Clozapine prescribing in Germany: temporal trends and regional variations, 2012 to 2022

Clozapine is the most effective and only approved drug in treatment-resistant schizophrenia (TRS). Studies based on data up to 2014 concluded that it is underutilized in most industrialized countries, including Germany. Since 2019, national guidelines explicitly recommend clozapine as first-line therapy in TRS. We aimed to assess whether clozapine use in Germany has increased in recent years and to examine regional variations. Using claims data covering about 20% of the German population (GePaRD), we calculated the yearly prescription prevalence and incidence of clozapine among individuals aged 0-64 years based on outpatient dispensations. For 2022, we also assessed regional variations in clozapine prescription prevalence at the district level (restricted to N=202 districts with [≥]20,000 individuals). From 2012 to 2022, the overall (age- and sex-standardized) prescription prevalence of clozapine continuously decreased by 16% (from 77.6 to 65.5 per 100,000). The relative decline was greatest in women aged 30-39 years (-51%) and in men aged 30-34 years (-57%), in urban areas (large urban cities: -23%; urban districts: -16%), and in regions with high socioeconomic status (-22%). Over the same period, the overall prescription incidence of clozapine decreased by 41%. In 2022, regional clozapine prescription prevalence differed up to 39-fold. In conclusion, clozapine prescribing in Germany did not increase from 2012 to 2022, despite new clozapine-favoring guidelines, and showed substantial regional variation. Our results suggest a persisting underutilization of clozapine in most regions in Germany. Further research on barriers and facilitators on clozapine use in Germany is needed.