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

Background 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. Aims We compared the 9-year outcomes of individuals initially randomised to clozapine or chlorpromazine. Method 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. Results 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. Conclusions These findings support the comparability in effectiveness between antipsychotic medications but with;lightly greater tolerability of clozapine in the treatment of first-episode psychosis.