Highlights
- •No significant improvement in tremor with Zonisamide compared to placebo.
- •There was a trend for greater improvement in tremor compared to placebo.
- •A best-case analysis showed a significant difference between the groups.
- •Greater improvement in total UPDRS and TETRAS score compared to placebo was found.
- •This study showed a safe adverse effect profile with a low dose of Zonisamide.
Abstract
Introduction
and objective: Tremor is a disabling symptom of PD that usually responds poorly to
available standard pharmacological agents. This study aimed to assess the effect of
Zonisamide 25 mg on tremor in tremor-dominant PD patients as compared to placebo.
Methods
This was a randomized, placebo-controlled, double-blind study. Parkinson's disease
patients were allocated either to the intervention group (standard treatment along
with Zonisamide 25 mg add-on) or the placebo group (standard treatment along with
placebo). Baseline Unified Parkinson's Disease Rating Scale (UPDRS) and Tremor Research
Group Essential Tremor Rating Scale (TETRAS) scores, as well as accelerometric tremor
analysis were done and follow-up assessments of the same were done after 12 weeks
of intervention. Percentage change from baseline in the UPDRS tremor score was the
primary outcome whereas percentage change from baseline of total UPDRS score, UPDRS
rigidity and bradykinesia scores, TETRAS score, and accelerometric tremor analysis
values were the secondary outcomes.
Results
There was no significant difference in the percentage change from baseline UPDRS tremor
scores between the two groups (placebo: 8.33 [-19.89–23.86] vs drug: 26.14 [-35.58
to −16.07], p-value: 0.164, CI: 0.157–0.171). Best-case analysis for missing values
showed a significant improvement in the drug group, compared to the placebo group
(p-value: < 0.001, CI: <0.001 - <0.001).
Conclusion
Zonisamide at a dose of 25 mg per day did not improve tremor in tremor-dominant PD
patients, however, a positive trend was seen as compared to Placebo in the UPDRS tremor
score. Larger studies are required to confirm this finding.
Keywords
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References
- Tremor-predominant Parkinson's disease. Approaches to treatment.Drugs Aging. 2000; 16: 273-278https://doi.org/10.2165/00002512-200016040-00003
- Treatment of tremor in Parkinson's disease by subthalamic nucleus stimulation.Mov. Disord. Off. J. Mov. Disord. Soc. 1998; 13: 907-914https://doi.org/10.1002/mds.870130608
- High-frequency stimulation of the globus pallidus for the treatment of Parkinson's disease.Neurology. 1997; 49: 249-253https://doi.org/10.1212/wnl.49.1.249
- Zonisamide has beneficial effects on Parkinson's disease patients.Neurosci. Res. 2001; 41: 397-399https://doi.org/10.1016/s0168-0102(01)00298-x
- Zonisamide improves motor function in Parkinson disease: a randomized, double-blind study.Neurology. 2007; 68: 45-50https://doi.org/10.1212/01.wnl.0000250236.75053.16
- Zonisamide improves wearing-off in Parkinson's disease: a randomized, double-blind study.Mov. Disord. Off. J. Mov. Disord. Soc. 2015; 30: 1343-1350https://doi.org/10.1002/mds.26286
- Effects of T-type calcium channel blockers on a parkinsonian tremor model in rats.Pharmacol. Biochem. Behav. 2011; 97: 656-659https://doi.org/10.1016/j.pbb.2010.11.014
- A double-blind placebo-controlled trial of zonisamide (zonegran) in the treatment of essential tremor.Mov. Disord. Off J. Mov. Disord. Soc. 2007; 22: 279-282https://doi.org/10.1002/mds.21282
- Zonisamide for essential tremor.Clin. Neuropharmacol. 2007; 30: 345-349https://doi.org/10.1097/WNF.0b013e318074dd4f
- Zonisamide for essential tremor: an evaluator-blinded study.Mov. Disord. Off J. Mov. Disord. Soc. 2009; 24: 437-440https://doi.org/10.1002/mds.22418
- UK Parkinson's Disease Society Brain Bank Diagnostic Criteria.NIHR Journals Library, 2016https://www.ncbi.nlm.nih.gov/books/NBK379754/Date accessed: June 27, 2022
- Course in Parkinson disease subtypes: a 39-year clinicopathologic study.Neurology. 2009; 73: 206-212https://doi.org/10.1212/WNL.0b013e3181ae7af1
- Potential reliability and validity of a modified version of the Unified Parkinson's Disease Rating Scale that could be administered remotely.Park. Relat. Disord. 2013; 19: 218-221https://doi.org/10.1016/j.parkreldis.2012.10.008
- [Effect of zonisamide on resting tremor resistant to antiparkinsonian medication].No Shinkei. 2003; 55: 685-689
- Actigraphic study of tremor before and after treatment with zonisamide in patients with Parkinson's disease.Park. Relat. Disord. 2012; 18: 906-908https://doi.org/10.1016/j.parkreldis.2012.04.007
- Gender differences in Parkinson's disease.J. Neurol. Neurosurg. Psychiatry. 2007; 78: 819-824https://doi.org/10.1136/jnnp.2006.103788
- Gender differences in determinants and consequences of health and illness.J. Health Popul. Nutr. 2007; 25: 47-61
- Levodopa and the progression of Parkinson's disease.N. Engl. J. Med. 2004; 351: 2498-2508https://doi.org/10.1056/NEJMoa033447
- A review of the use of zonisamide in Parkinson's disease.Ther. Adv. Neurol. Disord. 2009; 2: 313-317https://doi.org/10.1177/1756285609338501
- Zonisamide in Parkinson's disease: a current update.Neurol. Sci. Off. J Ital Neurol. Soc. Ital. Soc. Clin. Neurophysiol. 2021; 42: 4123-4129https://doi.org/10.1007/s10072-021-05550-2
- Zonisamide for the treatment of Parkinson disease: a current update.Front. Neurosci. 2020; 14574652https://doi.org/10.3389/fnins.2020.574652
- Effects of zonisamide on dopaminergic system.Epilepsy Res. 1995; 22: 193-205
- Novel dopamine releasing response of an anti-convulsant agent with possible anti-Parkinson’s activity.J. Neural. Transm. 2004; 111: 713-724
- Variable expression of Parkinson's disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group.Neurology. 1990; 40: 1529-1534https://doi.org/10.1212/wnl.40.10.1529
- Differences in brain activation between tremor- and nontremor-dominant Parkinson disease.JAMA Neurol. 2013; 70: 100-106https://doi.org/10.1001/jamaneurol.2013.582
Article info
Publication history
Published online: October 24, 2022
Accepted:
October 13,
2022
Received in revised form:
October 13,
2022
Received:
July 11,
2022
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.