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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.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. |
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