Original Investigation

Clozapine After 1 Failed Antipsychotic Drug Trial in First-Episode Psychosis

JAMA Psychiatry 10.1001/jamapsychiatry.2026.0086

March 11, 2026 at 11:00 AM EDT

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Is clozapine more efficacious than olanzapine or amisulpride in patients who fail to respond to an initial antipsychotic drug trial?In this randomized clinical trial including 654 participants, clozapine was found to be more efficacious than olanzapine or amisulpride, and there was no clear difference in all-cause treatment discontinuation between treatment groups.Clozapine may be considered as a preferred subsequent option for patients with first-episode psychosis who have not responded to an initial antipsychotic drug.

Corresponding Authors: Stefan Leucht, PhD, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Str 22, Munich, Bavaria 81675, Germany (stefan leucht@tum.de); Dengtang Liu, MD, PhD, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Rd, Shanghai 200030, China (liudengtang@smhc.org.cn).

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