Zolpidem for the Treatment of Dystonia

Abstract

Background and Purpose: There are recent reports of zolpidem being effective for the treatment of a variety of movement disorders, due to its action on the gamma-aminobutyric acid A receptors in the thalamus, subthalamic nucleus, and globus pallidus, hence facilitating inhibitory pathways in the basal ganglia motor loop. Its beneficial effects have been described for Parkinson's disease and other related disorders. The objective of this study was to assess the therapeutic effects of zolpidem for various types of dystonia. Methods: We conducted a literature search using MEDLINE via PubMed, Cochrane Library, EMBASE, Scopus, and Google Scholar. Results: There were no randomized controlled trials. The literature included 6 case reports, 4 case series, and 1 non-randomized, non-controlled interventional trial. Overall, 49 adult participants (range 1–34 participants) with a mean age of 49.5 years were treated. Regardless of the dystonia subtype, a single dose of zolpidem at 10 mg causes improvement of symptoms for a mean duration of 3.4 h until patient returns to baseline. The main adverse effect noted was drowsiness, which was dose-dependent. Conclusion: While the current available literature suggests that zolpidem may be an effective pharmacologic option for treating dystonia, however the quality of evidence remains limited. Larger sample size, methodological consistency, and randomized controlled trials with long-term patient follow-ups are necessary to come up with definitive conclusion.

A novel preclinical secondary pharmacology resource illuminates target-adverse drug reaction associations of marketed drugs

“…Therefore, HRH2 inhibition by citalopram may contribute to its observed effects on the digestive system. Zolpidem, a GABA agonist used for treating insomnia, inhibited CHRM1 (AC50 = 0.21 µM), potentially contributing to its observed effect on dystonia 22 .…”

Efficacy and Safety of Zolpidem for Focal Dystonia After Neurosurgical Treatments: A Retrospective Cohort Study

“…In the basal ganglia, the ventral pallidum, substantia nigra pars reticulata, and subthalamic nucleus have the highest density of zolpidem-binding GABA-A receptors, suggesting that zolpidem may help restore the influence of basal ganglia output on the thalamus and motor cortex ( 26 , 27 ). Badillo et al suggested that the effects of zolpidem result from the facilitation of inhibitory pathways in the basal ganglia-thalamo-cortical circuit, which leads to the improvement of dystonia ( 13 ). However, zolpidem also has therapeutic effects on motor symptoms of Parkinson's disease, which is a hypokinetic movement disorder ( 28 – 30 ).…”

“…Zolpidem was reported to have therapeutic effects on Parkinson's disease, which was confirmed by several studies including a double-blinded, placebo-controlled study. Additionally, several reports have shown significant efficacy of zolpidem for dystonia ( 4 – 13 ). However, zolpidem remains an anecdotal treatment due to the lack of randomized and controlled studies, and the mechanism of action of zolpidem in relieving dystonia remains unclear.…”

Multimodal neurometabolic investigation of the effects of zolpidem on leukoencephalopathy‐related apathy

“…Zolpidem is specific for GABA1 receptors containing the a1 subunit, which are predominantly expressed in the thalamus and the striatum [31][32][33][34]. Zolpidem binding may inhibit the internal pallidum, which in turn may disinhibit the thalamus and activate thalamo-cortical projections, resulting in a 'deep brain stimulation-like' effect [35,36].…”