Journal
NEUROPSYCHOPHARMACOLOGY
Volume 36, Issue 2, Pages 375-389Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2010.192
Keywords
antimanic; antipsychotic; mania; mood stabilizer; placebo
Categories
Funding
- Actavis-Turkey
- Spanish Ministry of Science and Innovation [2007-0358]
- Centro de Investigacion Biomedica en Red de Salud Mental (CIBERSAM)
- Bruce J Anderson Foundation
- McLean Private Donors' Research Fund
- Actavis
- Ali Raif
- Astra-Zeneca
- Bristol-Myers Squibb
- GlaxoSmithKline
- Janssen-Cilag
- Pfizer
- Sanofi-Aventis
- Servier Corporations
- Eli Lilly
- Actelion
- Essex
- Lundbeck
- Sanofi-Aventis Corporations
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We conducted meta-analyses of findings from randomized, placebo-controlled, short-term trials for acute mania in manic or mixed states of DSM (III-IV) bipolar I disorder in 56 drug-placebo comparisons of 17 agents from 38 studies involving 10 800 patients. Of drugs tested, 13 (76%) were more effective than placebo: aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperdone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone. Their pooled effect size for mania improvement (Hedges' g in 48 trials) was 0.42 (confidence interval (CI): 0.36-0.48); pooled responder risk ratio (46 trials) was 1.52 (CI: 1.42-1.62); responder rate difference (RD) was 17% (drug: 48%, placebo: 31%), yielding an estimated number-needed-to-treat of 6 (all p<0.0001). In several direct comparisons, responses to various antipsychotics were somewhat greater or more rapid than lithium, valproate, or carbamazepine; lithium did not differ from valproate, nor did second generation antipsychotics differ from haloperidol. Meta-regression associated higher study site counts, as well as subject number with greater placebo (not drug) response; and higher baseline mania score with greater drug (not placebo) response. Most effective agents had moderate effect-sizes (Hedges' g=0.26-0.46); limited data indicated large effect sizes (Hedges' g=0.51-2.32) for: carbamazepine, cariprazine, haloperidol, risperidone, and tamoxifen. The findings support the efficacy of most clinically used antimanic treatments, but encourage more head-to-head studies and development of agents with even greater efficacy. Neuropsychopharmacology (2011) 36, 375-389; doi:10.1038/npp.2010.192; published online 27 October 2010
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