Amantadine as Treatment for Levodopa-Induced Dyskinesia

ABSTRACT

BACKGROUND: Dyskinesia is a common side effect complicating long-term levodopa therapy for Parkinson's disease. However, the pathogenesis of dyskinesia has not been completely understood. In recent animal studies, it has been reported that a NMDA (N-methyl-D-aspartate) antagonist reduced levodopa-induced dyskinesia. These findings suggest that the hyperfunction of NMDA receptors on striatal efferent neurons contributed to the pathogenesis of dyskinesia. Amantadine has also been recently shown to antagonize central NMDA receptors. In the present study, we observed amantadine efficacy in levodopa-induced dyskinesia in parkinsonian patients. METHODS:Twenty-two parkinsonian patients with levodopa-induced dyskinesia participated in a placebo-controlled, cross-over study. We prescribed 100 mg amantadine daily as a starting dose, which was built up every four days and titrated up to 400 mg a day. After two weeks of a wash-out period, a placebo was given with the same schedule. The doses of levodopa and other antiparkinsonian drugs were unchanged during this period. We assessed the duration and disability of dyskinesia (UPDRS part IV, item 32 and 33) based on diary and interview. RESULTS: Amantadine was superior to placebo in reducing the duration of dyskinesia in 9 patients (42.9%) and the disability of dyskinesia in 11 patients (52.4%). The reduction of the duration and disability of dyskinesia was correlated with the dose of amantadine. CONCLUSIONS These findings suggest that amantadine can improve levodopa induced dyskinesia and supports the view that the hyperfunction of NMDA receptors contributes to the pathogenesis of levodopa induced dyskinesia.