Antidepressants for the Acute Treatment of Bipolar Depression: A Systematic Review and Meta-Analysis

Objective: The role of antidepressants in the acute treatment of bipolar depression remains a contentious issue. A previous meta-analysis of randomized controlled trials (RCTs) concluded that antidepressants were effective and safe for bipolar depression. Several trials published since then suggest that antidepressants may not be as beneficial as previously concluded. The current systematic review and meta-analyses reexamine the efficacy and safety of antidepressant use for the acute treatment of bipolar depression.

Data Sources: EMBASE, MEDLINE, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials databases were searched for double-blind RCTs published from 2003 to 2009 using the following diagnostic medical subject heading (MESH) terms: bipolar disorder, bipolar depression, bipolar I disorder, bipolar II disorder, bipolar III disorder, bipolar mania, cyclothymia, manic depressive psychosis, mixed mania and depression, and rapid cycling and bipolar disorder. Databases of trial registries were also searched for unpublished RCTs. These searches were supplemented by hand searches of relevant articles and review articles.

Study Selection: Trials that compared acute (< 16 wk) antidepressant treatment with either an active drug or a placebo comparator in adult bipolar patients, depressive phase were eligible for inclusion. Main outcome measures were clinical response, remission, and affective switch.

Data Synthesis: Six RCTs (N = 1,034) were identified since publication in 2004 of the first meta-analysis that assessed antidepressant use in the acute treatment of bipolar depression. These studies were combined with earlier studies for a total of 15 studies containing 2,373 patients. Antidepressants were not statistically superior to placebo or other current standard treatment for bipolar depression. Antidepressants were not associated with an increased risk of switch. Studies that employed more sensitive criteria to define switch did report elevated switch rates for antidepressants.

Conclusions: Although antidepressants were found to be safe for the acute treatment of bipolar depression, their lack of efficacy may limit their clinical utility. Further high-quality studies are required to address the existing limitations in the literature.

J Clin Psychiatry

Submitted: May 23, 2009; accepted August 25, 2009.

Online ahead of print: October 5, 2010 (doi:10.4088/JCP.09r05385gre).

Corresponding author: Michelle M. Sidor, PhD, Department of Psychiatry, University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9070 ([email protected]).