Trimetazidine use in Parkinson's disease: Is it a resolved problem?

Trimetazidine, an antianginal drug, can worsen the symptoms of movement disorders, therefore, the European Medicines Agency (EMA) recommended avoiding the use of this drug in Parkinson's disease (PD). We investigated the impact of this recommendation on the observed trend of trimetazidine use in PD in Hungary from 2010 to 2016 by conducting a nationwide, retrospective study of health administrative data of human subjects. Interrupted time series analyses were performed to explore changes in user trends after the EMA recommendations. We found that trimetazidine use in PD decreased by 6.56% in each 6-month interval after the EMA intervention (a change in trend of -530.22, 95% CI = -645.00 to -415.44, p< 0.001 and a decrease in level of -567.26, 95% CI = -910.99 to -223.53, p = 0.005 12 months postintervention). Trimetazidine discontinuation was the highest immediately after the intervention, however, its rate slowed down subsequently (a change in trend of -49.69, 95% CI = -85.14 to -14.24, p = 0.11 without significant level effects). The rate of new trimetazidine prescriptions did not reduce significantly, therefore, the decreased overall use was mainly attributable to the increased rate of discontinuation only. The main indications for trimetazidine use were circulatory system disorders, especially angina pectoris, however, off-label utilization was also considerable (40%). The EMA recommendations on trimetazidine use seem to be only moderately effective in Hungary. Although the number of patients with PD on the drug modestly decreased after the EMA restrictions, trimetazidine is still widely used in PD for both on- and off-label indications.SIGNIFICANCE STATEMENTTrimetazidine can worsen the symptoms of movement disorders in a clinically relevant manner and its use is consequently not recommended in Parkinson's disease (PD) by the European Medicines Agency (EMA). The impact of the EMA recommendations on trimetazidine use in PD has not yet been evaluated, therefore, we conducted a nationwide, retrospective study to address this question in Hungary. According to our results, the restrictions on trimetazidine use are only moderately effective. Although the number of patients with PD on the drug modestly decreased after the EMA recommendations, trimetazidine is still widely used in PD for both on- and off-label indications. Our findings promote another safety communication to resolve a clinically important problem and to improve the management of patients with PD.