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PARIS, June 9 -- Adding entacapone (Comtan) to levodopa early in Parkinson's disease does not delay onset of dyskinesias, researchers said here. Action Points Instead, and contrary to expectations, early entacapone hastened onset of dyskinesias, lead author C. Warren Olanow, M.D., of Mount Sinai School of Medicine in New York, told attendees at the International Congress of Parkinson's Disease and Movement Disorders. Dyskinesias develop in most Parkinson's patients after five to 10 years of successful therapy with levodopa. Evidence indicates they may be caused by pulsatile dopaminergic stimulation, Dr. Olanow said, rather than the normal continuous stimulation produced by the healthy brain. There's some evidence, he said, that minimizing pulsatile stimulation may delay the onset of dyskinesias. Because entacapone -- which prolongs the half-life of levodopa by inhibiting the enzyme COMT (catechol o-methyl transferase) -- is approved to reduce loss of motor function in late Parkinson's, Dr. Olanow and colleagues decided to test its use against development of dyskinesias in early disease. In their study, 745 patients who required initiation of levodopa were randomized to receive either levodopa/carbidopa (LC) or levodopa/carbidopa/entacapone (LCE). (Carbidopa is dosed with levodopa to reduce nausea.) Treatment continued for at least 134 weeks. The main outcome measure was time to onset of dyskinesias. Dyskinesias occurred earlier in patients receiving the entacapone combination than in those receiving LC, with 42% of the entacapone patients developing them after a mean of 74 weeks compared with 32% developing them after a mean of 79 weeks in the LC group (hazard ratio 1.29, P=0.038). Dr. Olanow suggested that the unexpected results might by explained by differences in total levodopa exposure between the two groups. Pharmacokinetic analysis showed that patients receiving the entacapone combination received significantly greater levodopa dose equivalents because of the larger area under the curve. "This likely accounted for these results," Dr. Olanow said. "There is no reason to begin entacapone in early Parkinson's disease," he said, in an attempt to delay dyskinesias. He noted that these results do not weaken the rationale for its use later in the disease. ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn