Negative Prognostic Effect of Baseline Antipsychotic Exposure in Clinical High Risk for Psychosis (CHR-P): Is Pre-Test Risk Enrichment the Hidden Culprit?

Introduction: Sample enrichment is a key factor in contemporary early-detection strategies aimed at the identification of help-seekers at increased risk of imminent transition to psychosis. We undertook a meta-analytic investigation to ascertain the role of sample enrichment in the recently highlighted negative prognostic effect of baseline antipsychotic (AP) exposure in clinical high-risk (CHR-P) of psychosis individuals. Methods: Systematic review and meta-analysis of all published studies on CHR-P were identified according to a validated diagnostic procedure. The outcome was the proportion of transition to psychosis, which was calculated according to the Freeman-Tukey double arcsine transformation. Results: Thirty-three eligible studies were identified, including 16 samples with details on AP exposure at baseline and 17 samples with baseline AP exposure as exclusion criterion for enrollment. Those with baseline exposure to AP (n = 395) had higher transition rates (29.9%; 95% CI: 25.1%-34.8%) than those without baseline exposure to AP in the same study (n = 1289; 17.2%; 15.1%-19.4%) and those coming from samples that did not include people who were exposed to AP at baseline (n = 2073; 16.2%; 14.6%-17.8%; P <. 05 in both the fixed-effects and the random-effects models). Heterogeneity within studies was substantial, with values above 75% in all comparisons. Conclusions: Sample enrichment is not a plausible explanation for the higher risk of transition to psychosis of CHR-P individuals who were already exposed to AP at the enrollment in specialized early-detection programs. Baseline exposure to AP at CHR-P assessment is a major index of enhanced, imminent risk of psychosis.