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Bipolar depression and substance abuse

Vol. 4, No. 9 / September 2005

Lee S. Altman, MD, offers a cogent review of the risks and benefits associated with use of antidepressants to treat bipolar depression (Current Psychiatry, July 2005).

The article, however, did not address the role of comorbid substance abuse, which may increase morbidity in bipolar patients taking antidepressants. Substance abuse can increase the risk of acute switch to mania, but may easily be overlooked.

For example, a recent meta-analysis found no risk of manic switch when a mood stabilizer/antidepressant combination was used to treat bipolar depression. But like most clinical trials, all 12 studies reviewed in this meta-analysis excluded patients with substance abuse.1

By contrast, a study of bipolar patients that included substance abusers2 found that:

  • more than one-half of patients with comorbid substance abuse had a history of antidepressant-induced mania or hypomania
  • 29% experienced an antidepressant-induced switch even while receiving a concomitant mood stabilizer.

Approximately 60% of patients with bipolar type I disorder abuse substances at some point,3 so most bipolar patients will face this problem. This high prevalence, coupled with the fact that substance abuse comorbidity increases the risks associated with antidepressant use, reinforces the need for caution when treating bipolar depression.

Daniel Z. Lieberman, MD
Associate professor of psychiatry
and behavioral sciences
Director, Clinical Psychiatric Research Center
George Washington University
School of Medicine
Washington, DC


  1. Gijsman HJ, Geddes JR, Rendell JM, et al. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry 2004;161:1537-47.
  2. Goldberg JF, Whiteside JE. The association between substance abuse and antidepressant-induced mania in bipolar disorder: a preliminary study. J Clin Psychiatry 2002;63:791-5.
  3. Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study. JAMA 1990; 264:2511-8.

Dr. Altman responds

Dr. Lieberman correctly highlights the important role of comorbid substance abuse with bipolar disorder. In fact, we both referenced the Goldberg-Whiteside study demonstrating the increased risk of antidepressant-induced mania among bipolar patients with comorbid substance abuse. This is one of many risk factors for switching mentioned in my article.1

Clearly, comorbid substance abuse is an important consideration when deciding whether to use antidepressants to treat bipolar depression.

Lee S. Altman, MD
Assistant professor of psychiatry
University of Colorado Health Sciences Center, Denver


  1. Goldberg JF, Truman CJ. Antidepressant-induced mania: an overview of current controversies. Bipolar Disorders 2003;5:407-20.

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