Amantadine

Short-term therapy with amantadine has had beneficial effects on levodopa-induced motor difficulties and dyskinesias in patients with Parkinson's disease. Specifically, dyskinesias decreased by 60 percent in patients taking amantadine; however, its long-term efficacy is unknown. Metman and colleagues conducted a one-year follow-up study to determine the duration of the effect of amantidine in patients with advanced Parkinson's disease.

The original study compared amantadine therapy to placebo in the treatment of patients with levodopa-induced dyskinesias. Thirteen of the original 18 study participants were included in this follow-up (one patient was lost to follow-up and four were assigned to the placebo group). Amantadine and placebo were taken by the participants for one year. These patients had been taking levodopa for treatment of Parkinson's disease for a mean of 12 years. An attempt was made to keep the antiparkinsonian dosage consistent during the one-year follow-up period. Twelve patients continued their regular therapeutic regimen; however, in four patients the dosages were lowered by 25 percent, one patient started treatment with an agonist and three patients were switched to a different dopamine agonist.

Approximately one week before the study started, all of the patients taking amantadine stopped this medication. All of the patients then began taking placebo or a dosage of 100 mg of amantadine three or four times daily (whichever had been their previous standard frequency). Each patient then underwent a motor assessment. This assessment began with participants discontinuing all antiparkinsonian medications six to seven hours before beginning a levodopa infusion (with carbidopa administered orally). A low-protein breakfast was provided, and lunch was withheld until testing was completed. During the last two hours of infusion and after steady-state conditions were achieved, a series of observations (occurring every 10 minutes) of parkinsonian symptoms and choreiform dyskinesias were recorded. The dyskinetic movements were also videotaped and scored by a second neurologist.

In the amantadine group, dyskinesia ratings from the video indicated a reduction of 43 percent compared with the placebo group from the initial acute study. The duration and severity of the dyskinesias and the duration of "off" time were better in the amantadine group than in the placebo group. Conversely, those who received placebo therapy had higher dyskinesia scores than those in the initial placebo group.

The authors conclude that amantadine is associated with a reduction in levodopa-induced motor problems when patients are evaluated one year after amantadine therapy is initiated. This finding underscores the importance of continuing long-term amantadine therapy in patients with levodopa-induced movement disorders and indicates the need for sufficient long-term amantadine therapy before surgery is considered in these patients.

GRACE BROOKE HUFFMAN, M.D.

Metman LV, et al. Amantadine for levodopa-induced dyskinesias. A 1-year follow-up study. Arch Neurol November 1999;56:1383-6.

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