch, J., 210 Francomb, H., 183 Frank, E., 58, 224 Frankenberg, F. R., 235 Frankenburg, M. D., 133 Franklin, M. E., 116, 214 Franko, D. L., 215 Frazer, A., 17 Frederikson, M., 217 Freeman, B. B., 219 Freeman, R., 123, 127 Freese, T. E., 209 Fresco, D. M., 211 Frewen, P. A., 16 Friedman, E. S., 57, 229, 232 Friendland, G., 224 Fukuizumi, K., 229

Furmark, T., 14 Furukaura, T. A., 114 Gabbard, G., 19, 178 Gadde, K. A., 214 Gafalvy, H. C., 231 Gage, A., 196 Galletly, C. A., 180 Gallis, T. L., 228 Gallop, R., 64, 215, 216, 219, 222 Galvin, K., 208 Garband, A., 227 Garbutt, J. C., 196 Garcia-Garcia, M., 153 Gardner, H. A., 226 Garner, B., 117 Garner, D. M., 124, 125 Garson, C., 217 Gaston, J. E., 218 Gaynes, B. N., 7, 234 Gelenberg, A. J., 220 Gemar, M., 229 Gerner, R. H., 93 Gerson, A., 206 Ghiani, C., 60, 86, 112, 183 Gibb, B., 209 Gijsman, H., 99 Gill, O. N., 222 Gillies, L. A., 212 Gledhill, A., 232 Glover, V., 183 Goekoop, J. G., 228 Gold, M. S., 197 Goldapple, K., 15 Golding, J., 183 Goldman, L. S., 153, 156 Goldsmith, J. R., 235 Golinelli, D., 229 Gollan, J. K., 215 Gonzalez, J. M., 224 Gooding, P., 73 Goodwin, F. K., 93, 228 Goodwin, G. M., 17, 218 Gordon, A., 225 Gordon, M. A., 213 Gorman, J. M., 3, 4, 113 Gotlib, I. H., 18 Gould, R. A., 124 Graczyk, P. A., 182 Grandi, S., 60, 216 Gray, J., 234 Greenwood, D. N., 219

237

Griem, A., 228 Griest, J. H., 115 Grilo, C. M., 218, 233 Groat, R., 124 Grochocinski, V. J., 216 Grol, R., 77 Grothaus, L., 230 Gruman, R. E., 225 Guastella, A. J., 115 Gunderson, J. G., 162, 163, 233 Gupta, S., 133 Gurmu, Samson, ix Gustafsson, L., 210 Guze, B. H., 211 Gyulai, L., 87, 224, 227, 229 Hackl-Herrwerth, A., 200 Haddock, G., 211, 232 Haggard, P., 220 Hajek, T., 81 Halldin, J., 210 Hallmayer, J., 18 Halmi, K. A., 120, 121, 130, 209 Haman, K. L., 219 Hanusa, B. H., 108, 235 Harlow, B. L., 214 Harman, J. S., 108 Harner, C. J., 17, 62 Harrer, J. M., 235 Harries, R., 226 Harwood, H., 194 Hasson, A. L., 228 Hauser, P., 229 Have, T. T., 212 Hawkins, M., 220 Haworth, D., 230 Hawton, K., 223 Hay, B. P., 124 Hay, D. F., 230 Hay, P. J., 136 Hayashida, M., 196 Hayhurst, H., 227, 228 Hayward, P., 37, 141, 234 Heard, H. L., 73 Hearon, B. A., 203 Heiligenstein, J., 230 Heim, C. M., 225 Heimberg, R. G., 211 Helmus, T. C., 197 Hembree, E., 230 Henderson, M. J., 197 Hendrick, V., 214 Hennen, J., 87, 96

238

Author Index

Hennessey, G., 97 Henriques, G. R., 212 Hernandez-Diaz, S., 213 Heron, J., 183 Herrell, R., 228 Hertzman, C., 182 Herzog, D. B., 123, 215 Hetrick, S. E., 117 Higgitt, A., 234 Hjelmeland, H., 223 Ho, M., 212 Ho, M. K., 212 Hodgekins, J., 143 Hoffman, S. G., 227 Hoh, J., 228 Hollander, J. E., 212 Hollon, S. D., 57, 59, 61, 64, 159, 215, 216, 222, 232, 234 Hood, K., 229 Hooper, R., 225 Hope, V. D., 222 Horton, T., 209 Houck, P. R., 79 Howland, A., 216 Howland, R. H., 232, 234 Hsia, J. K., 222 Hsu, L. K., 120, 220 Huang, S. C., 212 Hubbard, R. L., 207 Hucker, S., 155 Hudson, J. I., 125 Huedo-Medina, T. B., 221 Humphreys, L., 232 Hunker, D. F., 235 Hunt, G. E., 204 Huppert, J. D., 214, 230 Huxley, N., 87 Ingenhoven, T., 161 Innis, R. B., 11 Inskip, H., 153 Ishii, K., 229 Jabs, B., 110 Jackson, W., 162, 169 Jacobsberg, L., 207 Jacobson, N. S., 215 Jamison, K. R., 93 Janicak, P. G., 19 Jarret, D. B., 216 Jarrett, R. B., 57, 59 Jatlow, P., 224 Jefferson, J. W., 115

