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.