Pharmacologic treatment of advanced Parkinson's disease: A meta-analysis of COMT inhibitors and MAO-B inhibitors

Objective: To perform a meta-analysis of randomized placebo-controlled trials evaluating catechol-O-methyltransferase (COMT) inhibitors or monoamine oxidase type B (MAO-B) inhibitors in addition to levodopa versus levodopa alone for the treatment of advanced Parkinson's disease (PD). Methods: A systematic literature search was performed between 1990 and October 2007. The primary outcome measures assessed were the reduction in scores of Unified Parkinson's Disease Rating Scale (UPDRS) total, activities of daily living (ADL) and motor scores from baseline. Other efficacy and safety endpoints were also evaluated. Results: A total of 13 trials (n = 3775 subjects) were included in the meta-analysis. As compared to placebo, COMT and MAO-B inhibitor use resulted in greater improvement in UPDRS total score (weighted mean difference [WMD] -2.13, 95%CI -0.46 to -0.20; and WMD -5.03, 95%CI -7.38 to -2.68) ADL scores (WMD -0.99, 95%CI -1.56 to -0.43; and WMD -1.48, 95%CI -2.13 to -0.83) and motor scores (WMD -1.50, 95%CI -2.70 to -0.30; and WMD -3.19, 95%CI -4.57 to -1.80) as well as increase in on time, reduction in off' time and decreased need in levodopa dose compared to placebo. Incidences of dyskinesia were significantly higher with the COMT and MAO-B inhibitors compared to placebo. Conclusion: The use of COMT or MAO-B inhibitors plus levodopa is superior to levodopa alone at reducing PD symptoms in patients with advanced PD. While combination therapies with COMT or MAO-B inhibitor plus levodopa seem especially useful amongst PD patients with wearing-off phenomenon, they are associated with more adverse events. (C) 2008 Elsevier Ltd. All rights reserved.