Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis

Int J Neuropsychopharmacol. 2010 Feb;13(1):5-14. doi: 10.1017/S1461145709990344. Epub 2009 Jul 29.


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 an 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antidepressive Agents / therapeutic use
  • Antipsychotic Agents / therapeutic use*
  • Aripiprazole
  • Benzodiazepines / therapeutic use
  • Bipolar Disorder / drug therapy*
  • Dibenzothiazepines / therapeutic use
  • Drug Combinations
  • Drug Therapy, Combination
  • Fluoxetine / therapeutic use
  • Humans
  • Olanzapine
  • Piperazines / therapeutic use
  • Placebos
  • Quetiapine Fumarate
  • Quinolones / therapeutic use
  • Randomized Controlled Trials as Topic
  • Treatment Outcome


  • Antidepressive Agents
  • Antipsychotic Agents
  • Dibenzothiazepines
  • Drug Combinations
  • Piperazines
  • Placebos
  • Quinolones
  • olanzapine-fluoxetine combination
  • Fluoxetine
  • Benzodiazepines
  • Quetiapine Fumarate
  • Aripiprazole
  • Olanzapine