Jenarvay, A., 227 Joe, G. W., 198 Joffe, R., 14 John, L. K., 42 John Mann, J., 231 Johnson, A. L., 227 Johnson, B. A., 194 Johnson, B. T., 221 Johnson, K. A., 187 Jones, K. L., 187, 213 Jones, P., 156 Jones-Ivy, S., 235 Joormann, J., 18 Jordan, J., 224 Joyce, P. R., 224 Judd, L. L., 228 Juster, H. R., 211 Kampman, K., 199, 228 Kandel, E. R., 10 Katon, W. J., 65, 229, 230 Katzelnick, D. J., 115 Kaye, J., 19, 178 Kaye, W., 120, 123 Keck, P. E., 82 Keefe, B. R., 226 Keefe, F. J., 214 Keefe, R. S., 222 Keegan, J., 205, 206, 207 Keel, P., 219 Keeley, H. S., 223 Keith, S. J., 228 Keitner, G. I., 5, 62, 87, 225 Kelleher, M., 223 Keller, M. B., 3, 57, 58, 78, 87, 219, 225, 226, 232 Kemp, R., 37, 141 Kendrick, K., 225 Kennedy, N., 59, 229 Kennedy, S., 217 Kennedy, S. H., 16 Kerkhof, A. J., 223 Kernie, S. G., 222 Kerr, J., 227 Kessler, R. C., 55, 107 Ketter, T. A., 227, 229 Kilic, C., 211 King, M., 230 Kingdon, D., 230 Kingdon, D. G., 143, 147 Kinney, C., 232 Kinsella, A., 226 Kirby, M., 223

Kirov, G., 37 Kirsch, I., 62 Kissin, W., 199 Kivlahan, D. R., 201 Kleber, H. D., 197 Klein, D. N., 220, 225, 232 Klerman, G. L., 107 Klinkman, M. S., 36 Knauz, R. D., 228 Knesevich, M. A., 4 Kobak, K. A., 115 Koeter, M. W., 59 Kogan, J. N., 224 Kohen, D., 191 Kohlenberg, R. J., 215 Kolla, N. J., 172 Konarski, J. Z., 221 Koren, G., 226 Kornstein, S. G., 225, 226, 232 Kosten, T. R., 197, 198 Kovacs, M., 228 Kraemer, H. C., 125, 209 Kral, A. H., 215 Kranzler, H. R., 196, 220 Krawitz, R., 162, 169 Krejci, J., 209 Krystal, J. H., 11, 227 Kuan, A. J., 224 Kuch, K., 113 Kuck, K., 223 Kuczkowski, K. M., 206 Kueppenbender, K. D., 218 Kulin, N., 226 Kuman, R., 230 Kumashiro, R., 229 Kupelnick, B., 4, 59 Kupfer, D. J., 216 Kwon, C.-H., 222 Lacro, J. P., 141 LaDu, T. J., 121 Lafay, P., 161 Lam, D., 37 Lam, D. H., 81, 83 Lamagni, T. L., 208 Langstrom, B., 217 Lanius, R. A., 16 Lanka, G. D., 230 Larkin, C., 226 Lau, J. Y., 229 Lau, M., 217, 221 Laurant, M., 77 Leahy, R. L., 87

Author Index Lebowitz, B., 232 Lebowitz, B. D., 222 Lecompte, D., 36, 37, 141 Ledley, D. K., 230 Lee, H. C., 183 Leeuwenkamp, O. R., 140 Lehert, P., 200 Lehner, T., 228 Leiderman, D. B., 235 Lelliot, P. T., 223 Lenze, E. J., 108 Lepri, B., 60, 86, 112, 183 Lerner, H. M., 206 Leroux, J. M., 227 Leslie, V. C., 226 Leucht, S., 200 Leuchter, A., 216 Levesque, J., 227 Levin, A., 235 Levin, B., 225 Levin, F. R., 97 Levine, D. P., 207 Levit, K. R., 33 Lewinsohn, P. M., 69 Lewis, C. P., 113 Lewis, S. W., 211 Leykin, Y., 62 Li, Y., 10 Liang, K. Y., 228 Liberzon, I., 16 Licht, R. W., 99 Lieb, K., 161 Lieber, C. S., 208 Lieberman, J. A., 140 Liebowitz, M. R., 211, 230 Lima, M., 199 Lima, M. S., 125 Lin, E., 220 Lin, H. C., 183 Linardatos, E., 62 Linden, D. E. J., 11, 13, 15 Lindstrom, E., 156 Linehan, M. M, 73, 173 Ling, W., 209, 228 Links, P. S., 221 Litten, R. S., 201 Lo, B., 215 Locastro, J. S., 201 Locke, B. Z., 228 Loeb, K. L., 233 Loewenstein, G., 42 Lohr, K. N., 196 Longabaugh, R., 201

Lonnqvist, J., 223 Lorvick, J., 215 Loughead, A., 214 Louik, C., 213 Lovejoy, M. C., 182 Lovett, M. L., 219 Lovibond, P. F., 218 Ludman, E., 220, 230 Luikart, B., 222 Lundwall, L., 195 Luty, S. E., 224 Luutu, J. W., 222 Lynch, T. R., 133, 214 Macmillan, F., 141 MacPhillamy, D. J., 69 Madonia, M. J., 79 Maidment, K., 212 Malik, A., 184 Mallinger, A. G., 216 Manber, R., 226, 232 Mancini, A. D., 133 Mann, K., 220 Mansson, M., 210 Mao, L., 220 Marangell, L. B., 224, 227, 229 March, J., 3 Marcus, S. C., 64 Margolin, A., 207 Mari, J. J., 124, 125 Marinelli-Casey, P. J., 228 Mark, T. L., 33 Markley, D. K., 215 Markowitz, J. C., 220, 232 Markowitz, J. S., 107 Marks, I., 110, 113, 211 Marlatt, G. A., 205 Marteinsdottir, I., 217 Martell, C. R., 64 Martin, E., 15 Martin, K. M., 14 Martin, S. D., 15 Martinez, J. M., 229 Martino, S., 213 Massey-Chase, R., 218 Matheson, S. L., 204 Matthews, A. M., 62 Mattia, J. I., 5 Mattson, M. E., 201 Mayberg, H., 16, 217 Mayberg, H. S., 221 Mayet, S., 198 Mazziotta, J. C., 211

