Introduction: The objective of this study was to evaluate the effects and safety of monoamine oxidase-B inhibitors (MAO-B inhibitors) for early Parkinson’s disease (PD). Methods: All studies that assessed the efficacy of MAO-B inhibitors in patients with early PD were searched. Publications were screened, and data were extracted according to predefined criteria. Rev Man 5.4 and Stata 14.0 software were used for statistical analysis. Outcomes assessed included change of Unified Parkinson’s Disease Rating Scale (UPDRS) total score, UPDRS part II score, UPDRS part III score, and the incidence of adverse events. Results: Thirty trials were identified and included in this meta-analysis. Compared with placebo, rasagiline, selegiline, safinamide, and zonisamide were significantly more effective, with a standardized mean difference (SMD) of −0.41 (95% confidence interval (CI) = −0.64 to −0.18), SMD = −0.38 (95% CI = −0.51 to −0.24), SMD = −0.37 (95% CI = −0.54 to −0.21), and SMD = −0.31 (95% CI = −0.57 to −0.05) on the UPDRS III score change, respectively. The surface under the cumulative ranking results showed that rasagiline ranked first in improving UPDRS II and UPDRS III, respectively. For safety outcomes, safinamide combination with dopaminergic treatment had lower risk of incurring any adverse events (risk ratio = 0.1, 95% CI = 0.01–0.2), and no statistical difference in incidence of adverse events was observed among other MAO-B inhibitor regimes and placebo. Conclusion: Rasagiline, selegiline, safinamide, and zonisamide were effective compared to placebo in the treatment of early PD, but rasagiline was the most effective drug. As for safety, safinamide combination with dopaminergic treatment had lower risk of incurring any adverse events.

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