25 Aug Declines and pronounced state-level variation in clozapine use among Medicare patients

Maria Tan

MedicalResearch.com:
Maria Y. Tian, MBS
Department of Medical Education
Geisinger College of Health Sciences
Scranton, Pennsylvania

MedicalResearch.com: What is the background for this study?

Response: Schizophrenia-spectrum disorders are severe, disabling conditions that are associated with substantial economic burden. Approximately one-third of patients have treatment-resistant schizophrenia, which clozapine is the only evidence-based therapy for. Clozapine also provides unique benefits, including reduced suicide risk, aggression, and all-cause mortality. Despite this, it has historically been underutilized due to concerns over adverse effects, required blood monitoring, patient adherence, and limited clinician training. Previous research in Medicaid populations had demonstrated marked state-level variation in use, but little was known about prescribing trends in the U.S. Medicare system, which covers nearly half of individuals with schizophrenia. This study analyzed Medicare Part D data from 2015–2020 to assess national and regional trends in clozapine prescribing and to identify states with significantly different prescribing patterns.

MedicalResearch.com: What are the main findings?

Response: From 2015 to 2020, Medicare clozapine prescriptions per thousand enrollees declined by 18%, and spending decreased by 24.9%, reinforcing prior concerns about underuse. There was persistent geographic variability, averaging a nine-fold difference between the highest and lowest prescribing states each year. We found Massachusetts and South Dakota consistently prescribed significantly more than the national average, while no state prescribed significantly less. Clozapine use was moderately correlated with the percentage of White residents in a state and strongly correlated with Medicaid prescribing patterns.

MedicalResearch.com: Were there any surprising aspects of the results?

Response: A few. Despite clozapine’s status as the only proven treatment for treatment resistant schizophrenia, its use in Medicare patients steadily declined even before the COVID-19 pandemic. Another notable finding was the lack of states prescribing significantly less than average, suggesting that underutilization is a nationwide phenomenon rather than limited to certain regions. Additionally, the strong correlation between Medicaid and Medicare prescribing patterns indicates that shared systemic factors, rather than payer-specific policies, likely drive these trends.

MedicalResearch.com: What should readers take away from your report?

Response: Readers should take away that clozapine prescribing in the Medicare population is low, decreasing, and characterized by large geographic disparities. These patterns are concerning given the medication’s established efficacy and its life-saving potential. Addressing barriers such as clinician education gaps, burdensome monitoring requirements, and racial disparities in prescribing could help align clozapine use with clinical guidelines and improve patient outcomes.

MedicalResearch.com: What recommendations do you have for future research?

Response: Future studies should evaluate prescribing patterns before and after the FDA’s 2025 removal of registry and monitoring requirements and estimate the potential benefits of guideline-based use for treatment resistant schizophrenia. Investigating geographic variation through clinician availability, experience, and attitudes, as well as patient perspectives, could explain regional differences. Comparing clozapine use with other underutilized psychiatric treatments may also reveal broader barriers to optimal care.

MedicalResearch.com: Is there anything else you would like to add?

Response: Improving clozapine utilization could substantially reduce the humanistic and economic burden of treatment resistant schizophrenia. Educational initiatives, such as mandatory training in psychiatric residency, and innovations like point-of-care blood monitoring devices, may help overcome long-standing barriers. Targeted interventions are needed to reduce the large and persistent geographic disparities in clozapine prescribing and to ensure equitable access for all patients who may benefit from this therapy.

Citation

Cavanah LR, Tian MY, et al. Declines and pronounced state-level variation in clozapine use among Medicare patients. PLoS One. 2025;20(8):e032 (13 pages).
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0328495

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Last Updated on August 25, 2025 by Marie Benz MD FAAD