title: 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.affiliation: Division of Neurology, Royal University Hospital, Saskatoon, Saskatchewan, Canada.
authors.forename: A H
authors.initials: AH
authors.lastname: Rajput
authors.forename: W
authors.initials: W
authors.lastname: Martin
authors.forename: M H
authors.initials: MH
authors.lastname: Saint-Hilaire
authors.forename: E
authors.initials: E
authors.lastname: Dorflinger
authors.forename: S
authors.initials: S
authors.lastname: Pedder
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000494:pharmacology*; D001577:Benzophenones / Q000009:adverse effects / Q000494:pharmacology*; D002170:Canada; D065098:Catechol O-Methyltransferase Inhibitors; D015259:Dopamine Agents / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009596:Nitrophenols; D010300:Parkinson Disease / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000187:drug effects*; D000077867:Tolcapone; D014481:United States
chemical_list: D000978:Antiparkinson Agents; D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D009596:Nitrophenols; D007980:Levodopa; D000077867:Tolcapone