Comparative efficacy and safety of irreversible (rasagiline) and reversible (safinamide) monoamine oxidase inhibitors as add-on therapy for Parkinson's disease.

Background: 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 novel medications that are indicated for PD. Safinamide (reversible) and rasagiline (Irreversible) are selective monoamine oxidase B inhibitors which work by decreasing the degradation of dopamine in the brain.

Objective: This network meta-analysis aimed to examine the efficacy and safety of both drugs as add-on therapy in patients with Parkinson's disease.

Methodology: 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.

Results: The search query resulted in 557 studies. After screening, 15 studies were included in the final analysis, totaling 5676 participants. Safinamide (100 mg) was associated with the highest change in UPDRS-III scores (SMD = 0.3007, 95% CI = [0.1710-0.4304], z-score = 4.54, p value =  < 0.0001, I2 = 55.8%, SUCRA = 71.17%), with rasagiline (1 mg) being a close contender with a SUCRA of 70.64%. Safinamide (50 mg) had the lowest odds of serious adverse events (SAEs) with OR = 0.4394 (95% CI = [0.2231-0.8652], z-score = - 2.38, p value = 0.0174, I2 = 0%, SUCRA = 99.34%). Safinamide (100 mg) had the second-lowest odds of SAEs (OR = 0.9575, 95% CI = [0.6520-1.4061], z-score = - 0.22, p value = 0.8246, I2 = 0%, SUCRA = 66.96%). Almost all the studies had a low risk of bias.

Conclusion: Safinamide (100 mg) has good efficacy outcomes, whereas safinamide (50 mg) has favorable safety outcomes as compared to rasagiline for add-on therapy for PD.