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Study Identifies Barriers and Facilitators to Use of Clozapine for Treatment-Resistant Veterans with Schizophrenia

Clozapine is the only medication proven effective for treatment-resistant schizophrenia, but less than 25% of treatment-resistant patients with this disabling disorder receive clozapine in most settings. Clozapine is associated with side effects that include agranulocytosis, significant weight gain, diabetes, and myocarditis, and, thus, requires frequent monitoring and reporting. This study sought to identify facilitators and barriers to clozapine use – and to inform the development of interventions to maximize appropriate use. Using FY2013 VA prescribing data, facility-level clozapine utilization rates were calculated for Veterans with schizophrenia or schizoaffective disorder receiving clozapine at each VA facility. Between September 2014 and May 2015, 70 semi-structured phone interviews were conducted with key informants (e.g., mental health leadership, psychiatrists, clinical pharmacists, dispensing pharmacists, advanced practice nurses) from five high- and five low-utilization VAMCs from different US regions, including urban and rural settings. Interview questions focused on: perceptions of clozapine risks and benefits, local and national clozapine policies and processes (formal and informal), departmental interfaces regarding clozapine use, sources of clozapine policies and procedures, and clinicians' impressions of patient perceptions of clozapine.


  • Factors associated with high utilization of clozapine for Veterans with schizophrenia included: providing access to transportation for Veterans; having sufficient capacity to enroll patients; use of multi-disciplinary teams, including non-physician providers; better coordination of care through mental health intensive case management (MHICM) or clozapine clinics; and creation of systems to reduce reliance on too few individuals.
  • Factors associated with low utilization of clozapine included lack of champions to support clozapine processes and limited-capacity care systems.
  • Barriers identified at both high- and low-utilization facilities included time-consuming paperwork, reliance on few individuals to facilitate processes, and issues related to transportation for Veterans living far from VA care facilities.


  • Implementation efforts to organize, streamline, and simplify clozapine processes, development of a multidisciplinary clozapine clinic, increasing the size and capacity of existing clinics, and provision of transportation are reasonable targets to increase clozapine utilization.


  • What was deemed high-utilization of clozapine in this study may not reflect optimal utilization, as the optimal rate has not been defined.

All authors are part of HSR&D's Center for Healthcare Organization and Implementation Research (CHOIR). The study was funded by locally-initiated project grants from CHOIR and Mental Health-QUERI.

PubMed Logo Gören J, Rose A, Engle R, et al. Organizational Characteristics of High- and Low-Clozapine-Utilization Clinics in the Veterans Health Administration. Psychiatric Services. June 15, 2016;e-pub ahead of print.

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What are HSR Publication Briefs?

HSR requires notification by HSR-funded investigators about all articles accepted for publication. These journal articles are reviewed by HSR and publication briefs or summaries are written for a select number of articles that are then forwarded to VHA Central Office leadership to keep them informed about important findings or information. Articles to be summarized are selected by HSR based on timeliness of the findings, interest of leadership, or potential impact on the organization. Publication briefs are written for only a small number of HSR published articles. Visit the HSR citations database for a complete listing of HSR articles and presentations.

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