Metabolic syndrome in stable long-term antipsychotic monotherapy and polypharmacy among patients with schizophrenia: a real-world comparative study.

Abstract

Background: Metabolic syndrome is a major contributor to premature cardiovascular morbidity and mortality among people with schizophrenia. Antipsychotic polypharmacy is common, but its independent metabolic burden remains uncertain.

Objective: To compare metabolic syndrome in patients receiving stable long-term antipsychotic monotherapy or polypharmacy and to examine high metabolic-risk exposure, chlorpromazine-equivalent dose, and long-acting injectable (LAI) use.

Methods: This retrospective study included 370 adults with schizophrenia spectrum disorders receiving an unchanged antipsychotic regimen for at least five years at a community mental health center. Patients received monotherapy (n=144) or polypharmacy (n=226). Metabolic syndrome was defined using International Diabetes Federation criteria. Antipsychotic dose was standardized to chlorpromazine equivalents, and multivariable logistic regression was used.

Results: Metabolic syndrome was present in 143 patients (38.6%) and was numerically more frequent with polypharmacy than monotherapy (41.2% vs. 34.7%, p=0.216). LAI use (67.3% vs. 37.5%, p<0.001) and median chlorpromazine-equivalent dose (1010.0 vs. 454.5 mg/day, p<0.001) were higher with polypharmacy. However, neither LAI use (adjusted OR = 1.220, 95% CI 0.767-1.941, p=0.401) nor chlorpromazine-equivalent dose per 100 mg/day (adjusted OR = 1.003, 95% CI 0.954-1.055, p=0.899) was independently associated with metabolic syndrome. Current smoking remained associated with metabolic syndrome (adjusted OR = 1.996, 95% CI 1.251-3.185, p=0.004).

Conclusions: In this selected cohort with stable long-term treatment, polypharmacy was associated with greater dose and LAI exposure, but independent associations of treatment modality, current dose, LAI use, or olanzapine/clozapine exposure with metabolic syndrome were not detected. Comprehensive cardiometabolic monitoring and smoking cessation remain priorities.