Global trends in clozapine utilisation between 2014 and 2024: a longitudinal epidemiological study with data from 75 countries

Background: Clozapine underutilisation in treatment-resistant schizophrenia represents a global public health challenge. We aimed to investigate contemporary trends of clozapine utilisation internationally. Methods: National estimates of clozapine utilisation were obtained for 75 countries through analysis of national prescribing databases and global pharmaceutical sales data from the IQVIA Multinational Integrated Data Analysis System. The annual national prevalence of clozapine utilisation was calculated between 2014 and 2024 via the number of defined daily doses (DDD) utilised per 1000 inhabitants per day (DDD/1000 inhabitants/day). Time trends in the annual prevalence of utilisation were tested using linear regression. Haematological monitoring stringency and the number of psychiatrists were explored as predictors of clozapine utilisation. Findings: In 2024, the global average clozapine utilisation was estimated as 0.46 DDD/1000 inhabitants/day, being greatest in New Zealand (2.99 DDD/1000 inhabitants/day), and Finland (2.61 DDD/1000 inhabitants/day) and lowest in Singapore (0.0007 DDD/1000 inhabitants/day). Over the period analysed, worldwide clozapine use increased by 0.13 DDD/1000 inhabitants/day. In 45 (60.0%) countries clozapine utilisation increased significantly, in 19 (25.3%) use remained similar, but in 11 (14.7%) use decreased significantly. Higher clozapine utilisation was associated with a higher number of psychiatrists (B = 0.11 [95% CI 0.05, 0.17]), but was unrelated to haematological monitoring stringency (B = 0.007 [95% CI -0.02, 0.03]). Interpretation: Whilst global utilisation appears increasing, substantial intercountry variation in clozapine use continues. The absence of an association between haematological monitoring stringency and rate of clozapine utilisation suggests the need for measures beyond monitoring relaxation within policy and practice to systematically increase use. Funding: Provided by St Patrick's Mental Health Services.