entacapone and Substance-Withdrawal-Syndrome

Motor fluctuations associated with levodopa therapy are common problems encountered in the long-term treatment of Parkinson's disease (PD). Entacapone, a peripherally acting, reversible inhibitor of catechol-O-methyltransferase, slows the elimination of levodopa in humans by reducing the formation of 3-O-methyldopa. We conducted a placebo-controlled, double-blind, parallel-group, multicenter trial of entacapone in PD patients with motor fluctuations. Two hundred five patients were randomized to receive either entacapone 200 mg or matching placebo with each dose of levodopa and were followed for 24 weeks. The primary measure of efficacy was the change in percentage of "on" time (relief of parkinsonism) while awake, as recorded by subjects at home in diaries completed at 30-minute intervals. At baseline, patients averaged approximately 10 hours of "on" time per day while awake (60.5% "on" time), and entacapone treatment increased the percent "on" time by 5.0 percentage points. The effect of entacapone was more prominent in patients with a smaller percent "on" time (<55%) at baseline, and increased as the day wore on. Entacapone is effective at increasing the duration of response to levodopa and at relieving parkinsonism in patients experiencing motor fluctuations and was well tolerated during the 24 weeks of treatment.

Topics: Aged; Antiparkinson Agents; Catechols; Double-Blind Method; Dyskinesia, Drug-Induced; Enzyme Inhibitors; Female; Humans; Levodopa; Male; Middle Aged; Movement; Nitriles; Parkinson Disease; Patient Compliance; Substance Withdrawal Syndrome; Treatment Outcome

Forty patients affected by severe Parkinson's disease (PD) were treated with tolcapone as an adjunctive therapy to L-DOPA, for 3-7 months, until this drug was discontinued because of side-effects (2 diarrhoea, one of them with orthostatic hypotension, 2 increments of liver enzymes) or because of mandatory indications of the European drugs authority. All patients, after 3-6 months of L-DOPA therapy adjustments, received entacapone for 3 months again followed by withdrawal. L-DOPA daily dosage was significantly reduced by tolcapone and entacapone (p = 0.01 and 0.05). "On" time was increased by 15% during tolcapone treatment (p < 0.05), and by 8% during entacapone treatment. "Off" time was decreased by 16% during tolcapone and by 7% during entacapone treatment. Entacapone was withdrawn in the same patient who experienced diarrhoea and orthostatic hypotension during tolcapone because of recurrence of side-effects, in 6 patients because of increment of dyskinesias (with hallucinations) and in 1 patients because of rhythmic, jerking myoclonus.

Topics: Aged; Antiparkinson Agents; Benzophenones; Catechols; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Humans; Levodopa; Male; Mental Disorders; Middle Aged; Nitriles; Nitrophenols; Parkinson Disease; Substance Withdrawal Syndrome; Tolcapone