239

McAuliffe, C., 97 McCance-Katz, E. F., 198 McCann, M. J., 208, 228 McCarthy, E., 232 McCarty, D., 209 McConaha, C., 220 McCullough, J. P., 220 McCullough, J. P., Jr., 225 McEachran, A. B., 216 McElroy, S. L., 220 McEvoy, J. P., 222 McGlashan, T. H., 218, 233 McGlinchey, J. B., 215 McGovern, J., 211 McGrath, P. J., 232 McHugh, K., 203, 204 McIntosh, V. V. W., 130 McIntyre, R., 221 McKay, A., 220 McKenzie, J. M., 224 McKnight, R. F., 121 McLeod, C., 199 McMain, S., 221 McNamee, G., 223 McNulty, S., 223 Meltzer-Brody, S., 227 Mennes, M., 183 Mensour, B., 227 Merikangas, K. R., 228 Meuiner, S. A., 227 Mezinskis, J. P., 235 Michel, K., 224 Mientjes, G. H., 207 Migone, M., 226 Miklowitz, D. J., 83, 84, 227, 229 Miller, I. W., 5, 62, 87 Miller, W. R., 201 Mills, M. J., 235 Mineka, S., 112 Minor, K., 18 Minozzi, S., 198, 206 Misri, S., 182, 187, 188 Mitchell, A. A., 213 Mitchell, J. E., 124, 209 Mitchell, P., 218 Mitra, D., 235 Mizokami, M., 229 Mondraty, N., 121 Montgomery, M. A., 235 Moody, D. E., 224 Moore, B. A., 208 Moore, L. D., 215 Moore, R., 227

240

Author Index

Moore, T. J., 221 Moreno, C., 231 Morey, L. C., 218, 233 Moring, J., 211 Morphy, M. A., 60, 216 Morrell, W., 123, 127 Morris, J., 232 Morrisin K., 110 Morse, G. D., 224 Moses-Kolko, E. L., 187, 235 Mueller, T. I., 194 Muir, J. A., 209 Mulder, E. J., 183 Munford, P., 211 Munizza, C., 4, 59 Murad, S., 230 Murphy, G. E., 4 Murphy, K., vii Murray, L., 190 Nakano, H., 229 Nataga, T., 220 Neal, C., 183 Nease, D. E., 36 Nemeroff, C. B., 57, 220 Neuman, G., 182 Newcomer, J. W., 157 Newham, J. A., 222 Newman, C. F., 87, 98 Newport, D. J., 214 Nich, C., 213 Nierenberg, A. A., 55, 219, 224, 227, 229, 232, 234 Nilsson, L. H., 210 Ninan, P. T., 57, 78, 225, 232 Nolen, W. A., 99 Nonacs, R., 214 Norquist, G., 232 Norshirvani, H., 223 Norton, L., 42 Novick, D. M., 208 Nulman, I., 188 Nuro, K. F., 213 Oberlander, T. F., 182, 187, 224, 225 Obert, J. L., 208, 228 O’Brien, C. P., 196, 199, 228 O’Brien, R., 211 O’Callaghan, E., 226 O’Carroll, M., 230 O’Cleirigh, C. M., 112 O’Donnell, C., 141

O’Donovan, C., 81 Ogundele, A., 224 O’Hare, E., 182 Oke, S., 183 Olfson, M., 64 Olfson, M. D., 183 Olmstead, M. P., 124 O’Malley, S., 199, 201, 202, 220 Onken, L. S., 203 Oquendo, M. A., 231 Oslin, D. W., 228 Ostacher, M. J., 229 Ostacher, M. L., 227 O’Sullivan, G., 223 O’Sullivan, U. O., 17, 62 Ott, J., 228 Otto, M. W., 110, 115, 203, 224, 227, 229, 230, 231 Ovelette, R., 107 Owens, N., 226 Pace-Asciak, P., 226 Pade, P., 224 Pampallona, S., 4, 59 Paquette, V., 14 Parada, L. F., 222 Park, R. J., 121 Paronetto, F., 208 Parry, J. V., 222 Parslow, R., 117 Parva, M., 205 Passchier, J., 161 Patel, J., 229 Patel, J. K., 229 Patterson, T. L., 140 Pava, J. A., 226 Pawlby, S., 230 Paykel, E. S., 8, 58, 59, 60, 228 Pearlson, G. D., 227 Pecknold, J. C., 113 Pedersen, R., 229 Pelc, I., 36, 37 Perel, J., 225 Perel, J. M., 216, 235 Perkins, D. O., 222 Perlis, R. H., 83, 87 Perris, C., 37, 141 Perry, S., 207 Petinatti, H., 199 Petinatti, H. M., 202 Petrycki, S., 223 Petty, C., 215 Phelps, M. E., 14, 211, 212

Pieracci, A. M., 209 Pike, K. M., 233 Pilling, S., 37, 83 Pissiota, A., 217 Plotnicov, K. H., 220 Polivy, J., 124 Pollack, M. H., 227, 230 Pompili, M., 82, 210 Pope, H. G., 125 Pope, M., 36, 100, 227 Portnoy, G. A., 213 Posternak, M. A., 5, 62 Pottash, A. C., 197 Purcell, R., 117 Rae, D. S., 228 Rafanelli, M., 60, 216 Rahman, A., 184, 190 Rai, S. S., 15 Rainey, P. M., 224 Ramana, R., 60, 227 Rapee, R. M., 218 Rapport, D., 229 Rawson, R. A., 208 Ray, S., 3 Reardon, J. P., 219 Recupero, P. R., 225 Reebye, P., 224, 225 Regier, D. A., 155 Reich, D. B., 133 Reichman, C. A., 133 Reid, M. S., 209 Reilly-Harrington, N. A., 87, 99, 224, 227 Reinecke, A., 218 Reisser, A. A., 199 Reiter, S. R., 227 Rejas, J., 153 Reminich, A. N., 214 Ressler, K., 115 Rettig, R., 199 Revicki, D., 230 Reynolds, C. F., 14 Reynolds, V., 235 Riba, M. B., viii, 19, 20 Richardson, M. A., 15 Richardson, R., 115, 218 Rieber, C., 209 Rinaldi, C., 160 Rinne, T., 161, 162 Risch, N., 18 Ritz, L., 232 Roberts, C., 184

