A meta-analysis of neuropsychological change to clozapine, olanzapine, quetiapine, and risperidone in schizophrenia

Int J Neuropsychopharmacol. 2005 Sep;8(3):457-72. doi: 10.1017/S146114570500516X. Epub 2005 Mar 23.


Cognitive impairment is a core feature of schizophrenia and a major impediment to social and vocational rehabilitation. A number of studies have claimed cognitive benefits from treatment with various atypical antipsychotic drugs (APDs). The currently available evidence supporting cognitive improvement with atypical APDs was evaluated in two meta-analyses. Studies that (1) prospectively examined cognitive change to the atypical APDs clozapine, olanzapine, quetiapine, and risperidone, (2) included a commonly used neuropsychological test, and (3) provided data from which relevant effect sizes could be calculated, were included. Forty-one studies met these criteria. Neuropsychological test data from each study were combined into a Global Cognitive Index and nine cognitive domain scores. Two meta-analyses were carried out. The first included 14 controlled, random assignment trials that assigned subjects to an atypical APD and a typical APD control arm. The second analysis included all prospective investigations of atypical treatment and the within-group change score divided by its standard deviation served as an estimate of effect size (ES). The first analysis revealed that atypicals are superior to typicals at improving overall cognitive function (ES=0.24). Specific improvements were observed in the learning and processing speed domains. The second analysis extended the improvements to a broader range of cognitive domains (ES range=0.17-0.46) and identified significant differences between treatments in attention and verbal fluency. Moderator variables such as study blind and random assignment influence results of cognitive change to atypical APDs. Atypical antipsychotics produce a mild remediation of cognitive deficits in schizophrenia, and specific atypicals have differential effects within certain cognitive domains.

Publication types

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

MeSH terms

  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines / therapeutic use
  • Clozapine / therapeutic use
  • Dibenzothiazepines / therapeutic use
  • Humans
  • MEDLINE / statistics & numerical data
  • Neuropsychological Tests / statistics & numerical data*
  • Olanzapine
  • Quetiapine Fumarate
  • Risperidone / therapeutic use
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology
  • Schizophrenic Psychology*
  • Treatment Outcome


  • Antipsychotic Agents
  • Dibenzothiazepines
  • Benzodiazepines
  • Quetiapine Fumarate
  • Clozapine
  • Risperidone
  • Olanzapine