Zonisamide add-on in tremor-dominant Parkinson's disease- A randomized controlled clinical trial

Pillai, Kanchana Soman; Bhat, Pallavi; Srivastava, Achal; Rajan, Roopa; Radhakrishnan, Divya M.; Elavarasi, Arunmozhimaran; Srivastava, MV Padma; Singh, Mamta Bhushan; Vishnu, V.Y.; Prasad, Kameshwar; Pandit, Awadh Kishor; Goyal, Vinay

doi:10.1016/j.parkreldis.2022.10.017

Cited by 3 publications

(1 citation statement)

References 21 publications

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“…A pilot study reported improvement of rest tremor in 7 out of 9 PD patients with ZNS 100 mg [ 29 ]. A recent randomized, placebo-controlled, double-blind study examined the effect of ZNS 25 mg on tremor in 19 tremor-dominant PD patients compared to 18 patients in the placebo group and showed a positive trend of UPDRS tremor score [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

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

Essam,

Hamid,

Abushady

et al. 2024

Neurol Sci

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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.

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Section: Discussionmentioning

confidence: 99%

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

Essam,

Hamid,

Abushady

et al. 2024

Neurol Sci

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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

Aboulatta,

Haidar,

Abou-Setta

et al. 2023

CNS Drugs

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Single-neuron neurodegeneration as a degenerative model for Parkinson’s disease

Huenchuguala

Segura‐Aguilar

2023

Neural Regeneration Research

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The positive effect of levodopa in the treatment of Parkinson’s disease, although it is limited in time and has severe side effects, has encouraged the scientific community to look for new drugs that can stop the neurodegenerative process or even regenerate the neuromelanin-containing dopaminergic nigrostriatal neurons. Successful preclinical studies with coenzyme Q10, mitoquinone, isradipine, nilotinib, TCH346, neurturin, zonisamide, deferiprone, prasinezumab, and cinpanemab prompted clinical trials. However, these failed and after more than 50 years levodopa continues to be the key drug in the treatment of the disease, despite its severe side effects after 4–6 years of chronic treatment. The lack of translated successful results obtained in preclinical investigations based on the use of neurotoxins that do not exist in the human body as new drugs for Parkinson’s disease treatment is a big problem. In our opinion, the cause of these failures lies in the experimental animal models involving neurotoxins that do not exist in the human body, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine, that induce a very fast, massive and expansive neurodegenerative process, which contrasts with the extremely slow one of neuromelanin-containing dopaminergic neurons. The exceedingly slow progress of the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s patients is due to (i) a degenerative model in which the neurotoxic effect of an endogenous neurotoxin affects a single neuron, (ii) a neurotoxic event that is not expansive and (iii) the fact that the neurotoxin that triggers the neurodegenerative process is produced inside the neuromelanin-containing dopaminergic neurons. The endogenous neurotoxin that fits this degenerative model involving one single neuron at a time is aminochrome, since it (i) is generated within neuromelanin-containing dopaminergic neurons, (ii) does not cause an expansive neurotoxic effect and (iii) triggers all the mechanisms involved in the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s disease. In conclusion, based on the hypothesis that the neurodegenerative process of idiopathic Parkinson’s disease corresponds to a single-neuron neurodegeneration model, we must search for molecules that increase the expression of the neuroprotective enzymes DT-diaphorase and glutathione transferase M2-2. It has been observed that the activation of the Kelch-like ECH-associated protein 1/nuclear factor (erythroid-derived 2)-like 2 pathway is associated with the transcriptional activation of the DT-diaphorase and glutathione transferase genes.

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Zonisamide add-on in tremor-dominant Parkinson's disease- A randomized controlled clinical trial

Cited by 3 publications

References 21 publications

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

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

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

Single-neuron neurodegeneration as a degenerative model for Parkinson’s disease

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