Amantadine for dyskinesias in Parkinson's disease: a randomized controlled trial

Abstract

Background: Dyskinesias are some of the major motor complications that impair quality of life for patients with Parkinson's disease. The purpose of the present study was to investigate the efficacy of amantadine in Parkinson's disease patients suffering from dyskinesias.

Methods: In this multi-center, double-blind, randomized, placebo-controlled, cross-over trial, 36 patients with Parkinson's disease and dyskinesias were randomized, and 62 interventions, which included amantadine (300 mg/day) or placebo treatment for 27 days, were analyzed. At 15 days after washout, the treatments were crossed over. The primary outcome measure was the changes in the Rush Dyskinesia Rating Scale (RDRS) during each treatment period. The secondary outcome measures were changes in the Unified Parkinson's Disease Rating Scale part IVa (UPDRS-IVa, dyskinesias), part IVb (motor fluctuations), and part III (motor function).

Results: RDRS improved in 64% and 16% of patients treated with amantadine or placebo, respectively, with significant differences between treatments. The adjusted odds-ratio for improvement by amantadine was 6.7 (95% confidence interval, 1.4 to 31.5). UPDRS-IVa was improved to a significantly greater degree in amantadine-treated patients [mean (SD) of 1.83 (1.56)] compared with placebo-treated patients [0.03 (1.51)]. However, there were no significant effects on UPDRS-IVb or III scores.

Conclusions: Results from the present study demonstrated that amantadine exhibited efficacious effects against dyskinesias in 60-70% of patients.

Trial registration: UMIN Clinical Trial Registry UMIN000000780.

Figure 1. Study design and flow diagram.

Top, cross-over scheme of patients randomly allocated to Arms 1 and 2. In Arm 1, amantadine was increased from 100 mg to 300 mg every 7 days, and decreased every 3 days. At 15 days after washout, placebo was administered in a similar manner. In Arm 2, placebo was increased every 7 days and decreased every 3 days, which was followed by a similar washout period and amantadine was then administered in the same fashion. Bottom, flow diagram of patients in the study.

Figure 2. Score changes in RDRS, UPDRS-IVa (dyskinesias), IVb (motor fluctuation), and III (motor disturbance) following amantadine and placebo treatment.

Following amantadine treatment, RDRS scores improved in 64% of participants (−2 points in 27%, and −1 point in 37%), but remained unchanged in 37% of participants. RDRS scores improved in 16% of participants, but did not improve in 84%, following placebo treatment (A). UPDRS-IVa scores significantly improved following amantadine treatment (B). In contrast, UPDRS-IVb and III scores did not improve following treatment with amantadine or placebo (C, D). Data are plotted as scattered diagrams and bars represent means with standard deviations of raw data.