Typical and Atypical Antipsychotics in Bipolar Depression

Keming Gao, M.D., Ph.D.; Prashant Gajwani, M.D.; Omar Elhaj, M.D.; and Joseph R. Calabrese, M.D.

Background: Symptomatic bipolar patients experience more depressive than manic symptoms, but fewer studies have been designed for bipolar depression than for bipolar mania. Since the antipsychotic agents have been shown to diminish depressive symptoms during the treatment of mania, atypical agents are now being studied for use in bipolar depression.

Data Sources: English-language articles published from 1980 through July 2004 and cited in MEDLINE were searched using the keywords antipsychotics, typical antipsychotics, atypical antipsychotics, bipolar depression, bipolar disorder, manic-depressive illness, placebo, and clinical trial. The generic and brand names of individual antipsychotics were also entered as keywords. Peer-reviewed abstracts of placebo-controlled studies assessing acute or long-term efficacy in bipolar depression presented at major scientific meetings were also reviewed.

Study Selection: Use of a depression rating scale was required for inclusion of studies of the atypical antipsychotic agents in our analysis.

Data Synthesis: Twenty-one randomized trials and 13 nonrandomized prospective trials were identified. In the only 2 acute, double-blind, placebo-controlled studies of antipsychotics in bipolar depression, the effect size of olanzapine was small (0.32) compared with the effect sizes of quetiapine (0.91-1.09, depending on dose). The effect size in acute mania of olanzapine at week 4 and quetiapine at week 3 was 0.50 and 0.39, respectively. Both olanzapine and quetiapine have been shown to be superior to placebo in the acute treatment of bipolar I depression. In addition, olanzapine has been shown to be more effective than placebo in delaying relapse into bipolar depression. With the exception of a 6-month perphenazine study, there are no other randomized studies of typical antipsychotics that support the conclusion that this class of medication worsens bipolar depression.

Conclusion: Emerging data suggest that the atypical antipsychotic agents have a role in the acute and long-term treatment of bipolar depression. No convincing data support the impression that the typical antipsychotic agents worsen bipolar depression.

(J Clin Psychiatry 2005;66:1376-1385)

Received Sept. 27, 2004; accepted April 13, 2005. From the Department of Psychiatry, University Hospitals of Cleveland, Case Western Reserve University, School of Medicine, Cleveland, Ohio.

Support for this article included grant P20 MH-66054 from the National Institute of Mental Health (Dr. Calabrese).

Dr. Gajwani has served on the speakers bureau for Bristol-Myers Squibb, Pfizer, Wyeth, and Forest. Dr. Elhaj has been a consultant for, has received honoraria from, and has served on the speakers or advisory board for AstraZeneca. Dr. Calabrese has received grant support and honoraria from Abbott, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly, Pfizer, and Janssen; has received funding from Merck; and has had consulting agreements and/or has served on advisory boards for Abbott, AstraZeneca, Bristol-Myers Squibb/Otsuka, Eli Lilly, GlaxoSmithKline, Janssen, and Teva. Dr. Gao reports no other financial affiliation or relationship relevant to the subject of this article.

Corresponding author and reprints: Keming Gao, M.D., Ph.D., Mood Disorders Program, 11400 Euclid Avenue, Suite #200, Cleveland, OH 44106 (e-mail: keming.gao@uhhs.com).