Association of Antipsychotic Polypharmacy vs Monotherapy with Psychiatric Rehospitalization among Adults with Schizophrenia

Abstract

Importance: The effectiveness of antipsychotic polypharmacy in schizophrenia relapse prevention is controversial, and use of multiple agents is generally believed to impair physical well-being. Objective: To study the association of specific antipsychotic combinations with psychiatric rehospitalization. Design, Setting, and Participants: In this nationwide cohort study, the risk of psychiatric rehospitalization was used as a marker for relapse among 62250 patients with schizophrenia during the use of 29 different antipsychotic monotherapy and polypharmacy types between January 1, 1996, and December 31, 2015, in a comprehensive, nationwide cohort in Finland. We conducted analysis of the data from April 24 to June 15, 2018. Rehospitalization risks were investigated by using within-individual analyses to minimize selection bias. Main Outcomes and Measures: Hazard ratio (HR) for psychiatric rehospitalization during use of polypharmacy vs during monotherapy within the same individual. Results: In the total cohort, including 62250 patients, 31257 individuals (50.2%) were men, and the median age was 45.6 (interquartile range, 34.6-57.9) years. The clozapine plus aripiprazole combination was associated with the lowest risk of psychiatric rehospitalization in the total cohort, being superior to clozapine, the monotherapy associated with the best outcomes, with a difference of 14% (HR, 0.86; 95% CI, 0.79-0.94) in the analysis including all polypharmacy periods, and 18% in the conservatively defined polypharmacy analysis excluding periods shorter than 90 days (HR, 0.82; 95% CI, 0.75-0.89; P