Author Index Robinson, P., 220 Rodrigue, J. R., 208 Rodriguez, B. I., vii Rollman, B. L., 108 Roose, S. P., 233 Rosenbaum, J. F., 226, 227 Rosenheck, R. A., 222 Rosenstein, W. S., 96, 182 Rosenthal, M. Z., 133 Rosenthal, N., 220 Rosenthal, R., 62 Rosman, A. S., 208 Rosner, S., 200 Rothbaum, B. O., 115, 225, 226 Rounsaville, B. J., 213 Rovet, J., 226 Royall, R., 15 Roy-Byrne, P. P., 108, 221 Rucker, G., 161 Rudden, S., 225 Ruesink, B., 233 Ruini, C., 216 Rush, A. J., 55, 87, 216, 217, 219, 225, 226, 232, 234 Russell, J. M., 220 Ryan, D., 224, 225 Sachs, G. S., 82, 224, 227 Sackheim, H. A., 15 Safer, D. L., 126 Safren, S. A., 230 Salander-Renberg, 224 Saloman, R. M., 219 Sanchez-Moreno, J., 82 Sanislow, C. A., 218, 233 Sapira, J. D., 207 Sata, M., 208 Sax, K. N., 220 Saxena, S., 212 Saxty, M., 228 Scanley, B. E., 11 Scaramella, L. V., 182 Schalet, B., 232 Schatzberg, A. F., 225, 232 Schene, A. H., 59 Schmaling, K. B., 215 Schmidt, A. B., 211, 230 Schmidtke, A., 224 Schmucker, G., 230 Schneider, F. R., 211 Schneider, J. E., 127 Schofield, N., 211 Schulberg, H. C., 79

Schuster, C. R., 197 Schwartz, J., 14 Schwartz, J. M., 211, 212 Scimeca, M., 199, 201 Scoboria, A., 221 Scott, J., 36, 82, 100, 227, 230 Scott, J. L., 230 Seal, K. H., 215 Segal, Z., 14, 61, 217, 221 Seibyl, J. P., 11 Selin, C. E., 211 Selwyn, S. E., 219 Sengun, S., 223 Sensky, T., 38, 141, 142 Serfaty, M. A., 65 Severe, J., 222, 223 Sharkey, L., 226 Sharma, S. G., 230 Sharp, D., 190 Shea, M. T., 87, 218 Shear, M. K., 3, 79, 108, 113 Shelton, R. C., 64, 159, 216, 219, 222, 232 Sherbourne, C. D., 229 Shirley, E. R., 224 Shoptaw, S. J., 208, 228 Shores-Wilson, K., 232 Shuhaiber, S., 226 Sickel, A. E., 235 Siddle, R., 230 Siegfried, N. M., 204 Sikander, S., 184 Silva, S., 223 Simon, G., 220 Simon, G. E., 36, 56 Simon, N. M., 113, 227 Simons, A. D., 14 Simpson, D. D., 198 Simpson, H. B, 116 Singal, B. M., 235 Singer, L. T., 235 Singer, W., 14 Sit, D. K. Y., 235 Skagerlind, L., 37, 141 Skodol, A. E., 218, 233 Smeenk, S., 233 Smith, J., 155 Smith, N., 81 Smith, P., 224 Smitts, J. A. J., 112 Smolders, M., 77 Smoski, M., 215 Soares, B., 199

241

Sohr-Preston, S. L., 182 Sokol, M. S., 220 Solomon, D. A., 87, 225 Solt, G., 210 Somoza, E. C., 235 Sonnefeld, J., 199 Sorensen, J. L., 207 Sorg, S., 210 Soyka, M., 200 Spasojervic, J., 209 Spiegel, D. A., 113 Spijker, J., 212 Spinhoven, P., 59, 210, 233 Stabl, M., 234 Stang, E. C., 221 Stanton, A., 199 Steel, C., 142 Stefano, S., 136 Stein, M. B., 229 Stein, M. D., 207 Steinberg, J. A., 209 Stephan, A., 162, 169 Stewart, D. Z., 226 Stewart, J. W., 234 Stewart, M. O., 59 Stine, S., 209 Stoessel, P., 212 Stoffers, J. M., 161 Stossel, P. W., 14 Stout, R. L., 218, 225, 233 Stowe, Z. N., 214 Stratkowski, S. M., 220 Streiner, D. L., 221 Strober, M., 123, 127 Stroup, T. S., 222 Strunk, D. N., 59, 61 Suarez, A., 73 Sublette, E. M., 97 Suh, J., 199 Sullivan, G., 229 Sundakov, L., 225 Suppes, T., 183 Suri, R., 214 Surters, P. G., 228 Swartz, M. S., 222 Swift, R. M., 200, 220 Swinson, R. C., 113, 211, 223 Szuba, M. P., 211 Tacchi, M. J., 82 Tahilani, K., 215 Talge, N. M., 183 Tang, T. Z., 61

242

Author Index

Tanikawa, K., 229 Tarrier, N., 73, 141, 142, 211, 235 Tasca, G. A., 121 Taylor, K., 73 Taylor, S., 16 Teasdale, J. D., 227 Telch, C. F., 126 Tell, R. A., 62 ten Doesschate, M. C., 212 Thase, M. E., 14, 57, 216, 219, 220, 224, 225, 226, 227, 229, 235 Theis, J. G. W., 226 Thompson-Brenner, H., 215 Tibaldi, G., 4, 59 Tillfors, M., 217 Timmer, A., 161 Tluczek, A., 184, 190 Tohen, M., 183 Tolin, D. F., 227 Tondo, L., 60, 82, 86, 87, 96, 112, 183, 210 Touyz, S., 225 Trefiglio, R., 124, 125 Trikha, A., 235 Trivedi, M. H., 7, 55, 56, 78, 216, 217, 219, 220, 226, 232 Troxel, A. B., 42 Turk, C. L., 211 Turkington, D., 143, 147, 230 Turner, E. H., 62 Uchimura, Y., 229 Uhl, K., 225 Usten, T. B., 221 Valliant, G. E., 70 Van Balkom, A. J., 114, 210 van den Bergh, B. R., 183 van den Brink, W., 228 van den Hoek, A. J., 207 Van Dyck, R., 210 Van Haastrecht, H. J., 207 Van Heeringen, K., 224 Van Marter, L. J., 213 van Straten, A., 57 Vecchi, S., 198, 200, 206

