The role of COMT inhibition in the treatment of Parkinson's disease.

Several prospective double-blind, placebo-controlled trials have demonstrated that combining levodopa with the COMT inhibitor entacapone is efficacious in reducing motor fluctuations. Compared with levodopa alone, mean daily "on" time was increased by 1-1.7 hours, with a corresponding decrease in daily "off" time. In addition, some studies have shown that these benefits are associated with significant improvements in both UPDRS motor and ADL scores. These benefits have been shown to persist in long-term clinical trials with follow-up for up to 3 years. Recent studies have also examined the value of combining levodopa with entacapone in stable patients who do not experience motor response fluctuations. Here, too, benefits have been reported, especially in health-related quality of life measures. Studies to determine if administering levodopa in combination with entacapone will delay the development of dyskinesia and motor fluctuations are eagerly awaited.