Trimetazidine Use in Parkinson's Disease: Is It a Resolved Problem?

Abstract

Trimetazidine (TMZ), 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 TMZ 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 TMZ use in PD decreased by 6.56% in each six-month interval after the EMA intervention [a change in trend of -530.22, 95% confidence interval (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]. TMZ 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 TMZ prescriptions did not reduce significantly, therefore, the decreased overall use was mainly attributable to the increased rate of discontinuation only. The main indications for TMZ use were circulatory system disorders, especially angina pectoris, however, off-label utilization was also considerable (40%). The EMA recommendations on TMZ 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, TMZ is still widely used in PD for both on-label and off-label indications.

Keywords: European Medicines Agency; Parkinson’s disease; angina pectoris; interrupted time series analysis; trimetazidine.

Figure 1.

Patients having Parkinson’s disease with ongoing trimetazidine treatment (A), new initiations or withdrawal (B) from 2010 to 2016 and interrupted time series models. EMA, European Medicines Agency; PD, Parkinson’s disease; TMZ, trimetazidine.

Figure 2.

Possible indications for ongoing TMZ treatment (A) and new initiations on the drug (B) in PD from 2010 to 2016. The following categorizations were used: (1) antianginal indication (ICD-10-CM I20, on-label prescriptions); (2) other cardiological indications (ICD-10-CM I00-I99 with the exemption of ICD-10-CM I20, possibly off-label prescriptions after the EMA warning); (3) ophthalmological indications (ICD-10-CM H30-H36, definitely off-label prescriptions after the EMA warning); and (4) otological indications (ICD-10-CM H80-H83, definitely off-label indications after the EMA warning). Other non-investigated disorders might have also served as the basis of TMZ use or initiation. One patient might have had more than one diagnosis. ICD-10-CM, International Classification of WHO Diseases, 10th Revision, Clinical Modification.