The Pharmacologic Treatment of Bipolar DisorderEffective Agents in Treating Bipolar Depression

Gary S. Sachs, MD; Jamie M. Dupuy, MD; and Curtis W. Wittmann, MD

Published: May 15, 2011

Article Abstract

Over the past half century, substantial clinical trial data have accumulated to guide clinical management of bipolar disorder, and 13 medications have gained US Food and Drug Administration approval for the treatment of mania or bipolar depression or the maintenance treatment of bipolar disorder. While the number of studies has grown and many controversies related to pharmacologic treatment of bipolar disorder are not yet resolved, the task of transforming the accumulated evidence into useful guidance for clinical practice becomes more manageable and less error prone by limiting consideration to the highest quality studies. Therefore, this article emphasizes points of relative clarity by highlighting findings supported by double-blind, placebo-controlled clinical trials with samples of at least 100 subjects. A MEDLINE search was conducted and augmented by a manual search of bibliographies, textbooks, and abstracts from recent scientific meetings for randomized controlled trials published in English between 1950 and April 2010 with at least 100 subjects. Keywords used in the search included randomized controlled trial, mania, hypomania, depression, relapse prevention, placebo, antidepressant, switch, and maintenance treatment of bipolar disorder. A paradigm for implementing evidence-based treatment is offered along with consideration of patterns emerging across clinical trials.

J Clin Psychiatry 2011;72(5):704-715

Submitted: August 24, 2011; accepted March 29, 2011 (doi:10.4088/JCP.10m06523).

Corresponding author: Gary S. Sachs, MD, Massachusetts General Hospital, Clinical Psychopharmacology Unit, WACC 815, 50 Staniford St, Boston, MA 02114 (

Volume: 72

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