Self-Reported History of Manic/Hypomanic Switch Associated With Antidepressant Use: Data From the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)

Christine J. Truman, M.D.; Joseph F. Goldberg, M.D.; S. Nassir Ghaemi, M.D., M.P.H.; Claudia F. Baldassano, M.D.; Stephen R. Wisniewski, Ph.D.; Ellen B. Dennehy, Ph.D.; Michael E. Thase, M.D.; and Gary S. Sachs, M.D.

Objective: Antidepressant safety and efficacy remain controversial for the treatment of bipolar depression. The present study utilized data from the National Institute of Mental Health Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) to examine the prevalence and clinical correlates of self-reported switch into mania/hypomania during antidepressant treatment.

Method: Antidepressant treatment histories were examined from intake assessments for the first 500 subjects enrolled into the STEP-BD between November 1999 and November 2000. Affective switch was defined as a report of mania, hypomania, or mixed episodes within the first 12 weeks of having started an antidepressant. Demographic and clinical characteristics were compared for subjects with or without a history of acute switch during antidepressant treatment.

Results: Among the 338 subjects with prior antidepressant treatment and complete data on switch event outcomes, 44% reported at least 1 such occurrence. Patients with a shorter duration of illness (odds ratio [OR] = 1.02, 95% CI = 1.01 to 1.04) and a history of multiple antidepressant trials (OR = 1.73, 95% CI = 1.38 to 2.16) were more likely to report a history of switch than other patients. A significantly increased risk for affective polarity switch was identified in patients who had ever switched to mania/hypomania while taking tricyclic antidepressants (OR = 7.80, 95% CI = 1.56 to 28.9), serotonin reuptake inhibitors (OR = 3.73, 95% CI = 1.98 to 7.05), or bupropion (OR = 4.28, 95% CI = 1.72 to 10.6). Switch was less common during treatment with electroconvulsive therapy or monoamine oxidase inhibitors than other antidepressants.

Conclusions: Antidepressants are associated with the potential risk for treatment-emergent mania or hypomania, particularly in bipolar patients with short illness duration, multiple past antidepressant trials, and past experience of switch with at least one antidepressant.

(J Clin Psychiatry 2007;68:1472-1479)

Received Jan. 3, 2007; accepted March 26, 2007. From Finney Psychotherapy Associates, Norfolk, Va. (Dr. Truman); the Affective Disorders Program, Silver Hill Hospital, New Canaan, Conn., and the Department of Psychiatry, Mount Sinai School of Medicine, New York N.Y. (Dr. Goldberg); the Department of Psychiatry and Behavioral Sciences, Bipolar Disorder Research Program, Emory University, Atlanta, Ga. (Dr. Ghaemi); the Department of Psychiatry, the University of Pennsylvania, Philadelphia (Drs. Baldassano and Thase); University of Pittsburgh Medical Center and the Western Psychiatric Institute and Clinic, Pittsburgh, Pa. (Drs. Wisniewski and Thase); the Department of Psychological Sciences, Purdue University, West Lafayette, Ind. (Dr. Dennehy); and the Department of Psychiatry, Partners Bipolar Treatment Center, Massachusetts General Hospital, Harvard Medical School, Boston (Dr. Sachs).

This project has been funded in whole or in part by the National Institute of Mental Health (NIMH), National Institutes of Health, under contract N01MH80001.

Presented in part at the 156th annual meeting of the American Psychiatric Association, San Francisco, Calif., May 17-21, 2003.

Acknowledgments appear at the end of the article.

Any opinions, findings, and conclusions or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the NIMH.

Financial disclosure appears at the end of the article.

Corresponding author and reprints: Joseph F. Goldberg, M.D., Silver Hill Hospital, 208 Valley Rd., New Canaan, CT 06840 (e-mail: JFGoldberg@yahoo.com).