International trends in clozapine utilisation prevalence in adults, adolescents and older people: An observational study in 42 countries between 2015–2024
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Importance Clozapine is the only evidence-based treatment for treatment-resistant schizophrenia (TRS), yet substantial international variation in its use has been reported. Objective To provide a comprehensive and updated assessment of international clozapine utilisation by estimating prevalence across countries using a standardised methodology and examining factors associated with variation in use. Design, Setting, and Participants Repeated cross-sectional study using population-based data from 2015 to 2024. Individual-level data were obtained from 36 countries and 1 special administrative region, supplemented by national clozapine consumption data from 5 additional countries. Analyses were conducted separately for adults (20-64 years; primary analysis), adolescents (10-19 years), and older adults (≥65 years). Main Outcomes and Measures Annual outpatient clozapine utilisation prevalence per 100,000 population by age group, sex, country and calendar year. Associations between clozapine utilisation prevalence and country-level health system, demographic, and socioeconomic indicators were also examined. Results We analysed data from more than 1.1 billion people across all inhabited continents. In 2024, crude adult clozapine use prevalence was highest in Croatia (415.3 per 100,000 population) and Finland (302.0 per 100,000), and lowest in Oman (0.5 per 100,000) and Ethiopia (0.3 per 100,000), representing a 1,384-fold difference. Across most countries, utilisation peaked among individuals aged 50 to 59 years. The male-to-female prevalence ratio ranged from 0.4 in the United Arab Emirates to 2.8 in Colombia. Among adolescents, prevalence was highest in Colombia (42.7 per 100,000) and Croatia (24.4 per 100,000), while among older adults it was highest in Croatia (406.9 per 100,000) and Iceland (339.7 per 100,000). Across all countries, adult clozapine utilisation increased by 17% (95% CI, 16%-18%), from 44.7 per 100,000 population (95% CI, 44.5-44.9) to 52.2 per 100,000 population (95% CI, 51.1-52.4). Country-specific trends ranged from a 71% decrease to a 342% increase. None of the examined indicators explained variation in clozapine utilisation across countries. Conclusion and relevance Clozapine use increased modestly over the past decade but remained highly variable between countries. This variation was not explained by national socioeconomic, healthcare-system, or monitoring-related factors, suggesting an important role for clinical and service-level barriers. The concentration of clozapine use in later adulthood is consistent with delayed initiation and highlights opportunities to improve timely access to evidence-based treatment for TRS. Funding Hsien-Yuan Lane: National Science and Technology Council, Taiwan (NSTC 114-2629-B-039-001-); The China Medical University Hospital Research Project (DMR-113-009 and DMR-114-046). Philippe Mortier: Miguel Servet grant CP21/00078 co–financed by the Instituto de Salud Carlos III (ISCIII) and co–funded by the European Union; grant PI22/00107 funded by ISCIII and co–funded by the European Union; and grant 202220–30–31 from the Fundació la Marató de TV3. Heidi Taipale: Sigrid Jusélius Foundation grant.
Source: medRxiv
Authors: Oliver Scholle, Heidi Taipale, Michael Dörks, Jannik Ohmes, Lise Aagaard, Oleg Aizberg, Salim Al Huseini, Mohamed Alnor, Stojan Bajraktarov, Paolo Bertolini, Robert A. Bittner, Syed Ali Bokhari, Alexandra Bražinová, Dagmar Breznoščáková, Kirsten Catthoor, Marko Čavlina, Andreja Čelofiga, Sherry K. W. Chan, Robert O. Cotes, Adomas Danilevičius, Vlad Dionisie, Uwe Eichler, Zsófia Engi, Rifai Farid, Matthäus Fellinger, Kari Furu, Ary Gadelha, Emily L. Griner, Larus S. Guðmundsson, Daniel Guinart, Katarina Gvozdanović, Yuqi Hu, Fuad N. Ismayilov, Jamila Ismayilova, Sung Woo Joo, Luuk J. Kalverdijk, Mulualem Kelebie, Yuki Kikuchi, Nadzeya Kislaya, Miloslav Kopecek, Francisco T. T. Lai, Hsien-Yuan Lane, Jimmy Lee, Jungsun Lee, Soffy C. López, Jorge E. Machado-Alba, Raffael Massuda, Géric Maura, Claude Mawa, Cristián Mena, Georgios Mikellides, Hassan Mirza, Philippe Mortier, Peter Niemegeers, Prasad S. Nishtala, Tīna Nulle, Uladzimir Pikirenia, Gerald J. Pruckner, Maria Puiu, Julieta Ramirez, Johan Reutfors, Ieva Saliete, Fariza Sani, Catharina C.M. Schuiling-Veninga, Dan Siskind, Lina Škiudaitė, Samvel Sukiasyan, Charmaine Tang, Karine Tataryan, David Taylor, Antonio Teixeira Rodrigues, Hiroaki Tomita, Carla Torre, Mike Trott, Fuu-Jen Tsai, Hélène Verdoux, Yahyah Wehbe, Ebenezer Oloyede, Christian J. Bachmann
Institutions: Leibniz Institute for Prevention Research and Epidemiology - BIPS, University of Eastern Finland, Niuvanniemi Hospital, Region Stockholm, Stockholm Municipality, Karolinska Institutet, Carl von Ossietzky Universität Oldenburg, University of Southern Denmark, Belarusian State Medical University, Ministry of Health, Ss. Cyril and Methodius University in Skopje, Goethe University Frankfurt, Max Planck Society, Ernst Strüngmann Institute for Neuroscience, University Hospital Frankfurt, Comenius University Bratislava, University of Pavol Jozef Šafárik, University of Antwerp, Ziekenhuis aan de Stroom, Hrvatski zavod za javno zdravstvo, University of Maribor, University Clinical Centre Maribor, University of Hong Kong, Emory University, Ministry of Health of the Republic of Lithuania, Carol Davila University of Medicine and Pharmacy, Wissenschaftliches Institut der AOK, University of Szeged, Raja Isteri Pengiran Anak Saleha Hospital, Klinik Hietzing, Norwegian Institute of Public Health, Universidade Federal de São Paulo, University of Iceland, Hofstra University, Centro de Investigación Biomédica en Red de Salud Mental, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, Hospital Del Mar, Hospital del Mar Research Institute, Andrija Stampar Teaching Institute of Public Health, Azerbaijan Medical University, Asan Medical Center, University of Ulsan, University Medical Center Groningen, University of Groningen, University of Gondar, Tohoku University, Charles University, National Institute of Mental Health, Asia University, China Medical University, China Medical University Hospital, Nanyang Technological University, Institute of Mental Health, Universidad Tecnológica de Pereira, Universidade Federal do Paraná, l'Assurance Maladie, State University of Applied Sciences in Elbląg, Finis Terrae University, University of Nicosia, Sultan Qaboos University Hospital, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, University of Bath, Johannes Kepler University of Linz, Hospital Borda, Riga Stradiņš University, The University of Queensland, Metro South Health, Queensland Centre for Mental Health Research, Armenian State Pedagogical University after Khachatur Abovian, Yerevan State Medical University, King's College London, South London and Maudsley NHS Foundation Trust, University of Minho, University of Lisbon, Université de Bordeaux, Inserm, Bordeaux Population Health, University of Oxford, University Hospital Ulm
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: Novartis Pharma
OpenAlex ID: W7213754889