Antipsychotic polypharmacy in Japanese outpatients with schizophrenia: prevalence and sex- and age-related patterns

Antipsychotic polypharmacy (APP), defined as the concurrent use of two or more antipsychotic agents, remains common in clinical practice despite antipsychotic monotherapy being the recommended standard for schizophrenia treatment. This nationwide cross-sectional survey examined the prevalence and determinants of APP among outpatients with schizophrenia in Japan. Data were collected from 3657 patients across 36 medical institutions between 21 and 25 October 2024. Patients were categorized into antipsychotic monotherapy and APP groups, and demographic and clinical characteristics, including age, sex, medication administration frequency, use of long-acting injectables, clozapine, and concomitant psychotropic medications, were compared. Antipsychotic doses were standardized to chlorpromazine equivalents and analyzed by sex and age group. APP was observed in 40.8% of patients. Multivariable analyses showed that APP was significantly associated with male sex, older age, long-acting injectable use, and concomitant use of antiparkinsonian agents, anxiolytics/hypnotics, and mood stabilizers, whereas clozapine use was inversely associated with APP. Chlorpromazine equivalent doses increased with the number of antipsychotics prescribed, peaking in patients aged 40-59 years and declining thereafter. Second-generation antipsychotics predominated overall, although first-generation antipsychotic use increased with polypharmacy. These findings underscore the importance of careful management of APP, taking sex- and age-related prescribing patterns into consideration.