%0 Journal Article
%T Antipsychotic drugs in first-episode psychosis: a target trial emulation in the FEP-CAUSAL Collaboration.
%A Szmulewicz AG
%A Martínez-Alés G
%A Logan R
%A Ferrara M
%A Kelly C
%A Fredrikson D
%A Gago J
%A Conderino S
%A Díaz-Caneja CM
%A Galvañ J
%A Thorpe L
%A Srihari V
%A Yatham L
%A Sarpal DK
%A Shinn AK
%A Arango C
%A Öngür D
%A Hernán MA
%A Fep-Causal Collaboration OBOT
%J Am J Epidemiol
%V 193
%N 8
%D 2024 Aug 5
%M 38576166
%F 5.363
%R 10.1093/aje/kwae029
%X Good adherence to antipsychotic therapy helps prevent relapses in first-episode psychosis (FEP). We used data from the FEP-CAUSAL Collaboration, an international consortium of observational cohorts, to emulate a target trial comparing antipsychotics, with treatment discontinuation as the primary outcome. Other outcomes included all-cause hospitalization. We benchmarked our results to estimates from the European First Episode Schizophrenia Trial, a randomized trial conducted in the 2000s. We included 1097 patients with a psychotic disorder and less than 2 years since psychosis onset. Inverse-probability weighting was used to control for confounding. The estimated 12-month risks of discontinuation for aripiprazole, first-generation agents, olanzapine, paliperidone, quetiapine, and risperidone were 61.5% (95% CI, 52.5-70.6), 73.5% (95% CI, 60.5-84.9), 76.8% (95% CI, 67.2-85.3), 58.4% (95% CI, 40.4-77.4), 76.5% (95% CI, 62.1-88.5), and 74.4% (95% CI, 67.0-81.2), respectively. Compared with aripiprazole, the 12-month risk differences were -15.3% (95% CI, -30.0 to 0.0) for olanzapine, -12.8% (95% CI, -25.7 to -1.0) for risperidone, and 3.0% (95% CI, -21.5 to 30.8) for paliperidone. The 12-month risks of hospitalization were similar between agents. Our estimates support use of aripiprazole and paliperidone as first-line therapies for FEP. Benchmarking yielded similar results for discontinuation and absolute risks of hospitalization as in the original trial, suggesting that data from the FEP-CAUSAL Collaboration sufficed to remove confounding for these clinical questions. This article is part of a Special Collection on Mental Health.