Introduction. Schizophrenia-spectrum disorders are debilitating and contribute to a substantial economic burden. Clinicians have historically underutilized clozapine, an atypical antipsychotic traditionally reserved for use in treatment-resistant schizophrenia, due to the medication`s adverse effect profile and associated management requirements, concerns of poor treatment adherence, and poor training/exposure to the use. In addition to alleviating schizophrenia symptoms when multiple other medications have failed, clozapine has other unique benefits that compel its use such as its use being associated with reduced suicide ideation and action, aggression, substance use, and all-cause mortality. Methods. This study aimed to characterize clozapine utilization by US Medicare patients from 2015-20. Additionally, we identified the states that prescribed significantly different amounts than the national average. Results. We observed a steady decrease in clozapine use adjusted for population (-18.0%) and spending (-24.9%) over time. For all years, there was significant geographic heterogeneity (average: nine-fold) in population-corrected clozapine use. Massachusetts (2015-20: 95.4, 82.7, 76.8, 72.2, 71.2, 63.7 prescriptions per thousand enrollees) and South Dakota (2015-20: 78.0, 77.4, 78.4, 75.6, 72.0, 71.6) were the only states that prescribed significantly more than average, and none prescribed significantly less. Discussion. Clozapine use by US Medicare patients is low, decreasing, and concerning for underutilization, patterns likewise seen for the US Medicaid recipients. Further study of the reasons for the state variation is needed. Education interventions, training reform, and devices that ease required routine blood monitoring are all practical solutions to optimize clozapine use.

BJP`s research is supported by the Pennsylvania Academic Clinical Research Center (001, 004) and the Health Resources and Services Administration (D34HP31025). Maria Tian is supported by the Pennsylvania Academic Clinical Research Center (004). Prior (2019 to 2021) osteoarthritis research was supported by Pfizer and Eli Lilly. The other authors have no disclosures.

BJP was supported by HRSA (D34HP31025). NIEHS (T32- ES007060-31A1) provided the software for this research.

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