Zolpidem for the Treatment of Neurologic Disorders

Abstract

IMPORTANCE Given its selective action on the ω1 subtype of the γ-aminobutyric acid A receptor, zolpidem tartrate presents a potential treatment mechanism for other neurologic disorders.OBJECTIVE To synthesize studies that used zolpidem to treat neurologic disorders.EVIDENCE REVIEW Eligibility criteria included any published English-language article that examined the use of zolpidem for noninsomnia neurologic disorders in humans for all dates up to March 20, 2015. Searched databases included PubMed, Scopus, Web of Science Core Collection, the Cochrane Library, EMBASE, CENTRAL, and clinicaltrials.gov. Publication bias was mitigated by searching clinicaltrials.gov for unpublished studies. Two rounds of screening were performed based on title and then abstract, and coding was performed by 2 coders. All methods followed the PRISMA Reporting Guidelines for systematic reviews of the literature.FINDINGS The initial search produced 2314 articles after removing duplicates. After exclusion based on a review of abstracts, 67 articles remained for full manuscript review. Thirty-one studies treated movement disorders, 22 treated disorders of consciousness, and 14 treated other neurologic conditions, including stroke, traumatic brain injury, encephalopathy, and dementia. Study designs included case reports (n = 28), case series (n = 8), single-patient interventional (n = 13), pretest and posttest (n = 9), randomized clinical trials (n = 9), and crossover studies (n = 5). Only 11 studies had more than 10 participants. Effects of zolpidem were wide ranging (eg, improvement on the JFK Coma Recovery Scale-Revised, the Unified Parkinson Disease Rating Scale, and the Burke-Fahn-Marsden Dystonia Rating Scale) and generally lasted 1 to 4 hours before the participant returned to baseline. Sedation was the most common adverse effect.CONCLUSIONS AND RELEVANCE Zolpidem has been observed to transiently treat a large variety of neurologic disorders, most often related to movement disorders and disorders of consciousness. Much of what is known comes from case reports and small interventional trials. These findings may represent a new treatment mechanism for these disorders.

Effect of Zolpidem in the Aftermath of Traumatic Brain Injury: An MEG Study

“…is transient counterintuitive effect of zolpidem, a commonly used hypnotic, has been observed in many people with a variety of neurological disorders. While this effect has been well documented in the literature, much still remains to be understood [11].…”

“…Since then, there have been many reports where zolpidem has been used to treat a variety of neurological disorders of consciousness [5][6][7][8][9][10]. In a systematic review, Bomalaski and colleagues discussed the literature regarding the potential of zolpidem to treat a variety of neurological disorders and concluded that more research is needed to interrogate the complex underlying neurophysiological mechanisms involved and in order to understand zolpidem's usefulness as a therapeutic drug [11].…”

Emulated Clinical Trials from Longitudinal Real-World Data Efficiently Identify Candidates for Neurological Disease Modification: Examples from Parkinson’s Disease

“…In fact, a single prior report published more than two decades ago speculated that zolpidem would not be efficacious for PD, based on the limited clinical experience with the drug at the time, without specific consideration for cognition (Lavoisy and Marsac, 1997). However, recent publications demonstrate Zolpidem’s ability to treat a large variety of neurologic disorders, most often related to movement disorders and disorders of consciousness, and suggest zolpidem induces transient effects on UPDRS (Bomalaski et al, 2017). Of note, several cross-sectional reports have raised concerns for increased risk of reversible dementia or Alzheimer’s diseases in the general population when exposed to zolpidem (Shih et al, 2015; Lee et al, 2018).…”

Effects of zolpidem on sleep parameters in patients with cirrhosis and sleep disturbances: A randomized, placebo-controlled trial

“…In fact there are some reports of development of periodic limb movement during zolpidem treatment especially in elderly females [24]. On the other hand, zolpidem has been found to be effective in a variety of movement disorders [25].…”