This network meta-analysis aimed to examine the efficacy and safety of Safinamide and Rasagiline as add-on therapy in patients with Parkinson’s disease.

Parkinson’s disease (PD) is a progressive, neurodegenerative condition caused by progressive loss of dopaminergic neurons of the substantia nigra. Safinamide and rasagiline are both medications that are indicated as add-on therapy for PD. They are both, reversible and irreversible respectively, selective monoamine oxidase B inhibitors which work by decreasing the degradation of dopamine in the brain. 

A systematic literature search of Pubmed, Embase, and Cochrane databases was conducted in September 2024. Primary outcomes were Changes in the Unified Parkinson’s Disease Rating Scale (UPDRS-III) and adverse effects. Standardized mean difference (SMD) and odds ratio (OR) were calculated with 95% confidence intervals. Surface Under Cumulative Ranking Curve (SUCRA) was used to compare individual interventions. The Cochrane risk-of-bias tool for randomized trials (RoB 2) was used to assess the risk of bias in studies.

The search query resulted in 557 studies. After screening, 15 studies were included in the final analysis, totaling 5676 participants. Safinamide (200mg) was associated with the highest change in UPDRS-III Scores (SMD= 0.4622, 95% CI= [ 0.1748 to 0.7496], p-value= 0.0016, SUCRA= 84.48%). Safinamide (200mg) was also associated with the lowest odds of incidence of adverse events (OR= 0.6222, 95% CI= [0.2996 to 1.2922], p-value= 0.2032, SUCRA= 87.66%). Whereas, safinamide (50mg) was associated with the lowest odds of serious adverse events (OR= 0.4676, 95% CI= [0.2380 to 0.9188], p-value= 0.0274, SUCRA= 95.88%). Almost all the studies had a low risk of bias.

Safinamide (200mg) has better outcomes of efficacy and safety as compared to rasagiline for add-on therapy for PD. Further research should emphasize on long-term effects of safinamide through longitudinal studies focusing on patient-reported outcomes.