Physician Experiences With and Perspectives on Clozapine Prescribing
Authors: Ameet Sarpatwari, Zhigang Lu, Massimiliano Russo, Heidi Zakoul, Su Been Lee, Gita A. Toyserkani, Esther H. Zhou, Cynthia LaCivita, Katherine Hyatt Hawkins Shaw, Gerald J. Dal Pan, Aaron S. Kesselheim
Journal: JAMA Network Open (2025)

Importance Clozapine is an effective medication for treatment-resistant schizophrenia but can cause agranulocytosis. Since its approval, patients taking clozapine have been required to undergo regular blood testing to screen for neutropenia. In 2015, the risk management programs were merged into a single risk evaluation and mitigation strategy (REMS), which mandates that prescribers undergo a certification process in which they attest to understanding the risk of agranulocytosis and commit to performing required blood testing. It is unknown how the clozapine REMS program has affected clinical practice. Objective To understand physicians’ perceptions of and experiences with the clozapine REMS program. Design, Setting, and Participants This survey study included US physicians who prescribed clozapine in 2021 or 2022. A 57-question, closed-field questionnaire was administered via paper or online. The first survey wave took place from May to October 2022 and the second from October 2022 to January 2023. Exposures Gender, race and ethnicity, practice specialty, practice setting, practice region, professional time in clinical practice, years since graduation from medical school, and number of patients prescribed clozapine in the past 3 years. Main Outcomes and Measures Experiences with and perceptions of the REMS certification process, patient initiation, and the REMS safe use requirements were measured using Likert scales. Descriptive statistics and multivariable modeling were used to analyze the study results. Results Of 750 physicians contacted, 196 responded (30% response rate). Most respondents were male (129 [67%]), most identified as Asian (48 [25%]) or White (124 [63%]), and most were psychiatrists (165 [86%]); almost half (88 [45%]) practiced in an outpatient group setting. Most respondents reported that the information provided during certification was clear (179 [92%]) and contained useful drug information (145 [75%]) and that the paperwork associated with required blood testing facilitated physician-patient conversation (102 [53%]). Most respondents wanted certification materials to include all clinically important risks (172 [89%]) and benefits (139 [72%]) and reported frequent delays in medication access owing to required blood testing (115 [60%]). Two-thirds of respondents agreed that the positives of the certification process (123 [64%]) and blood testing requirements (129 [68%]) outweighed the negatives. In multivariable analysis, negative REMS perceptions were less common among physicians in practice longer (≥35 vs &amp;amp;lt;15 years since medical school: odds ratio [OR], 0.28; 95% CI, 0.10-0.80) and among American Indian or Alaska Native, Black, and Native Hawaiian or Other Pacific Islander physicians compared with White physicians (OR, 0.08; 95% CI, 0.01-0.73). Conclusions and Relevance In this survey study of physician prescribers of clozapine, a majority were satisfied with the clozapine REMS program but highlighted the need for enhanced educational materials and administrative efficiency.