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Br J Psychiatry. 2011 Oct;199(4):281-8. doi: 10.1192/bjp.bp.110.081471.

Clozapine v. chlorpromazine in treatment-naive, first-episode schizophrenia: 9-year outcomes of a randomised clinical trial.

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  • 1Department of Psychiatry, Columbia University, College of Physicians & Surgeons and New York State Psychiatric Institute, New York, USA.



The differential effects of so-called 'first- and second generation' antipsychotic medications, when given in the first episode, on the long-term outcome of schizophrenia remain to be elucidated.


We compared the 9-year outcomes of individuals initially randomised to clozapine or chlorpromazine.


One-hundred and sixty individuals with treatment-naive, first episode schizophrenia or schizophreniform disorder in a mental health centre in Beijing, China were randomised to clozapine or chlorpromazine treatment for up to 2 years,followed by up to an additional 7 years of naturalistic treatment. The primary outcome was remission status for individuals in each group.


Individuals in both groups spent essentially equal amounts of time in each clinical state over the follow-up time period(remission, 78%; intermediate, 8%; relapse, 14%). There were no significant differences on other measures of illness severity. The clozapine group was more likely than the chlorpromazine group to remain on the medication to which they were originally assigned (26% v. 10%, P = 0.01). There were no significant differences between the two groups on other secondary efficacy outcomes.


These findings support the comparability in effectiveness between antipsychotic medications but with slightly greater tolerability of clozapine in the treatment of first-episode psychosis.

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