【Objective】Clozapine (CLZ) is an essential drug for the management of treatment-resistant schizophrenia and was approved in Japan in 2009. Previous studies reported the underuse of CLZ and regional disparities in its use in Japan. We aimed to elucidate the clinical epidemiology and real-world use of CLZ in Japan using National Database of Health Insurance Claims and Specific Health Checkups (NDB) Open Data.
 【Methods】The NDB covers more than 95% of all administrative claims data from the national health insurance system in Japan. The Ministry of Health, Labour and Welfare provides an open-access version of the NDB (NDB Open Data) covering fiscal year (FY) 2014 to FY2018. The data include the total number of CLZ prescriptions for inpatients and the total number of service fees for management of both inpatients and outpatients using CLZ stratified by Japan's 47 prefectures, age, and sex. We estimated the number of patients using CLZ based on the number of service fees for patient management.
 【Results】The annual number of 100-mg CLZ tablets prescribed to inpatients in Japan increased from 0.8 million in FY2015 to 1.7 million in FY2018. In FY2018, data on 25-mg CLZ tablets were also available, and CLZ prescriptions totaled 155 mg per 1,000 population. The estimated number of patients using CLZ increased from 1,330 in FY2014 to 3,254 in FY2018. Outpatients accounted for 50.3% in FY2014 and 55.3% in FY2018. In terms of regional disparities, Okinawa prefecture had the largest number of CLZ prescriptions (6,290 mg per 1,000 population) and Shimane prefecture had the smallest (350 mg per 1,000 population). Miyazaki prefecture had an estimated 13.4 patients using CLZ per 100,000 population versus 0.64 in Saitama prefecture. Based on data from the Clozaril Patient Monitoring Service, in FY2018 the estimated number of patients using CLZ per hospital was 14.1 in Okayama prefecture and 0.75 in Shimane prefecture. By sex, the estimated number of patients using CLZ per 100,000 population in FY2018 was 2.8 among men and 2.4 among women. In both sexes, the age group with the largest number of patients using CLZ was 35 to 39 years (7.2 and 6.6 per 100,000 population among men and women, respectively). The average CLZ dose in inpatients was 387 mg in men and 348 mg in women.
 【Discussion】As NDB Open Data summarizes administrative claims data, there are several limitations. However, these data can be used to capture real-world use of CLZ nationwide. This study revealed the clinical epidemiology and regional disparities of CLZ use in Japan. Although the number of patients using CLZ has been increasing, this number is considerably smaller in Japan than in other countries due to delayed approval and strict regulations.
 Authors' abstract