We studied the new
catechol-O-methyltransferase inhibitor
tolcapone, 100 and 200 mg, three times daily (tid) in a randomized, double-blind, parallel-group trial involving 202 parkinsonian patients who were experiencing the "wearing-off" phenomenon on
levodopa therapy. After 3 months, patients receiving
tolcapone had a significant decrease in mean daily
levodopa dose requirement compared with placebo-treated patients (p < 0.01). In patients treated with
tolcapone 200 mg tid, daily "off" time, measured using patient diaries, was reduced from baseline by 3.25 hours; this reduction was significantly different from that seen in the placebo group (p < 0.01). Moreover, the number of daily
levodopa intakes was reduced significantly in each
tolcapone group compared with placebo (p < 0.01). We found significant improvements in motor function and overall efficacy in the
tolcapone groups (p < 0.01). The most frequent adverse events were associated with
levodopa treatment.
Dyskinesia developed or worsened in 18% of patients receiving placebo, in 51% receiving
tolcapone 100 mg tid, and in 64% receiving 200 mg tid, with most cases occurring within the first 30 days of the study.
Diarrhea was the most frequent nondopaminergic event, occurring in 14% on placebo, 13% on
tolcapone 100 mg tid, and 19% on 200 mg tid. Overall 18% of patients withdrew because of adverse events: 15% on placebo, 17% on
tolcapone 100 mg tid, and 22% on 200 mg tid. We conclude that
tolcapone as an adjunct offers promise for the relief of the "wearing-off" phenomenon in
levodopa-treated parkinsonian patients.