Clozapine v. chlorpromazine in treatment-naive, first-episode schizophrenia: 9-year outcomes of a randomised clinical trial
Ragy R. Girgis, Michael R. Phillips, Xiaodong Li, Kejin Li, Huiping Jiang, Chengjing Wu, Naihua Duan, Yajuan Niu, Jeffrey A. Lieberman
  • Declaration of interest

    R.R.G. has received research support from Janssen and Lilly through APIRE and a travel stipend from Lilly, Forest, and Elsevier Science through the Society of Biological Psychiatry. N.D. has received research support from Pfizer. J.A.L. has received research grant support from Acadia, Allon, AstraZeneca, Bristol-Myers Squibb, Forest Labs, GlaxoSmithKline, Janssen, Merck, Organon, Pfizer, and Wyeth. He has acted as a consultant and an advisory board member for Astra-Zeneca, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly, and Pfizer; has been a consultant for Cephalon, Johnson & Johnson and Novartis; an advisory board member for Bioline, Forest Labs, Lundbeck, Organon and Wyeth; and a DSMB member for Solvay. J.A.L. has received no direct financial compensation or salary support for participation in research, consulting, advisory board or DSMB activities. J.A.L. holds a patent from Repligen.



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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