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Insomnia Drug Zolpidem Not Just for Insomnia?


June 29, 2017

By Reuters Staff

NEW YORK (Reuters Health) - The insomnia drug zolpidem can transiently help treat several neurologic disorders, most often movement disorders including Parkinson's disease and dystonia, and disorders of consciousness including coma and vegetative states, a systematic review indicates.

"We saw a dramatic effect in a small amount of patients with a variety of conditions," Dr. Martin N. Bomalaski, of the University of Michigan in Ann Arbor, said in a news release.

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"This is one of those strange paradoxes where the effects of an insomnia drug seem to have the opposite effect for patients who have paralysis or neurologic conditions," added co-investigator Dr. Mark Peterson of the University of Michigan Institute for Healthcare Policy and Innovation and Neuroscience Graduate Program.

The study appeared online June 26 in JAMA Neurology.

The researchers identified 67 reports for full review. These studies included a total of 551 patients but only 11 of them had more than 10 participants.

The review is “limited because of the preponderance and heterogeneity of low-level evidence, such as case reports and case series. Thus, our understanding relies heavily on the small number of well-powered controlled trials,” the authors caution.

Thirty-one studies used zolpidem to treat movement disorders, 22 for disorders of consciousness, and 14 for other neurologic conditions, including stroke, traumatic brain injury, encephalopathy, and dementia. The studies included 28 case reports, eight case series, 13 single-patient interventional trials, nine pretest and posttest trials, nine randomized clinical trials and five crossover studies.

In these trials, the effects of zolpidem were “wide ranging,” including improvement on the JFK Coma Recovery Scale-Revised, the Unified Parkinson Disease Rating Scale, and the Burke-Fahn-Marsden Dystonia Rating Scale, the authors report.

The effects tended to last only for the duration of the drug treatment, typically one to four hours, but were repeatable during extended use without increased tolerance, the authors say.

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Some patients with disorders of consciousness (DOCs) improved to a minimally conscious state, and “multiple studies also demonstrated correlations between clinical improvement and changes on functional neuroimaging,” the authors say. “For patients who responded to zolpidem, the effects were often significant, restoring consciousness in those with long-term DOCs or resolving symptoms of akinesia and rigidity in a patient with Parkinson disease,” they write.

But zolpidem only helped a minority of patients. The response rate in the articles reviewed was between 5% and 7% for patients with disorders of consciousness, and up to 24% or higher for patients with movement disorders. Sedation was the most common side effect.

“The underlying characteristics that distinguish responders from nonresponders have not been clearly elucidated. The answer likely lies in which brain areas have impaired function due to acquired brain injury rather than as the result of demographic or mechanistic factors,” the authors write.

"This kind of report brings up more questions than answers, although something like this is really foundational to guide a larger clinical trial," Dr. Peterson said in the news release.

"We still need to learn much more in order to answer the question about whether we should be using this in our clinical practice,” added Dr. Bomalaski.

“The next step in clinical research,” they conclude in their article, “would be to conduct large RCTs using validated outcome measures, such as the JFK Coma Recovery Scale-Revised for DOCs and the Burke-Fahn-Marsden Dystonia Rating Scale for dystonia, in addition to functional neuroimaging to correlate clinical observations to neuromodulation. These investigations are essential to better understand zolpidem’s safety, efficacy, and tolerability in treating these neurologic disorders.”

The study had no commercial funding and the authors have disclosed no relevant conflicts of interest.

SOURCE: http://bit.ly/2tlZ6Vt

JAMA Neurol 2017.

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