Indirect meta-analysis of randomised placebo-controlled clinical trials on rasagiline and selegiline in the symptomatic treatment of Parkinson's disease

Introduction: Selegiline and rasagiline are established in the treatment of Parkinson's disease. As no direct comparative randomised controlled trials on these drugs are available, an indirect meta-analysis was conducted. Objective: Goal of the meta-analysis was to examine the clinical differentiation between rasagiline and selegiline based on efficacy and safety in Parkinson's disease. Methods: Literature databases, study registries and references of relevant publications were the basis of our literature search. Studies were selected according to Jadad and Delphi criteria. The analysis used a fixed effects model based on standardised mean differences for efficacy criteria and risk differences of safety outcomes. As outcomes, UPDRS (primary) and UPDRS motor functions, mental and ADL, the Schwab and England scale, the off-time as well as safety as secondary outcomes were used. Results: Rasagiline showed a statistically significant advantage in the primary endpoint UPDRS total scores (monotherapy: p=. 0.048, sensitivity analysis: p=. 0.023; pooled analyses: p=. 0.043, sensitivity analysis p=. 0.014) and the secondary endpoint UPDRS motor functions (monotherapy: p=. 0.049, sensitivity analysis p=. 0.031; pooled analyses: not significant, sensitivity analysis: p=. 0.046). For the other secondary outcome parameters, a numerical advantage for rasagiline was found. Discontinuation rates due to adverse effects showed a tendency in favour of rasagiline. Risk for adverse events such as dizziness, hallucinations, diarrhoea and syncope were lower with rasagiline than selegiline (each p<. 0.15). Conclusion: This meta-analysis showed a statistically significant and clinically relevant advantage for rasagiline over selegiline in the primary endpoint. The superiority of rasagiline was further substantiated with advantages in tolerability and safety. © 2012 Elsevier GmbH.