Trimetazidine and parkinsonism: A prospective study

Background: Although trimetazidine may induce parkinsonian symptoms in some patients, no systematic characterization has been reported on parkinsonism occurring during trimetazidine treatment since the first case reports.

Objective: To systematically investigate parkinsonism occurring during trimetazidine use.

Methods: Thirty-three consecutive patients on trimetazidine treatment with previously unrecognized parkinsonian symptoms were enrolled. Detailed neurological and neuropsychological examinations were performed at baseline and 1 and 12 months after trimetazidine withdrawal. In cases with persisting parkinsonian symptoms and suspected de novo Parkinson's disease, antiparkinsonian treatment was initiated. Twenty of the 33 patients underwent DaTSCAN imaging.

Results: After trimetazidine withdrawal, parkinsonism was completely resolved in 11 cases. The comparison of baseline data of patients with reversible and persisting parkinsonism showed that trimetazidine-induced reversible parkinsonism was mainly characterized by akinesia, rigidity, postural instability and gait disturbances (PIGD; PIGD scores: 5.3 ± 3.8 vs. 2.0 ± 1.6 points, p = 0.006) rather than tremors (tremor scores: 1.5 ± 2.2 vs. 7.7 ± 4.6 points, p = 0.000). Trimetazidine-induced reversible parkinsonism was also more symmetrical (asymmetry index: 3.1 ± 3.6 vs. 40.1 ± 22.2, p = 0.000) and milder in severity (MDS-UPDRS Part III. scores: 10.5 ± 19. vs. 30.5 ± 11.3, p = 0.040) than nonreversible parkinsonism. DaTSCAN images were normal in all trimetazidine-induced reversible parkinsonism patients, while these images were abnormal in every patient with nonreversible parkinsonism. In cases of nonreversible parkinsonism, preexisting, incipient Parkinson's disease was suspected by clinical appearance and a good response to antiparkinsonian medication.

Conclusions: Mild and symmetrical appearance of parkinsonism with normal DaTSCAN results can indicate drug-induced parkinsonism. Trimetazidine discontinuation generally results in permanent remission in such cases.