Journal
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
Volume 13, Issue 1, Pages 5-14Publisher
OXFORD UNIV PRESS
DOI: 10.1017/S1461145709990344
Keywords
Antipsychotic drugs; bipolar disorder; depression; placebo-controlled trials
Funding
- CIBERSAM (Centro de Investigacion Biomedica en Red de Salud Mental) from the Spanish Ministry of Science and Innovation [CB07/07/0004]
- Spanish Ministry of Science and Innovation, Instituto Carlos III
- Almirall
- AstraZeneca
- Bristol-Myers Squibb
- Eli-Lilly
- European 7th Framework Program
- GlaxoSmithKline
- Janssen-Cilag
- Novartis
- Organon
- Otsuka
- Pfizer
- Sanofi-Aventis
- Seny Foundation
- Servier
- Spanish Ministry of Health (CIBERSAM)
- Spanish Ministry of Science and Education
- Stanley Medical Research Institute
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Randomized, controlled trials have demonstrated efficacy for second-generation antipsychotics in the treatment of acute mania in bipolar disorder. Despite depression being considered the hallmark of bipolar disorder, there are no published systematic reviews or meta-analyses to evaluate the efficacy of modern atypical antipsychotics in bipolar depression. We systematically reviewed published or registered randomized, double-blind, placebo-controlled trials (RCTs) of modern antipsychotics in adult bipolar I and/or II depressive patients (DSM-IV criteria). Efficacy outcomes were assessed based on changes in the Montgomery-Asberg Depression Rating Scale (MADRS) during an 8-wk period. Data were combined through meta-analysis using risk ratio as an effect size with a 95% confidence interval (95% CI) and with a level of statistical significance of 5% (p<0.05). We identified five RCTs; four involved antipsychotic monotherapy and one addressed both monotherapy and combination with art antidepressant. The two quetiapine trials analysed the safety and efficacy of two doses: 300 and 600 mg/d. The only olanzapine trial assessed olanzapine monotherapy within a range of 5-20 mg/d and olanzapine-fluoxetine combination within a range of 5-20 mg/d and 6-12 mg/d, respectively. The two aripiprazole placebo-controlled trials assessed doses of 5-30 mg/d. Quetiapine and olanzapine trials (3/5, 60%) demonstrated superiority over placebo (p<0.001). Only 2/5 (40%) (both aripiprazole trials) failed in the primary efficacy measure after the first 6 wk. Some modern antipsychotics (quetiapine and olanzapine) have demonstrated efficacy in bipolar depressive patients from week 1 onwards. Rapid onset of action seems to be a common feature of atypical antipsychotics in bipolar depression.
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