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

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.

Fig. 1

Randomization and distribution of the study population

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)