Vermes, D., 211, 230 Vieta, E., 82 Viguera, A. C., 214 Vitiello, B., 223 Vitonis, A. F., 214 Vittengl, J. R., 59 Vollm, B., 161 Volpicelli, J. R., 196 Volpp, K. G., 42 von Hausswolff-Juhlin, Y., 156 Von Korff, M., 220, 230 Wager, T., 13 Wagner, E., 230 Waikar, S. V., vii Walburton, L. A., 207 Walker, E., 220 Walsh, B. T., 124, 125, 126 Walter, G., 204 Walter, M., 162, 163 Walters, E. E., 55, 221 Warburton, W., 182 Warden, D., 55, 56, 216, 217, 232 Wardle, J., vii, 113 Washton, A. M., 197 Wasserman, D., 224 Watanabe, N., 114 Waternaux, C., 233 Weiler, M. M., 213 Weinberg, I., 218 Weise, J., 220 Weiss, P. M., 225 Weissman, M., 183 Weissman, M. M., 107 Weller, S. B., 208 Wells, K., 223 Wells, V. E., 70 Wensing, M., 77 Wenzel, A., 184, 190 West, S. A., 220 West, S. L., 196 Westen, D., 110 Wettzen, T., 220 Wetzel, R. D., 4 Whittal, M. L., 124 Whitworth, P., 4 Wiegand, F., 220

Willander, A., 210 Williams, R. J., 208 Wilson, G. T., 125, 126, 209, 233 Wilson, L. R., 70 Wimbush, J., 207 Winhusen, T., 209 Winhusen, T. M., 199 Wisner, K. L., 183, 187, 225 Wisniewski, S. R., 55, 56, 216, 217, 224, 227, 229, 232 Wittchen, H. U., 221 Wittknowski, A., 232 Wolpin, J., 226 Woods, S., 3, 113 Worthington, J. J., 226 Wouters, L., 228 Wouters, L. F., 59 Wright, J. H., 5, 6, 27, 57 Wright, J. S., 147 Wright, K., 37, 81, 83 Wu, F. J., 183 Wu, H., 212 Wu, R., 199, 201 Wykes, T., 142 Xie, H., 228 Xie, S. X., 212 Yarmolinsky, A., 199 Yen, S., 218, 233 Young, P. R., 219 Yusupoff, L., 232 Zajecka, J., 220, 226 Zanarini, M. C., 133, 163, 218, 233 Zarkin, G. A., 200 Zhang, H., 227 Zhao, N., 214 Zhu, B., 141 Ziedonis, D. M., 209 Zielezny, M., 60, 216 Zimmerman, M., 5, 62 Zisook, S., 216, 234 Zoellner, L. A., 116 Zwanzger, P., 110 Zweben, A., 201

Combining CBT and Medication: An Evidence-Based Approach by Donna M. Sudak Copyright © 2011 John Wiley & Sons, Inc.

Subject Index Abuse, childhood: and borderline personality, 162 and depression, 57 Academy of Cognitive Therapy, 21 Acamprosate, 194–195, 196, 200–201 ACOG Practice Bulletin, 182 Acute depression, 56–58 Addiction. See Alcohol abuse; Substance abuse Adherence issues: and bipolar disorder, 82–84, 91, 100–101 CBT intervention, 35–37 and depression, 55–56, 59 and eating disorders, 129–132 facilitating compliance, 39–53 overview, 35–37 patient resistance, 36–39 and schizophrenia, 139–140, 141, 144–145, 152 Agranulocytosis, 150 Alcohol abuse. See also Substance abuse CBT efficacy, 200–203 with depression, 77–78 medications for, 194–196 with schizophrenia, 152–154 Alprazolam, 113, 168, 173 American Academy of Pediatrics, 182, 191–192 American Association for the Treatment of Opioid Dependence, 199 American College of Obstetrics and Gynecology (ACOG), 182 American Psychiatric Association, 21 Amphetamines, pregnancy and, 206 Amygdala: fear learning, 106

fluvoxamine effect on, 162 neuroimaging analysis, 13–14 Anhedonia, 63, 67 Anorexia, 119, 120–124. See also Eating disorders Antabuse, 194 Anticholinergics, side effects of, 6 Antidepressants: for anxiety disorders, 110–112 for bipolar disorder, 86, 99 for borderline personality, 161–162, 172 during breastfeeding, 192 for eating disorders, 120–126 efficacy of, 61–63 neuroimaging studies, 17 nonadherence, 36, 45–47, 51–53 for OCD, 116 during pregnancy, 182, 186, 187, 188 for PTSD, 117 side effects of, 6–7 for substance abuse, 202 Antipsychotics: for bipolar disorder, 86 for borderline personality, 161 for eating disorders, 120–121 during pregnancy, 183 for schizophrenia, 139, 156–157 Anxiety disorders: and bipolar disorder, 81–82 with borderline personality, 163 CBT efficacy, 109–117 collaborative care, 103–109 co-morbidity, 107–108, 110–111 and depression, 57, 77–80 depression and, 107–108 lifestyle management, 109 medication caveats, 109–117

