Real-world effectiveness of antipsychotic polytherapy on rehospitalization in psychotic disorders: A French nationwide cohort analysis.

Abstract

Background: Antipsychotic polytherapy (APP) is common in clinical practice for psychotic disorders. Previous studies suggest that APP may offer advantages over monotherapy (APM) regarding effectiveness and all-cause discontinuation. This nationwide study assessed the reproducibility and robustness of these findings. The primary objective was to compare psychiatric readmission rates between APP and APM in psychotic disorder patients METHODS: Data were extracted from the French National Health insurance database (SNDS). Patients aged 18 or older with at least one psychiatric hospitalization between 1 January 2014 and 31 December 2020 were included. The primary outcome was time to psychiatric readmission. A within-individual study design was applied to limit confounding, by comparing periods with different treatment exposures within the same patient FINDINGS: A total of 234,959 adults with at least one hospitalization for a psychotic condition were included, with a median follow-up of 7 years. Antipsychotic treatment was associated with a (20%-50%) reduction in psychiatric readmission risk compared with no treatment. Rehospitalization remained common (71.6%). The median cumulative rehospitalization duration was 67 days, and 21.8% of patients had more than four admissions. Among the 71.1% exposed to APP, several combinations demonstrated distinct benefits. Clozapine-inclusive combinations (with risperidone or amisulpride) and loxapine-amisulpride combinations reduced rehospitalization risk. Quetiapine combinations also lowered risk by (10%- 20%) compared with quetiapine monotherapy INTERPRETATION: Derived from a large cohort, our findings corroborate previous evidence that APP's benefit reduces psychiatric rehospitalization and support its utility for psychotic specific patient subpopulations. This study confirms the reproducibility and robustness of APP's effectiveness in real-world settings.