The Safety and Efficacy of Monoamine Oxidase-B Inhibitors as Add-on Therapy to Dopamine Agonists for the Treatment of Parkinson’s Disease: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials
Faizan Shahzad1, Momina Siddiqui1, Aamna Khan1, Fahad Shabbir1, Mohamed Hisham Alamin2, Humza Saeed1, . Abdullah1, Syed Ijlal Ahmed3
1Rawalpindi Medical University, 2International University of Africa, 3Saint Francis Medical Center
Objective:
This meta-analysis aimed to examine the efficacy and safety of both irreversible and reversible monoamine oxidase B (MAO-B) inhibitors as add-on therapy in patients with Parkinson’s disease.
Background:
Parkinson's disease (PD) is a neurodegenerative disease, treated with carbidopa/levodopa or a dopamine agonist. MAO-B inhibitors are given adjunctively to L-DOPA in the case of advanced Parkinson’s Disease. They help increase dopamine’s concentration by reducing the enzymatic breakdown of dopamine within the synapse. They can be irreversible (selegiline and rasagiline) or reversible (safinamide).
Design/Methods:
We searched PubMed, Cochrane, and Embase for Randomized Controlled Trials published till September 2025. Primary outcomes were the change in the Unified Parkinson’s Disease Rating Scale (UPDRS-III) score and treatment-emergent adverse effects (TEAE). Risk ratios (RR) and Standardized Mean Differences (SMD) were calculated with a 95% confidence interval using a random effects approach. Heterogeneity was measured using the I2 test. Comparative efficacy was assessed via the Surface Under Cumulative Ranking Curve (SUCRA). The risk of bias in studies was calculated using Cochrane's RoB 2.0.
Results:
19 studies were included in the final analysis, totaling 6086 participants. Selegiline (10mg/day) was associated with the highest change in UPDRS-III Scores (SMD=-0.3519, 95% CI=-0.4873 to -0.2165, p<0.0001, I2=46.6%, SUCRA= 79.21%). However, it was associated with a significant risk of adverse events (RR=1.1135, 95% CI=0.9983 to 1.2420, p=0.0536, I2=28.8%, SUCRA=26.79%). Safinamide (100mg) also had good efficacy (SMD=-0.2981, 95% CI=-0.4196 to -0.1767, p< 0.0001, SUCRA=65.86%) with a relatively better safety profile (RR=1.0301, 95% CI=0.9388 to 1.1303, p=0.5312, SUCRA=56.40%). Almost all the studies had a low risk of bias.
Conclusions:
Selegiline (10mg/day) and safinamide (100mg) offer good therapeutic benefit as add-on therapy for PD. However, safinamide (100mg) has a relatively better safety profile as compared to selegiline (10mg/day). Further research should emphasize on long-term effects of these drugs through longitudinal studies focusing on patient-reported outcomes.
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