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Articles   |    
Do Comorbid Anxiety Disorders Moderate the Effects of Psychotherapy for Bipolar Disorder? Results From STEP-BD
Thilo Deckersbach, Ph.D.; Amy T. Peters, B.A.; Louisa Sylvia, Ph.D.; Anna Urdahl, B.A.; Pedro V.S. Magalhães, M.D., Ph.D.; Michael W. Otto, Ph.D.; Ellen Frank, Ph.D.; David J. Miklowitz, Ph.D.; Michael Berk, M.D., Ph.D.; Gustavo Kinrys, M.D.; Andrew Nierenberg, M.D.
Am J Psychiatry 2014;171:178-186. doi:10.1176/appi.ajp.2013.13020225
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Dr. Deckersbach has received honoraria, consultation fees, and/or royalties from Boston University, BrainCells, the Catalan, Massachusetts General Hospital Psychiatry Academy, and Systems Research and Applications Corporation. Dr. Sylvia has served as a consultant to Bracket and Clintara and received royalties from New Harbinger. Dr. Otto has served as a consultant to MicroTransponder and has received research support from NIMH and royalties from Oxford University Press and Routledge. Dr. Frank has received research support or royalties from American Psychological Association Press, Guilford Press, Lundbeck, and Servier International. Dr. Miklowitz has received research grant support from the Attias Family Foundation, the Brain and Behavior Research Foundation, the Danny Alberts Foundation, the Deutsch, Kayne, and Knapp Foundations, and NIMH, and he has received royalties from Guilford Press and John Wiley and Sons. Dr. Berk has received research support from the Autism Foundation, the Australia National Health and Medical Research Council, Beyond Blue, Bristol-Myers Squibb, Cooperative Research Centre, Eli Lilly, the Geelong Medical Research Foundation, GlaxoSmithKline, Mayne Pharma, Medical Benefits Fund, Meat and Livestock Board, NIH, Novartis, Organon, Rotary Health, Servier, Simons Cancer Council of Victoria, Stanley Medical Research Foundation, and Woolworths and has served as a speaker for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay, and Wyeth and a consultant to AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen Cilag, Lundbeck, Merck, and Servier. Dr. Kinrys has received research support from Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, Sanofi Synthelabo, Sepracor, Pfizer, UCB Pharma, and Wyeth-Ayerst Laboratories, advisory and consulting fees from AstraZeneca, Cephalon, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica, Pfizer, Sepracor, UCB Pharma, and Wyeth-Ayerst Laboratories, and speaker’s fees from AstraZeneca, Forest Pharmaceuticals, GlaxoSmithKline, Sepracor, and Wyeth-Ayerst Laboratories. Dr. Nierenberg is a consultant for Abbott Laboratories, AstraZeneca, Basilea, BrainCells, Brandeis University, Bristol-Myers Squibb, Cephalon, Corcept, Eli Lilly, Forest, Genaissance, GlaxoSmithKline, Innapharma, Janssen Pharmaceutica, Jazz Pharmaceuticals, Lundbeck, Merck, Novartis, Pamlab, PGx Health, Pfizer, Ridge Diagnostics, Roche, Schering-Plough, Sepracor, Shire, Somerset, Sunovion, Takeda, Targacept, and Teva, and he receives research support from the Agency for Healthcare Research and Quality, Bristol-Myers Squibb, Cederroth, Cyberonics, Elan, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica, Lichtwer Pharma, Mylin, NARSAD, NIMH, Pamlab, Pfizer, Shire, the Stanley Foundation, and Wyeth-Ayerst and honoraria from the American Drug Utilization Review Society, the American Society for Clinical Psychopharmacology, AstraZeneca, Biomedical Development, Boston Center for the Arts, Brandeis University, Eli Lilly, Forest, the Harold Grinspoon Charitable Foundation, Health New England, Janssen, International Society for Bipolar Disorder, Massachusetts General Hospital Psychiatry Academy, Mid-Atlantic Permanente Research Institute, Second Meeting of East Asian Bipolar Forum, University of Pisa, University of Texas Southwestern Medical Center, University of Wisconsin at Madison, and Zucker Hillside Hospital and other income from Belvior Publications, Controlled Risk Insurance Company, MBL Publishing, and Slack, and he holds a joint ownership copyright with Massachusetts General Hospital for the Structured Clinical Interview for the Montgomery Åsberg Depression Rating Scale and the Clinical Positive Affect Scale and is a stakeholder with Appliance Computing (MindSite), Brain Cells, and InfoMed.