243

neuroimaging studies, 13–14, 16 OCD, 116 overview, 103 panic disorder, 112–115 during pregnancy, 183–184 PSTD, 117 research (treatment-efficacy), 2–6 SAD, 115 with substance abuse, 204 treatment analysis, 103–109 Aripiprazole, 161 Association of Behavioral and Cognitive Therapy, 21 Attention-deficit hyperactivity disorder, 84 Aversive agents, goal of, 194–195 Behavioral activation, 67–70, 149 Behavioral techniques, medication adherence, 45–53 Benzodiazepines: for anxiety, 110, 112, 113–114 and borderline personality, 168, 174, 176 during pregnancy, 207 side effects, 6–7, 110, 117 Binge eating, 119. See also Eating disorders Bipolar disorder: with borderline personality, 161, 162, 163 CBT efficacy, 87–90 cognition management, 91–94 collaborative care for, 28, 30 and depression, 63 interpersonal issues, 94–96 manic cycle, managing, 97–99 medication adherence, 36–37, 100–101 overview, 81–82

244

Subject Index

Bipolar disorder (Continued ) during pregnancy, 183, 188, 190–191 rapid-cycling, 99 special challenges, 90–101 with substance abuse, 204 suicide issues, 96–97 treatment analysis, 82–87 Blood abnormalities: with eating disorders, 127 with schizophrenia, 150 Blood glucose, brain function and, 11–12 Blood pressure, orthostatic, 129 BOLD, defined, 13 Bone density issues. See Osteoporosis Borderline personality disorder: collaborative care, 159, 164, 169–180 co-morbid conditions, 162–166 countertransference, 179–180 DBT and, 73, 160, 164–165, 169–180 medication issues, 160–162, 167–175 overview, 159–160 single-provider care, 178–179 special challenges, 167–180 treatment analysis, 160–166 Brain atrophy, eating disorders and, 127 Brain function analysis, 9–18 Breastfeeding issues, 185, 191–192, 207 Bulimia, 119, 124–126. See also Eating disorders Buprenorphine, 196–198, 199, 208 Bupropion, 125, 171 Campral, 194 Cannabis use, 203 Carbamazepine, 173, 194 Cardiac problems: with eating disorders, 126–127, 129 fetal teratogenicity, 186 with schizophrenia, 156 Case management approach, borderline personality, 169–172

CATIE study, 139–140 CBASP, 57 CBT: for anxiety disorders, 109–117 Beck version, x for bipolar disorder, 87–90 for borderline personality, 159–160 brain function analysis, 10, 14–16 in collaborative care, 27–31 computer-assisted, 204 for depression, 56–61, 72–80 for eating disorders, 120–126 medication adjunct, vii–viii, 1–8, 35–53 during pregnancy, 184, 189–192 for schizophrenia, 141–147 for substance abuse, 199–204 Centers for Disease Control (CDC), 194, 207 Childbearing. See Pregnancy Chlorimipramine, 117 Chlorpromazine, 121 Chronic depression, 58 Cigarettes. See Nicotine use Citalopram: for cocaine abuse, 204 for depression, 56 during pregnancy, 186 Clinical Antipsychotic Trials of Intervention Effectiveness, 139–140 Clonazepam, 1, 104–105 Clozapine, 150, 192 Cocaine dependence, 199, 203–204. See also Substance abuse in HIV/AIDS patients, 208 during pregnancy, 206 Cognitive behavioral therapy (CBT). See CBT Cognitive rehearsal, medication adherence, 53 Collaborative treatment: advantages of, 26–27, 29–31 for borderline personality, 159, 164, 169–180 caveats, 31–34 defined, viii, 20 for depression, 63–80

for eating disorders, 119, 126–129, 135, 137 establishing, 20–26 models for, 27–29 overview, 19–20 for schizophrenia, 140, 149, 150–151, 153 Combined treatment. See also CBT; Pharmacotherapy medication reinforcement, 35–53 neurobiology studies, 9–18 reasons for, vii–viii, 1–2 research overview, 2–8 COMBINE study, 200–201 Community Reinforcement Approach (CRA), 208 Co-morbid conditions: with anxiety disorders, 107–109, 110–111 with bipolar disorder, 84, 97 with borderline personality, 162–166 with depression, 64, 77–80 with eating disorders, 119, 121–124 with substance abuse, 194, 204–208 Computer-assisted CBT, 204 Computerized tomography (CT), 9, 12 Confidentiality issues, collaborative care, 25 Coping cards, 52–53, 76 Cost issues, collaborative care, 24 Countertransference: and borderline personality, 179–180 and substance abusers, 208 Credentials, checking, 21, 23 Cyproheptadine, 120–121 DBT. See Dialectical behavior therapy (DBT) D-cycloserine, 114–115 Delusions, schizophrenic, 147–149 Dental problems, eating disorders and, 129 Department of Health and Human Services, 198 Depression: acute, 56–58

Subject Index adherence issues, 6–8, 38, 45–47, 51–53, 55–56 with anxiety, 77–80, 107–108, 110–112 with borderline personality, 161, 162 chronic, 58 collaborative care for, 33–34, 63–80 with eating disorders, 122 medication efficacy, 61–63 neuroimaging studies, 14–18 OCD and, 116 overview, 55–56 patient assessment, 63–64 postpartum, 190–191 during pregnancy, 182–184 recurrent, 58–61 research (treatment-efficacy), 2–6 special challenges, 63–80 with substance abuse, 201–202 suicide issues, 70–77 treatment analysis, 56–61 Diabetes: and eating disorders, 135 with schizophrenia, 156, 157 Diagnoses, accuracy issues, 2 Diagnostic and Statistical Manual of Mental Disorders. See DSM Dialectical behavior therapy (DBT): borderline personality, 160, 164–165, 169–180 collaborative care issues, 26, 31 and suicidal patients, 26, 72–73 Diazepam, 113 Disulfiram, 194–196, 199, 204 Drexel University College of Medicine, ix Drug Enforcement Administration, U.S., 198 Drugs. See Pharmacotherapy; Substance abuse DSM, 2, 37–38, 71 Dual responsibility treatment, defined, 19–20. See also Collaborative treatment Eating disorders: anorexia, 120–124

