Tolcapone improves motor function in parkinsonian patients with the "wearing-off" phenomenon: a double-blind, placebo-controlled, multicenter trial.

Abstract

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.

• Authors: A H Rajput, W Martin, M H Saint-Hilaire, E Dorflinger, S Pedder
• Journal: Neurology (Neurology) Vol. 50 Issue 5 Suppl 5 Pg. S54-9 (May 1998) ISSN: 0028-3878 [Print] United States
• PMID: 9591523 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antiparkinson Agents
• Benzophenones
• Catechol O-Methyltransferase Inhibitors
• Dopamine Agents
• Enzyme Inhibitors
• Nitrophenols
• Levodopa
• Tolcapone

Topics

• Aged
• Antiparkinson Agents (adverse effects, pharmacology)
• Benzophenones (adverse effects, pharmacology)
• Canada
• Catechol O-Methyltransferase Inhibitors
• Dopamine Agents (pharmacokinetics)
• Double-Blind Method
• Enzyme Inhibitors (adverse effects, pharmacology)
• Female
• Humans
• Levodopa (pharmacokinetics)
• Male
• Middle Aged
• Nitrophenols
• Parkinson Disease (drug therapy, enzymology, physiopathology)
• Psychomotor Performance (drug effects)
• Tolcapone
• United States