Second-generation antipsychotic agents in the treatment of acute mania: a systematic review and meta-analysis of randomized controlled trials

Arch Gen Psychiatry. 2007 Apr;64(4):442-55. doi: 10.1001/archpsyc.64.4.442.


Context: Recommendations of treatment guidelines concerning the use of second-generation antipsychotic (SGA) agents for acute mania vary substantially across committees or working groups. Meta-analyses addressing the use of SGAs in the treatment of acute mania are lacking.

Objective: To conduct a meta-analysis of the efficacy and safety of SGAs in the treatment of acute mania.

Data sources: Randomized controlled trials comparing SGAs with placebo, first-generation antipsychotic drugs, or mood stabilizers (MSs) in the treatment of acute mania were searched for in the PsiTri and MEDLINE databases (last search: May 2006).

Study selection: The abstracts, titles, and index terms of studies were searched using the following key words: aripiprazole, amisulpride, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and zotepine in conjunction with mania, manic, and bipolar.

Data extraction: Data on efficacy, global dropout, dropout due to adverse events, dropout due to inefficacy, weight gain, rate of somnolence, and extrapyramidal symptoms were extracted and combined in a meta-analysis.

Data synthesis: A total of 24 studies with 6187 patients were included. The SGAs were significantly more efficacious than placebo. The analysis demonstrated that adding antipsychotic agents to MS treatment was significantly more effective than treatment with MSs alone. The SGAs displayed efficacy comparable with that of MSs. Some SGAs seemed to induce more extrapyramidal symptoms than placebo. The SGAs were also associated with higher rates of somnolence than placebo.

Conclusion: Currently available data suggest that combining SGAs and MSs is the most efficacious treatment of acute mania.

Publication types

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

MeSH terms

  • Acute Disease
  • Adult
  • Anticonvulsants / therapeutic use
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Basal Ganglia Diseases / chemically induced
  • Basal Ganglia Diseases / diagnosis
  • Bipolar Disorder / drug therapy*
  • Drug Therapy, Combination
  • Humans
  • Lithium Compounds / therapeutic use
  • Patient Dropouts
  • Placebos
  • Randomized Controlled Trials as Topic
  • Sleep Wake Disorders / chemically induced
  • Sleep Wake Disorders / diagnosis
  • Treatment Outcome


  • Anticonvulsants
  • Antipsychotic Agents
  • Lithium Compounds
  • Placebos