with borderline personality, 163 bulimia, 124–126 medical issues, 126–129, 132–136 nonadherence, 129–132 overview, 119 relapse issues, 136–137 special challenges, 126–137 treatment analysis, 120–126 Emergency care, collaborative, 25–26 Estrogen replacement, with eating disorders, 121 Ethanol, defined, 195 Exposure treatment: for anxiety, 105–106, 108–109, 111, 114 D-cycloserine and, 114–115 for panic disorder, 34 Family-focused therapy: for bipolar disorder, 83–84 for schizophrenia, 140 FDA, 62, 194–199 Fetal growth, medication effects on, 187 Fluoxetine: for depression, 62 for eating disorders, 122 during pregnancy, 188 for SAD, 115 Fluvoxamine, 162 fMRI, 11–13, 16 Food and Drug Administration. See FDA 48-hour rule, 98 Functional magnetic resonance imaging. See fMRI Genetic factors: in anxiety disorders, 107 in bipolar disorder, 85 Geriatric patients, depression in, 65 HAART, adverse reactions, 197–198 Hallucinations, schizophrenic, 144, 147–149 Hamilton Rating Scale, 62 Hepatitis, 207–208 Heroin, during pregnancy, 206

245

HIV/AIDS, addictions and, 197–198, 207–208 Homework: for anxiety disorder, 106–107 for bipolar patients, 88–89, 100 for depressed patients, 67–70 for eating disorders, 132 for schizophrenia, 144 for substance abuse, 204 Hope box, 73 Hospitalization issues: with borderline personality, 177 in collaborative care, 24 with schizophrenia, 150–152 Hyperlipidemia, 157 Imipramine: for depression, 62 for panic disorder, 3, 4–5, 113 Infections, and eating disorders, 127 Informed consent, in collaborative treatment, 19 Insomnia: and depression, 57, 63 and eating disorders, 127 and schizophrenia, 144 and treatment efficacy, 6 Institute of Medicine, 199 Interferon, caveats, 208 Interoceptive exposure. See Exposure treatment Interpersonal-social rhythm therapy, 83–84 Interpersonal therapy (IPT): advances in, 2 for bipolar disorder, 90–91, 94–96 for borderline personality, 160 for depression, 15–16, 63 efficacy of, 2 during pregnancy, 184, 190 Ipecac, 129 IPT. See Interpersonal therapy (IPT) LAAM, 196 Lamotrigine, 161, 171 Laxative abuse. See Eating disorders

246

Subject Index

Learning ability. See Mental acuity Legal issues, potential, 23, 32, 180 Levo-alpha-acetylmethadol. See LAAM Lithium: for bipolar disorder, 86, 87, 93, 96 during breastfeeding, 192 during pregnancy, 182, 183, 186, 189–191 Lithium nonadherence, 36 Lorazepam, 161, 176 Mania, bipolar, 81, 86, 91–92, 97–99 Matrix model (outpatient treatment), 208 Medical issues: with anxiety disorders, 108, 112 with bipolar disorder, 82 with depression, 55 with eating disorders, 119, 126–136 with schizophrenia, 155–157 with substance abuse, 204–208 Medication. See Pharmacotherapy Memory problems. See Mental acuity Menses, eating disorders and, 127 Mental acuity: in bipolar patients, 81, 93–94 and eating disorders, 127 and schizophrenia, 139, 140, 141, 145, 156 treatment impacts, 6–7 Mentalization therapy, 160 Metabolic syndrome, 157 Methadone: and HIV, 207–208 for opiate addiction, 196–199, 203 during pregnancy, 206 Methamphetamine addiction, 208 MMT, defined, 198 Mood, stabilizing: in bipolar patients, 86–87, 96–97 in borderline personality, 162–164, 176

during pregnancy, 183 for treatment efficacy, 6 MRIs, 9, 12 Naltrexone, 194–195, 196–197, 200–202 National Health Service (U.K.), 142 National Institute on Drug Abuse (NIDA), 193, 198 National Institutes of Health, 208 Nefazodone, 57, 62 Neonatal syndromes, 187–188 Networking. See Collaborative treatment Neurobiology, evidential, 9–18 and anxiety disorders, 13–14 caveats, 11 and depression, 14–16 technology of, 11–13 Neurocognitive development, in utero, 188 Neuroleptics: for borderline personality, 172 for eating disorders, 120–121 Nicotine use: with eating disorders, 124 medication for, 199 during pregnancy, 206 in schizophrenic patients, 153, 157 Nonadherence. See Adherence issues Obsessive-compulsive disorder (OCD): with eating disorders, 123 neuroimaging and, 13–14 treatment for, 116, 117 Office of National Drug Control Policy, 194 Olanzapine, 121, 161 Opiate addiction. See Substance abuse Osteoporosis, eating disorders and, 121, 127 Oxycodone, 173 Panic disorder: with depression, 77–79 treatment for, 112–115, 117 Paroxetine, 15, 62, 187

PET, 11–12, 15 Pharmacotherapy: adherence reinforcement, 35–53 advances in, 2–5 analyzing efficacy of, 8–18 for anxiety disorders, 109–117 benefits of, 49–52 bipolar disorder, 82–84, 100–101 borderline personality, 160–162, 167–175 as CBT adjunct, vii–viii, 1–8 for depression, 61–63 disadvantages of, 6–7 for eating disorders, 120–126 and nonmedical therapists, 33 during pregnancy, 184–192 for schizophrenia, 141–143, 150 for substance abuse, 194–199 Phenylzine, 115 Phobia, specific (PS), 13–14 Physicians, primary care. See Primary care physicians Physicians’ Desk Reference, 182 Pleasant Events Schedule, 69 Polypharmacy issues: and borderline personality, 172–175 with HIV/AIDS, 197–198 and substance abuse, 203 Positive reinforcement, medication, 42 Positron emission tomography. See PET Postpartum issues: with bipolar disorder, 82, 95–96 depression, 184, 191 psychosis, 190–191 screening for, 190–191 Posttraumatic stress disorder (PTSD): with borderline personality, 162 neuroimaging and, 13–14 with substance abuse, 205 treatment for, 117 Pregnancy care: and bipolar disorder, 95–96 breastfeeding issues, 185, 191–192

