Comparative efficacy and safety of monoamine oxidase type B inhibitors plus channel blockers and monoamine oxidase type B inhibitors as adjuvant therapy to levodopa in the treatment of Parkinson's disease: a network meta‐analysis of randomized controlled trials

Abstract Background and purpose The monoamine oxidase type B inhibitors plus channel blockers (MAO‐BIs plus) are a new class of antiparkinsonian drug with additional mechanisms of action for their property as ion channel blockers. The present study aimed to compare the efficacy and safety of MAO‐BIs plus and conventional MAO‐BIs, as well as their corresponding doses, as adjuvant therapy to levodopa in the treatment of Parkinson's disease (PD). Method Randomized controlled trials enrolling PD patients treated with selegiline, rasagiline, safinamide or zonisamide as adjuvant therapy to levodopa were identified. Bayesian network meta‐analysis was conducted. Results Thirty‐one randomized controlled trials comprising 7142 PD patients were included. Compared with levodopa monotherapy, the combination therapy of MAO‐BIs and levodopa was significantly more effective, with a mean difference of 2.74 (1.26–4.18) on the Unified Parkinson's Disease Rating Scale (UPDRS) III score change for selegiline, 2.67 (1.45–3.87) for safinamide, 2.2 (0.98–3.64) for zonisamide and 2.04 (1.24–2.87) for rasagiline. No significant difference was detected amongst MAO‐BIs. The surface under the cumulative ranking results showed that safinamide 100 mg and rasagiline 1 mg ranked first in improving UPDRS III and UPDRS II, respectively. Zonisamide 100 mg ranked first in reducing OFF time. For safety outcomes, rasagiline was associated with a higher incidence of adverse events than placebo and safinamide. MAO‐BIs plus had a higher probability of being safer agents compared to conventional MAO‐BIs. Conclusions Monoamine oxidase type B inhibitors plus, conventional MAO‐BIs and the corresponding doses are similar in efficacy in PD treatment. MAO‐BIs plus might be safer than conventional MAO‐BIs. Head‐to‐head comparisons are needed for further investigation.