A Randomized, Controlled, Double-Blind, Crossover Trial of Zonisamide in Myoclonus-Dystonia

Neurology. 2016 May 3;86(18):1729-35. doi: 10.1212/WNL.0000000000002631. Epub 2016 Apr 6.


Objective: To evaluate the efficacy and safety of zonisamide in patients with myoclonus-dystonia.

Methods: We conducted a randomized, double-blind, placebo-controlled crossover trial of zonisamide (300 mg/d) in 24 patients with myoclonus-dystonia. Each treatment period consisted of a 6-week titration phase followed by a 3-week fixed-dose phase. The periods were separated by a 5-week washout period. The co-primary outcomes were action myoclonus severity (section 4 of the Unified Myoclonus Rating Scale [UMRS 4]) and myoclonus-related functional disability (UMRS 5). Secondary outcomes included dystonia severity, assessed with the movement and disability subscales of the Burke-Fahn-Marsden-Dystonia Rating Scale (BFM), the Clinical Global Impression-Improvement scale (CGI), and safety measures. Wilcoxon signed-rank tests for paired data were used to analyze treatment effects.

Results: Twenty-three patients (11 men, 12 women) were analyzed in the intention-to-treat analysis. Zonisamide significantly improved both action myoclonus (median improvement [95% confidence limits] -5 [-9.25 to -1.44], p = 0.003) and myoclonus-related functional disability (median improvement [95% confidence limits] -2 [-2.58 to -2.46], p = 0.007) compared to placebo. Zonisamide also significantly improved dystonia (BFM movement) compared to placebo (median improvement [95% confidence limits] -3 [-8.46 to 0.03], p = 0.009). No difference was found between zonisamide and placebo with respect to the CGI (median improvement [95% confidence limits] -1 [-1.31 to 0.09], p = 0.1). Zonisamide was well-tolerated.

Conclusions: Zonisamide is well-tolerated and effective on the motor symptoms of myoclonus-dystonia.

Classification of evidence: This study provides Class I evidence that zonisamide improves myoclonus and related disability in patients with myoclonus-dystonia.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Central Nervous System Agents / adverse effects
  • Central Nervous System Agents / blood
  • Central Nervous System Agents / therapeutic use*
  • Cross-Over Studies
  • Disability Evaluation
  • Double-Blind Method
  • Dystonic Disorders / blood
  • Dystonic Disorders / drug therapy*
  • Dystonic Disorders / genetics
  • Female
  • Humans
  • Isoxazoles / adverse effects
  • Isoxazoles / blood
  • Isoxazoles / therapeutic use*
  • Male
  • Sarcoglycans / genetics
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult
  • Zonisamide


  • Central Nervous System Agents
  • Isoxazoles
  • SGCE protein, human
  • Sarcoglycans
  • Zonisamide

Supplementary concepts

  • Myoclonic dystonia