STEP-BD was funded in part by NIMH contract N01MH80001. Support for the development of the psychosocial treatments was provided by NIMH grants MH-29618 (to Dr. Frank) and MH-43931 and MH-55101 (to Dr. Miklowitz), as well as NARSAD (to Dr. Miklowitz). Supported in part by a K-23 NIMH Career Award (1K23MH074895-01A2) and grants from NARSAD, International OCD Foundation, Tourette Syndrome Association, and Tufts University (to Dr. Deckersbach).

From the Department of Psychiatry, Massachusetts General Hospital, Boston; Harvard Medical School, Boston; the Department of Psychiatry, University of Illinois at Chicago; the National Institute for Translational Medicine, Hospital de Clínicas de Porto Alegre, Brazil; Boston University; the University of Pittsburgh; School of Medicine, University of California, Los Angeles; Deakin University, Melbourne, Australia; and the University of Melbourne, Melbourne, Australia.

Address correspondence to Dr. Deckersbach (tdeckersbach@partners.org).

Copyright © 2014 by the American Psychiatric Association

Received February 18, 2013; Revised May 27, 2013; Accepted June 17, 2013.

Abstract

Objective  At least 50% of individuals with bipolar disorder have a lifetime anxiety disorder. Individuals with both bipolar disorder and a co-occurring anxiety disorder experience longer illness duration, greater illness severity, and poorer treatment response. The study explored whether comorbid lifetime anxiety in bipolar patients moderates psychotherapy treatment outcome.

Method  In the Systematic Treatment Enhancement Program randomized controlled trial of psychotherapy for bipolar depression, participants received up to 30 sessions of intensive psychotherapy (family-focused therapy, interpersonal and social rhythm therapy, or cognitive-behavioral therapy) or collaborative care, a three-session comparison treatment, plus pharmacotherapy. Using the number needed to treat, we computed effect sizes to analyze the relationship between lifetime anxiety disorders and rates of recovery across treatment groups after 1 year.

Results  A total of 269 patients (113 women) with a comorbid lifetime anxiety disorder (N=177) or without a comorbid lifetime anxiety disorder (N=92) were included in the analysis. Participants with a lifetime anxiety disorder were more likely to recover with psychotherapy than with collaborative care (66% compared with 49% recovered over 1 year; number needed to treat=5.88, small to medium effect). For patients without a lifetime anxiety disorder, there was no difference between rates of recovery in psychotherapy compared with collaborative care (64% compared with 62% recovered; number needed to treat=50, small effect). Participants with one lifetime anxiety disorder were likely to benefit from intensive psychotherapy compared with collaborative care (84% compared with 53% recovered; number needed to treat=3.22, medium to large effect), whereas patients with multiple anxiety disorders exhibited no difference in response to the two treatments (54% compared with 46% recovered; number needed to treat=12.5, small effect).

Conclusions  Depressed patients with bipolar disorder and comorbid anxiety may be in particular need of additional psychotherapy for treating acute depression. These results need to be replicated in studies that stratify bipolar patients to treatments based on their anxiety comorbidity status.

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FIGURE 1. Differential Treatment Effects of Psychotherapy and Collaborative Care for Bipolar Patients With and Without a Lifetime Anxiety Disorder
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TABLE 1.Demographic and Clinical Characteristics of 269 Bipolar Depressed Patients With and Without a Lifetime Anxiety Disorder
Table Footer Note

aDepressive severity refers to the summary score of depression symptoms from the Clinical Monitoring Form recorded within 1 week of the date of randomization to treatment.

Table Footer Note

bMania severity refers to the summary score of mania symptoms from the Clinical Monitoring Form recorded within 1 week of the date of randomization to treatment.

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TABLE 2.Moderator Effects of Comorbid Anxiety Disorders on Collaborative Care and Psychotherapy for Bipolar Depression
Table Footer Note

aStandard error reported is for the responder rate difference.

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TABLE 3.Moderator Effects of Specific Anxiety Disorders on Collaborative Care and Psychotherapy for Bipolar Depression
Table Footer Note

aStandard error reported is for the responder rate difference.

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TABLE 4.Moderator Effects of the Number of Anxiety Disorders on Collaborative Care and Psychotherapy for Bipolar Depression
Table Footer Note

aStandard error reported is for the responder rate difference.

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