Placebo-controlled trial of amantadine in multiple-system atrophy

Multiple-system atrophy (MSA) often presents as atypical parkinsonian syndrome with rapid progression and poor response to levodopa. Reports on the open-label use of amantadine in MSA suggest variable antiparkinsonian efficacy. The authors therefore conducted a double-blind, placebo-controlled crossover trial of amantadine in MSA patients.

Eight patients were enrolled in this study. They received either amantadine 200 mg twice daily or placebo for 3 weeks, followed by a 1-week washout and the alternate treatment of 3 weeks. Antiparkinsonian effects were evaluated using the Unified Parkinson's Disease Rating Scale part II (UPDRS-II, activities of daily living) and UPDRS-III (motor examination) before and at the end of each treatment phase. Timed tests were also performed according to the CAPIT protocol.

There was a trend toward reduction of UPDRS-III scores during amantadine treatment (P = 0.058). Delta values of the treatment arm were higher than those of the placebo arm. However, this difference (-2.25 pt; 95% CI, -6.7-2.2) failed to reach significance. Reduction of UPDRS-III subscores for akinesia, rigidity, tremor, postural instability, and gait disorder failed to reach significance too. The hand-arm movement test revealed nonsignificant improvement in the amantadine arm.

This study suggests that amantadine fails to provide clinically significant antiparkinsonian benefit to patients with MSA. The authors cannot exclude mild effects due to the limited sample size.