Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment

Joseph Patrick McEvoy, Jeffrey A. Lieberman, T. Scott Stroup, Sonia M. Davis, Herbert Y. Meltzer, Robert A. Rosenheck, Marvin S. Swartz, Diana O. Perkins, Richard S.E. Keefe, Clarence E. Davis, Joanne Severe, John K. Hsiao

Research output: Contribution to journalArticle

745 Scopus citations

Abstract

Objective: When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation. Method: Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N= 15], or risperidone [N=16]). Results: Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median= 3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation. Conclusions: For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects.

Original languageEnglish (US)
Pages (from-to)600-610
Number of pages11
JournalAmerican Journal of Psychiatry
Volume163
Issue number4
DOIs
StatePublished - Apr 2006

ASJC Scopus subject areas

  • Psychiatry and Mental health

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    McEvoy, J. P., Lieberman, J. A., Stroup, T. S., Davis, S. M., Meltzer, H. Y., Rosenheck, R. A., Swartz, M. S., Perkins, D. O., Keefe, R. S. E., Davis, C. E., Severe, J., & Hsiao, J. K. (2006). Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. American Journal of Psychiatry, 163(4), 600-610. https://doi.org/10.1176/ajp.2006.163.4.600