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Efficacy and Safety of MAO-B Inhibitors Safinamide and Zonisamide in Parkinson’s Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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Abstract

Background and Objective

In Parkinson’s disease, safinamide and zonisamide are novel monoamine oxidase-B inhibitors with a dual mechanism of action involving the inhibition of sodium and calcium channels and the subsequent release of glutamate. The aim of this systematic review and meta-analysis was to examine the efficacy and safety of both drugs compared with placebo on motor symptoms, cognitive function, and quality of life in patients with Parkinson’s disease.

Methods

We searched MEDLINE, EMBASE, Cochrane Central, Scopus, PsycINFO, and trials registries up to March 2023 for randomized controlled trials of adults with Parkinson’s disease administered either safinamide or zonisamide and published in English. We excluded single-arm trials or if neither the efficacy nor safety outcomes of interest were reported. Primary outcomes were the change from baseline in Unified Parkinson’s Disease Rating Scale section III (UPDRS-III) and serious adverse events. Secondary outcomes included a change from baseline in OFF-time, Parkinson’s Disease Questionnaire 39 to evaluate quality of life, and Mini-Mental State Examination for cognitive function assessment. The meta-analysis was conducted using Review Manager 5.4.1. Random-effect models were used to calculate the pooled mean differences (MDs) and risk ratios with 95% confidence intervals (CIs). Subgroup analyses by medication, doses, Parkinson’s disease stage, and risk of bias were conducted. We assessed the risk of bias using the Cochrane’s risk of bias tool. Sensitivity analysis was conducted, and publication bias were evaluated. This meta-analysis was not externally funded, and the protocol is available on the Open Science Framework Registration (https://doi.org/10.17605/OSF.IO/AMNP5).

Results

Of 3570 screened citations, 16 trials met inclusion criteria (4314 patients with Parkinson’s disease). Ten safinamide trials were conducted in several countries. Six zonisamide trials were included, five of which were conducted in Japan and one in India. UPDRS Part III scores were significantly lower with both monoamine oxidase-B inhibitors than with placebo (MD = −  2.18; 95% CI −  2.88 to −  1.49; I 2 =63%; n = 14 studies). A subgroup analysis showed a significant improvement in UPDRS-III in safinamide (MD = −  2.10; 95% CI −  3.09 to −  1.11; I2 = 71%; n = 8 studies) and zonisamide (MD = −  2.31; 95% CI −  3.35 to −  1.27; I2 = 52%; n = 6 studies) compared with placebo. Monoamine oxidase-B inhibitors significantly decreased OFF-time compared with placebo. No significant differences in cognitive function (Mini-Mental State Examination), whereas an improvement in quality of life (Parkinson’s Disease Questionnaire 39 scores) was observed. There was no significant difference in incidence rates of serious adverse events among all examined doses of zonisamide and safinamide compared with placebo. Two trials were reported as a high risk of bias and sensitivity analyses confirmed the primary analysis results.

Conclusions

Evidence suggests that novel monoamine oxidase-B inhibitors not only improve motor symptoms but also enhance patients’ quality of life. The meta-analysis showed that both medications have a similar safety profile to placebo with regard to serious adverse events. The overall findings emphasize the effectiveness of safinamide and zonisamide in the treatment of Parkinson’s disease as adjunct therapy. Further long-term studies examining the impact of these medications on motor and non-motor symptoms are necessary.

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Acknowledgments

The authors acknowledge the University of Manitoba Library for the peer review of the MEDLINE search strategy.

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Authors and Affiliations

  1. College of Pharmacy, University of Manitoba, Winnipeg, MB, R3E 0T5, Canada

    Laila Aboulatta, Lara Haidar, Alekhya Lavu, Payam Peymani & Sherif Eltonsy

  2. George & Fay Yee Center for Healthcare Innovation, University of Manitoba, Winnipeg, MB, Canada

    Ahmed Abou-Setta & Rasheda Rabbani

  3. Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada

    Ahmed Abou-Setta & Ryan Zarychanski

  4. WRHA Virtual Library, University of Manitoba, Winnipeg, MB, Canada

    Nicole Askin

  5. Cancer Care Manitoba, Winnipeg, MB, Canada

    Ryan Zarychanski

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Laila Aboulatta, Lara Haidar, Ahmed Abou-Setta, Nicole Askin, Rasheda Rabbani, Alekhya Lavu, Payam Peymani, Ryan Zarychanski, and Sherif Eltonsy have no conflicts of interest that are directly relevant to the content of this article.

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Authors’ Contributions

LA, AA, RR, RZ, NA, and SE contributed to the conception and design of the study. LA and NA performed the literature search. LA, LH, AL, and PP conducted the screening and data extraction. LA conducted the data analysis. LA, AA, RR, and SE contributed to the data interpretation. LA drafted the manuscript. AA, RR, RZ, NA, PP, AL, LH, and SE critically revised the manuscript. All authors have read and approved the final submitted manuscript and agree to be accountable for the work.

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Aboulatta, L., Haidar, L., Abou-Setta, A. et al. Efficacy and Safety of MAO-B Inhibitors Safinamide and Zonisamide in Parkinson’s Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. CNS Drugs 37, 941–956 (2023). https://doi.org/10.1007/s40263-023-01048-x

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