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Randomized Controlled Trial
. 2024 Apr;45(4):1725-1734.
doi: 10.1007/s10072-024-07396-w. Epub 2024 Feb 20.

Role of zonisamide in advanced Parkinson's disease: a randomized placebo-controlled study

Mohamed Essam  1 , Eman Hamid  1 , Eman Abushady  1 , Mahmoud El-Balkimy  1 , Angelo Antonini  2 , Ali Shalash  3
Affiliations
Randomized Controlled Trial

Role of zonisamide in advanced Parkinson's disease: a randomized placebo-controlled study

Mohamed Essam et al. Neurol Sci. 2024 Apr.

Abstract

Background: Zonisamide (ZNS) has shown some efficacy in motor symptoms of PD; however, more evidence is lacking, and its effects on nonmotor symptoms (NMSs) and quality of life (QoL) remain to be investigated. This randomized double-blinded placebo-controlled crossover study investigated the effect of ZNS on motor and NMS symptoms and QoL in advanced PD.

Methods: PD patients with Hoehn and Yahr stage ≥ 2 ("On" state) and at least 2 h off time daily were randomized to groups: ZNS 25 mg, ZNS 50 mg and placebo. Groups were assessed at baseline and at the 1- and 3-month follow-ups. The primary endpoint was the change in the total MDS-UPDRS III "On", while the secondary endpoint was the change in the total and parts I and IV MDS-UPDRS, Nonmotor Symptoms Scale and Parkinson's disease questionnaire-39 at the final assessment.

Results: Sixty-nine patients were assessed for efficacy at the 1-month follow-up, and 58 patients were assessed at the 3-month follow-up. The primary endpoint showed significant improvement in the ZNS 25 mg group compared to the placebo group (p = 0.009). At the final assessment, the ZNS 25 mg group showed significant improvement of total and part VI MDS-UPDRS, bradykinesia, tremor and functional impact of fluctuations compared to placebo. There was no change in dyskinesia, NMSs, QoL or side effects except for sedation.

Conclusion: ZNS has a favourable effect on motor symptoms in patients with wearing off as adjunctive therapy with other dopaminergic drugs, with no exacerbation of dyskinesia and a limited impact on NMSs and QoL.

Trial registration: Clinicaltrials.gov, NCT04182399, in 24/11/2019.

Keywords: Nonmotor symptoms; Parkinson̕ s disease; Quality of life; Wearing off; Zonisamide.

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Conflict of interest statement

The authors declare no competing interests.

Angelo Antonini has received compensation for consultancy and speaker-related activities from UCB, Britannia, AbbVie, Zambon, Bial, Ever Pharma, Theravance Biopharma, Roche, General Electric, Medscape. He receives research support from Chiesi Pharmaceuticals, Lundbeck, Bial, Movement Disorders Society, Horizon2020 Grant 825785, Horizon2020 Grant 101016902, Ministry of Education University and Research (MIUR) Grant ARS01_01081 and Cariparo Foundation. Other authors have no financial conflicts of interest to disclose, with no financial support or funding.

Figures

Fig. 1
Fig. 1
Randomization and distribution of the study population
Fig. 2
Fig. 2
A Mean MDS-UPDRS-III scores at different assessments within different groups (significant in the ZNS 50 mg group at 3 months (p = 0.003)). B Mean MDS-UPDRS-IV scores at different assessments within different groups (significant in the ZNS 50 mg group (p = 0.001) at 1 and 3 months)
See this image and copyright information in PMC

References

    1. Schiess N, Cataldi R, Okun MS, et al. Six action steps to address global disparities in Parkinson disease: a world health organization priority. JAMA Neurol. 2022;79(9):929–936. doi: 10.1001/jamaneurol.2022.1783. - DOI - PubMed
    1. Antonini A, Moro E, Godeiro C, Reichmann H. Medical and surgical management of advanced Parkinson’s disease. Mov Disord. 2018;33(6):900–908. doi: 10.1002/mds.27340. - DOI - PubMed
    1. Hamid E, Ayele BA, Massi DG, et al. Availability of therapies and services for Parkinson’s disease in Africa: a continent-wide survey. Mov Disord. 2021;36(10):2393–2407. doi: 10.1002/mds.28669. - DOI - PubMed
    1. Kwan SY, Chuang YC, Huang CW, Chen TC, Jou SB, Dash A. Zonisamide: review of recent clinical evidence for treatment of epilepsy. CNS Neurosci Ther. 2015;21(9):683–691. doi: 10.1111/cns.12418. - DOI - PMC - PubMed
    1. Murata M, Horiuchi E, Kanazawa I. Zonisamide has beneficial effects on Parkinson’s disease patients. Neurosci Res. 2001;41(4):397–399. doi: 10.1016/s0168-0102(01)00298-x. - DOI - PubMed

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