Objective: We conducted a double blind, placebo-controlled crossover study to examine clinical and neurophysiological effect of zolpidem in patients with task specific dystonia.

Background: Task specific dystonia is disabling movement disorder that includes writer’s cramp and musician dystonia. It causes impaired hand use and may lead to the termination of professional career. Currently, there is no effective treatment. Zolpidem, a short-acting hypnotic drug that binds to GABA –A receptor benzodiazepine site, has been reported to transiently improve various movement disorders, including a proportion of patients with primary focal and generalized dystonia. The mechanisms underlying its therapeutic effects has not been investigated.

Methods: Six patients with writer’s cramp and one guitarist with musician dystonia underwent transcranial magnetic stimulation (TMS) and 18F-FDG-PET brain imaging after single 5 mg dose of zolpidem and placebo, in four separate sessions. We measured resting motor threshold (RMT), active motor threshold (AMT), resting and active input/output (IO) curve, short interval intracortical inhibition (SICI) curve, long interval intracortical inhibition (LICI), intracortical facilitation (ICF) and cortical silent period (CSP). Clinical improvement was rated using writer’s cramp rating scale (WCRS). Clinical and TMS measures were compared using paired sample t-test or repeated measures ANOVA; correlations were tested using Spearman analysis. Statistical parametric mapping was used to identify zolpidem effect on global brain metabolism.

Results: There was significant improvement on WRCS on zolpidem. Zolpidem reduced the steepness of active IO curve, while there was no difference in AMT, RMT, resting IO curve, SICI, LICI, CSP and ICF on the group level. Significant positive correlation was found between clinical improvement and enhancement of LICI on zolpidem. 18F-FDG-PET revealed that zolpidem treatment was associated with hypometabolism in primary sensori-motor cortex, cerebellum and medial temporal lobes and hypermetabolism in caput nuclei caudate, parietal cortex and frontal regions.

Conclusions: Clinical effect of zolpidem in task specific dystonia was associated with evident changes in TMS measures of corticospinal excitability and intracortical inhibition and changes in brain metabolism on brain 18F-FGD-PET. Zolpidem may be an effective treatment in a proportion of patients with task specific dystonia.

References: 1. Lin, P. T. & Hallett, M. The pathophysiology of focal hand dystonia. J. Hand Ther. Off. J. Am. Soc. Hand Ther. 22, 109–114 (2009). 2. Konczak, J. & Abbruzzese, G. Focal dystonia in musicians: linking motor symptoms to somatosensory dysfunction. Front. Hum. Neurosci. 7, (2013). 3. Depoortere, H. et al. Zolpidem, a novel nonbenzodiazepine hypnotic. I. Neuropharmacological and behavioral effects. J. Pharmacol. Exp. Ther. 237, 649–658 (1986). 4. Abe, K. Zolpidem therapy for movement disorders. Recent Patents CNS Drug Discov. 3, 55–60 (2008). 5. Miyazaki, Y. et al. Efficacy of Zolpidem for Dystonia: A Study Among Different Subtypes. Front. Neurol. 3, (2012). 6. Martinez-Ramirez, D., Paz-Gomez, V. & Rodriguez, R. L. Response to zolpidem in oromandibular dystonia: a case report. Parkinsonism Relat. Disord. 21, 154–155 (2015). 7. Sunwoo, M. et al. A Case with Improvement of Blepharospasm by Zolpidem. J. Mov. Disord. 4, 53–54 (2011).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/zolpidem-effect-in-task-specific-dystonia-clinical-and-neurophysiological-study/