Transient pre-baseline antipsychotic exposure (TPAE) is a prognostic specifier in clinical high risk for psychosis: evidence from the PSYSCAN consortium study

Baseline exposure to antipsychotics (AP) in individuals at clinical high risk for psychosis (CHR-P) has emerged as a robust prognostic marker for transition to psychosis. Recent meta-analyses show that CHR-P individuals receiving APs at study entry exhibit significantly higher transition rates, with a temporally discernible dose-effect pattern. To test the replicability of this prognostic signal, we conducted a secondary analysis of publicly available supplementary data from the PSYSCAN Consortium. Despite applying strict inclusion criteria that limited AP exposure to ≤30 days of low-dose treatment, transition rates in PSYSCAN remained higher in the AP-exposed group (28.0% vs. 12.2%; RR 2.29). Notably, this finding was not emphasized in the primary publication, thus representing inadvertent yet compelling support for the prognostic relevance of early AP need. These results reinforce the rationale for future CHR-P studies to adopt AP-naïve condition as a stratification criterion to avoid pharmacologically induced diagnostic obscuration and improve the precision of risk modelling. Furthermore, they corroborate the PSYSCAN-derived operational notion of transient pre-baseline AP exposure (TPAE) (i.e., ≤30 cumulative days in the 3 months preceding baseline, at subtherapeutic doses) as a pragmatic and testable prognostic specifier that supplements existing CHR-P criteria.