Subject Index collaborative, 181 and depression, 182–184 fetal growth problems, 187 medication issues, 184–192 neonatal syndromes, 187–188 neurocognitive development, 188 overview, 181–182 postpartum issues, 190–191 risks for mother, 188–189 risks to fetus, 184–188 and schizophrenia, 183 and substance abuse, 205–207 teratogenicity, 185–186 treatment options, 182–184 Prescription drug abuse, 207 Primary care physicians: and anxiety disorders, 108 and borderline personality, 174–175 collaborative treatment role, 19, 33–34 depression management, 64–67 as mental health providers, vii–viii, 1 and panic disorder, vii and schizophrenic patients, 156 Propranolol, 173 Psychiatrists, collaborative role, 19 Psychoeducation: for anxiety disorders, 109 for bipolar disorder, 83–84, 89 for eating disorders, 130–132 for medication adherence, 43–44 for schizophrenia, 145–147, 155 Psychotherapy, analyzing efficacy of, 9–18. See also CBT Radiologic scans, 11–12 Rapid-cycling bipolar disorder, 99 Recurrent depression, 58–61 Regimens, medication adherence, 42 Relapse issues: anxiety disorders, 109 depression and, 58–61 eating disorders, 119, 136–137

and medication adherence, 7–8 residual symptoms and, viii Reminder systems, medication, 41–42 Research, combined treatment. See Combined treatment Residency programs, medical, vii–viii Revia, 194 SAMHSA. See Substance Abuse and Mental Health Services Administration Schema-focused therapy, 160 Schizophrenia: adherence, 37, 139–140, 141, 144–145 CBT efficacy, 143–147 delusions/hallucinations, 147–149 high-risk behaviors, 152–155 hospitalization issues, 150–152 medical issues, 155–157 overview, 139–140 during pregnancy, 183 psychoeducation, 145–147 special challenges, 147–157 with substance abuse, 204, 205 suicide risk, 149–150 symptom management, 149 trauma vulnerability, 152–153 treatment analysis, 141–143 SCID assessment, 163 Selective serotonin reuptake inhibitors. See SSRIs Sequenced Treatment Alternatives to Relieve Depression. See STAR*D study Sertraline: anxiety disorder and, 104, 108, 111 for borderline personality, 165, 168 for depression, 33–34, 65, 68 for SAD, 115 with substance abuse, 201–202 Severe and persistent mental illness. See SPMI, substance abuse and

247

Sexual behavior, high-risk: in schizophrenic patients, 153–154 in substance abusers, 207 Side effects, medication: of antidepressants, 6–7 versus benefits, 43–44, 48–49 and bipolar disorder, 92–93, 100 and borderline personality, 168, 172 and eating disorders, 120, 122–123, 125 and panic disorders, 114 and schizophrenia, 145, 150, 156–157 and substance abuse, 195–198 Single photon emission tomography. See SPECT Single-provider care, borderline personality and, 178–179 Sleep problems. See Schizophrenia SNRIs, 182 Social anxiety disorder (SAD): neuroimaging and, 13–14 treatment for, 115, 117 SPECT, 11–12 Split treatment, defined, 19–20 SPMI, substance abuse and, 204––205 SSRIs: for borderline personality, 161–162 during breastfeeding, 192 and eating disorders, 120, 124–125, 127 effectiveness of, 55 neuroimaging studies, 14 for OCD, 116 during pregnancy, 186, 187, 188 for PTSD, 117 for substance abuse, 199, 202 STAR*D study, 7, 55–56, 62, 78 STEP-BD study, 83 Substance abuse. See also Alcohol abuse adherence issues, 38 alcohol-specific, 194–196, 200–203 with anxiety disorders, 109 with bipolar disorder, 81–82, 84, 97

248

Subject Index

Substance abuse (Continued ) with borderline personality, 161, 163, 168 CBT efficacy, 199–204 with eating disorders, 136 economic costs of, 194 with hepatitis, 207–208 with HIV/AIDS, 207–208 medications for, 194–199 with mental illness, 204–205 opiate-specific, 196–199, 203–204 overview, 193–194 during pregnancy, 205–207 with schizophrenia, 152–155 special challenges, 204–208 treatment analysis, 199–204 Substance Abuse and Mental Health Services Administration, 193, 198 Suicide issues: bipolar disorder, 82, 91, 96–97 borderline personality, 167, 172, 175, 177 depression, 70–77 eating disorders, 119, 127–128 during pregnancy, 183, 188

risk assessment table, 71 schizophrenia, 149–150 substance abuse, 204 treatment strategy table, 74 Survivor kit, 73 TADS study, 3 Tardive dyskinesias, 157 Team-based care. See Collaborative treatment Temazepam, 173 Teratogenicity, 182, 185–186 Thyroxine, 171 Timelines, as therapeutic tools: for bipolar disorder, 88–89 for borderline personality, 163–164 Topirimate: for alcohol abuse, 194 for borderline personality, 161 and eating disorders, 125 Transference-focused therapy, 160 Treatment, mental health. See Combined treatment; Pharmacotherapy Treatment for Adolescents with Depression, 3

Tricyclic antidepressants, 6–7 12-step programs, 201 Two-person feedback rule, 98 Unethical behavior, addressing, 31–32, 180 Valproic acid: for bipolar disorder, 28–29, 86 for borderline personality, 161, 176 Venlafaxine, 15–16, 62, 75 Vitamin deficiencies, 121 Vivitrol, 194 Vomiting, self-induced. See Eating disorders Web sites, specific: Academy of Cognitive Therapy, 21 Association of Behavioral and Cognitive Therapy, 21 reproductive toxicity, 185 Weight issues. See Eating disorders Well-being therapy, 60 Zolpidem, 31