Long‐term evaluation of amantadine and levodopa combination in parkinsonism by double‐blind crossover analyses

Twenty-three patients with Parkinson's disease participated in long-term, double-blind evaluations of the effectiveness and side effects of amantadine in combination with levodopa therapy. Sixteen patients completed the year-long study, which consisted of randomized crossover of amantadine and placebo before levodopa was begun and again after 5 and 11 months of continuous levodopa therapy. Initially, 16 of 23 patients (70 percent) had a favorable response to amantadine during the first crossover period. After 1 year of levodopa, at least eight of 16 patients (50 percent) responded favorably to amantadine compared with placebo. Some of the amantadine responders previously had been nonresponders, and vice versa. The response to amantadine was quantitatively similar in the responders even after the patients had been receiving levodopa therapy. Amantadine should be tried as a therapeutic agent in addition to levodopa for parkinsonism if more beneficial effect is desired, even if amantadine was previously ineffective in the same patient.