The International Journal of Neuropsychopharmacology

Review Article

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

Neil D. Woodward a1c1, Scot E. Purdon a2, Herbert Y. Meltzer a3 and David H. Zald a1
a1 Department of Psychology, Vanderbilt University, Nashville, TN, USA
a2 Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada
a3 Department of Psychiatry, Vanderbilt University Medical Center, Nashville, TN, USA

Article author query
woodward nd   [PubMed][Google Scholar] 
purdon se   [PubMed][Google Scholar] 
meltzer hy   [PubMed][Google Scholar] 
zald dh   [PubMed][Google Scholar] 


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.

(Received July 14 2004)
(Reviewed September 28 2004)
(Revised October 21 2004)
(Accepted October 27 2004)

Key Words: Atypical antipsychotics; meta-analysis; neuropsychology; schizophrenia.

c1 Department of Psychology, Vanderbilt University, Nashville, TN, 37203, USA. Tel.: (615) 343-1446 Fax: (615) 343-8449 E-mail: