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Clinical Highlights in Bipolar Depression: Focus on Atypical Antipsychotics

Joseph R. Calabrese, MD; Omar Elhaj, MD; Prashant Gajwani, MD; and Keming Gao, MD

Published: June 15, 2005

Article Abstract

Despite the considerable burden of bipolar depression, the treatment of this debilitating phase of bipolardisorder is suboptimally addressed by currently available pharmacologic options. Consequently,there is a need for the development of new treatment options with enhanced efficacy and tolerability.Evidence of antidepressant efficacy for some of the atypical antipsychotics in the treatment of bipolardepression has recently emerged. The findings of a large-scale, placebo-controlled, double-blind, randomizedclinical study of olanzapine alone and in combination with fluoxetine, and a similar study ofquetiapine monotherapy, suggest that some of the atypical antipsychotics may be efficacious in treatingdepressive symptoms in patients with bipolar I disorder. Subpopulation analyses suggest that quetiapinemonotherapy and the olanzapine plus fluoxetine combination appear to be effective in treating depressionin patients with a rapid-cycling course. The magnitude of improvement in depressive symptoms inthe bipolar I population appears to be larger for quetiapine monotherapy compared with either olanzapineor olanzapine plus fluoxetine; however, the limitations of such a cross-study comparison are acknowledged.Both olanzapine monotherapy and combination therapy, as well as quetiapine monotherapy,were well tolerated. The overall incidence of treatment-emergent mania was low and comparablewith placebo in both studies. Somnolence, weight gain, increased appetite and nonfasting glucose andcholesterol levels were more commonly reported in patients treated with olanzapine monotherapy orcombination therapy compared with placebo. Dry mouth, sedation/somnolence, dizziness, and constipationwere more commonly associated with quetiapine treatment. Large, controlled studies are needed todetermine whether other psychotropic agents have antidepressant properties that would make them suitablefor use in patients with bipolar depression. In addition, direct comparison of the regimens used inthe current study should determine whether the differences evident between them can be confirmed.

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