Lack of transparency on baseline pharmacological treatments in Clinical High-Risk for psychosis (CHR-P) may degrade precision: A systematic review and meta-analysis

The field of Clinical High-Risk for Psychosis (CHR-P) is a dynamic area within contemporary psychiatry and serves as a crucial testing ground for precision prognostic models. Nonetheless, some foundational aspects remain inadequately conceptualized and consequently not transparently reported, such as baseline pharmacotherapy. A systematic review and meta-analysis were conducted by searching the MEDLINE and Cochrane Library databases for studies published up to August 31, 2024. Eligible studies included CHR-P samples, reported numeric data on outcomes at follow-up, and examined the transition to psychosis as an outcome. Data extraction adhered to PRISMA guidelines, focusing on baseline pharmacological exposure to antipsychotics, antidepressants, benzodiazepines, and mood stabilizers. A total of 95 studies were analyzed. The majority of studies (96.8 %) explicitly stated whether baseline exposure to antipsychotics was allowed as part of the inclusion criteria. However, actual baseline exposure to antipsychotics was quantified in only 60 % of these studies. Exposure to non-antipsychotic psychoactive therapies was reported in only a fraction of the studies (36.8 % for antidepressants, 16.8 % for benzodiazepines, and 14.7 % for mood stabilizers). In CHR-P longitudinal studies, the meta-analytic proportions of self-disclosed baseline pharmacological exposure ranged from 23.5 % to 24.5 % for antipsychotics, 28.5 % to 30.6 % for antidepressants, 11.2 % to 14.6 % for benzodiazepines, and 5.6 % to 5.9 % for mood stabilizers.

Overall, a non negligible fraction of CHR-P participants is already under psychoactive pharmacological treatment at enrollment. The lack of consistent transparency in this respect may limit the effectiveness of prognostic models. Improved reporting practices are necessary to enhance precision in preventive psychiatry.