Frequency of anticholinergic drug use in patients treated with aripiprazole once-monthly: a 2-year cohort study using European healthcare databases

Background: Extrapyramidal symptoms (EPS) in association with the long-acting, injectable, atypical antipsychotic aripiprazole once monthly (AOM) have been observed in clinical trials, but information on EPS requiring treatment with anticholinergic drugs in clinical practice is limited. Objectives: The objective of this European post-authorisation safety study (PASS) was to assess the risk of EPS-related events, as defined by dispensings of anticholinergic drugs, linked to the use of AOM in routine clinical practice. Design: This European cohort study was based on healthcare databases from Germany (German Pharmacoepidemiological Research Database GePaRD), Italy (Caserta and Palermo healthcare claims databases), and Sweden (National health registers). New users of AOM were followed from their first dispensing for a maximum of 2 years. Methods: Primary study outcome was an EPS-related event, defined as the first dispensing of an anticholinergic drug. The crude incidence rate (IR) and the cumulative incidence of EPS-related events were estimated. Cox proportional hazard regression modelling was performed to further investigate the effect of potential risk factors for the occurrence of EPS-related events. Results: A total of N = 1748 patients were eligible for inclusion into the primary study populations (Germany N = 629; Italy N = 519; Sweden N = 600). IRs of EPS-related events per 100 patient years were highest in Italy (IR = 18.4; 95% confidence interval (CI) 15.3–22.1), followed by Sweden (IR = 7.7; 95% CI 5.8–10.2) and Germany (IR = 3.4; 95% CI 2.4–4.6). Rates were highest during the first 30 days after treatment initiation. Cumulative incidences after 2 years of treatment were 27.8% (Italy), 11.5% (Sweden), and 10.0% (Germany). Diabetes and previous antipsychotic drug use were identified as risk factors for EPS-related events. Conclusion: In this observational study, incidence rates of EPS-related events, defined as the first dispensing of an anticholinergic drug during follow-up, were compatible with the known safety profile of AOM but showed substantial regional variation. Trial registration: EU PAS number EUPAS21056.