Meta-analysis of the comparative efficacy and safety of adjuvant treatment to levodopa in later Parkinson's disease

Background: Levodopa initially provides good symptomatic control of the symptoms of Parkinson's disease, but motor complications often develop after long‐term use. Other classes of antiparkinsonian drugs including dopamine agonists, catechol‐O‐methyl transferase inhibitors, or monoamine oxidase type B inhibitors are then added as adjuvant therapy. It is unclear whether one class of drug is more effective than another. This meta‐analysis evaluates the comparative benefits and risks of these agents as adjuvant treatment in Parkinson's disease patients with motor complications. Methods: A systematic review of the literature from 1966 to the end of June 2010 was conducted to identify randomized trials involving a dopamine agonist, catechol‐O‐methyl transferase inhibitor, or monoamine oxidase type B inhibitor versus placebo, as adjuvant to levodopa therapy. Results: Forty‐five trials involving nearly 9,000 participants were included. The meta‐analysis confirms reports from individual trials that compared with placebo, adjuvant therapy significantly reduces patient off‐time and levodopa dose, with improved symptom severity scores (e.g., Unified Parkinson's Disease Rating Scale). However, dyskinesia and numerous other side effects are increased with adjuvant therapy. Few randomized comparisons between drugs have been undertaken, but indirect comparisons suggest that dopamine agonist therapy may be more effective than catechol‐O‐methyl transferase inhibitor and monoamine oxidase type B inhibitor therapy, which have comparable efficacy. No differences between drugs within each class were observed other than the catechol‐O‐methyl transferase inhibitor tolcapone appearing more efficacious than entacapone. Discussion: This meta‐analysis highlights the need for direct head‐to‐head randomized trials to assess the impact of adjuvant therapy on patient‐rated quality of life and health economic outcomes. © 2011 Movement Disorder Society