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Scot E. Purdon, PhD; Barry D. W. Jones, MD; Emanuel Stip, MD; Alan Labelle, MD; Don Addington, MD; Stacy R. David, PhD; Alan Breier, MD; Gary D. Tollefson, MD, PhD; for The Canadian Collaborative Group for Research on Cognition in Schizophrenia

Arch Gen Psychiatry. 2000;57:249-258.

Background  The purpose of this investigation was to test the efficacy of novel antipsychotic medications in the treatment of cognitive impairment in early phase schizophrenia.

Methods  Sixty-five patients in this multicenter double-blind study were randomly assigned to olanzapine (5-20 mg), risperidone (4-10 mg), or haloperidol (5-20 mg). Standard measures of clinical and motor syndromes were administered, as well as a comprehensive battery of tests to assess (1) motor skills, (2) attention span, (3) verbal fluency and reasoning, (4) nonverbal fluency and construction, (5) executive skills, and (6) immediate recall at baseline and after 6, 30, and 54 weeks of treatment.

Results  The general cognitive index derived from the 6 domain scores revealed a significantly greater benefit from treatment with olanzapine relative to haloperidol and olanzapine relative to risperidone, but no significant difference was shown between risperidone and haloperidol. The improvement related to olanzapine was apparent after 6 weeks and enhanced after 30 and 54 weeks of treatment. Exploratory within-group analyses of the 6 cognitive domains after a conservative Bonferroni adjustment revealed a significant improvement with olanzapine only on the immediate recall domain, and similar analyses of the 17 individual tests revealed a significant improvement with olanzapine only on the Hooper Visual Organization Test.

Conclusions  These data suggest that olanzapine has some superior cognitive benefits relative to haloperidol and risperidone. A larger sample replication study is necessary to confirm and generalize the observations of this study and begin evaluation of the implications of this change to cerebral function and quality of life for people with schizophrenia.

From the University of Alberta and Alberta Hospital, Edmonton (Dr Purdon); McMaster University, Hamilton, and Eli Lilly Canada Inc, Scarborough, Ontario (Dr Jones); University of Montreal, Montreal, Quebec (Dr Stip); University of Ottawa and Royal Ottawa Hospital, Ottawa, Ontario (Dr Labelle); University of Calgary, Calgary, Alberta (Dr Addington); and Eli Lilly and Company, Indianapolis, Ind (Drs David, Breier, and Tollefson). A complete list of the members of The Canadian Collaborative Group for Research on Cognition in Schizophrenia can be found below.

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