Clozapine-induced Myocarditis in Korea: Analysis of a Nationwide Database and Comparison to Other Countries.

Objective: Clozapine, though the mainstay treatment for treatment-resistant schizophrenia, is associated with potentially fatal adverse reactions, including myocarditis. The incidence of clozapine-induced myocarditis (CIM) demonstrates geographic and ethnic variability; however, reports from Asia remain scarce. This study aimed to provide a comprehensive overview of CIM in Korea and compare findings with reports from other countries. Methods: CIM cases were identified from Korean National Health Insurance Service (NHIS) database based on diagnostic codes, prescription timelines, and clinical details. Patient characteristics and concomitant medications were analyzed. A PubMed search using a validated query was conducted to compare CIM in Korea with those reported in other regions. Results: From the NHIS database of 36,286 patients with schizophrenia spectrum disorders who were prescribed clozapine, 29 patients (0.08%) received myocarditis diagnosis. Among them, 9 patients (0.02%) who discontinued clozapine after the diagnosis could be considered probable CIM. Among these probable CIM cases, 4 male patients (0.01%) developed myocarditis within 30 days of clozapine initiation, while 5 patients developed myocarditis during the maintenance period. Two patients were found to have died from CIM. The literature review yielded 38 relevant articles on CIM incidence, including 4 from Asia, 4 from Europe, 3 from the Americas, 16 from Australia, and 4 from New Zealand. A comparison between countries demonstrated a lower incidence of CIM in Korea. Conclusion: Consistent with the previous report, the incidence of CIM in Korea was less than 0.1%, which is lower than the incidences in other countries.