Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder

Jan Volavka, Pal Czobor, Brian Sheitman, Jean Pierre Lindenmayer, Leslie Citrome, Joseph P. McEvoy, Thomas B. Cooper, Miranda Chakos, Jeffrey A. Lieberman

Research output: Contribution to journalArticle

369 Scopus citations


Objective: The authors compared the efficacy and safety of three atypical antipsychotics (clozapine, olanzapine, and risperidone) with one another and with haloperidol in the treatment of patients with chronic schizophrenia or schizoaffective disorder. Method: In a double-blind trial, 157 inpatients with a history of suboptimal treatment response were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol for 14 weeks (an 8-week escalation and fixeddose period followed by a 6-week variable-dose period). Results: Clozapine, risperidone, and olanzapine (but not haloperidol) resulted in statistically significant improvements in total score on the Positive and Negative Syndrome Scale. Improvements seen in total and negative symptom scores with clozapine and olanzapine were superior to haloperidol. The atypical drugs, particularly olanzapine and clozapine, were associated with weight gain. Conclusions: The effects of atypical antipsychotics in this population were statistically significant but clinically modest. The overall pattern of results suggests that clozapine and olanzapine have similar general antipsychotic efficacy and that risperidone may be somewhat less effective. Clozapine was the most effective treatment for negative symptoms. However, the differences among treatments were small.

Original languageEnglish (US)
Pages (from-to)255-262
Number of pages8
JournalAmerican Journal of Psychiatry
Issue number2
Publication statusPublished - Feb 16 2002
Externally publishedYes


ASJC Scopus subject areas

  • Psychiatry and Mental health

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