Insomnia Drug Can Improve Brain Function

Caroline Cassels

March 13, 2007

March 13, 2007 — A new study reports that the insomnia drug zolpidem (Ambien, Sanofi Aventis) temporarily improved brain function in an adult patient with akinetic mutism caused by anoxia.

The 48-year-old woman suffered akinetic mutism related to a postanoxic encephalopathy a few days after a suicide attempt by hanging.

Two years later, she was prescribed zolpidem to treat a bout of insomnia. Within 20 minutes of receiving a 10-mg dose of the drug, the subject, who had been unable to speak or walk and was fed by a gastrostomy, was able to communicate, walk, and eat without assistance. These effects lasted for up to 3 hours.

"This phenomenon was so reproducible that caregivers used to give her up to 3 tablets each day without sleepiness as a 'side effect,' " the authors note.

The study is published online March 13, 2007 in Annals of Neurology.

Motor Performance Markedly Improved

To evaluate the drug's efficacy on motor and cognitive function and explore its effect on brain activity, researchers, led by Christine Brefel-Courbon, MD, from the University Hospital in Toulouse, France, conducted a crossover trial in the 48-year-old patient that was randomized, placebo controlled, and double-blind.

The schedule consisted of 6 modules of either drug or placebo separated by an interval of 24 hours. During each module, the patient received 20 mg of zolpidem or placebo through her gastrostomy catheter.

In the first 2 modules — 1 with placebo and 1 with zolpidem — a blinded clinician administered motor and language tests at baseline and 30 minutes after drug administration.

In the final 4 modules, the patient underwent 2 brain-imaging studies, a brain metabolism measurement using the 18-fluorodeoxyglucose positron emission tomography (FDG-PET) method and a cognitive activation study using the H2 15O PET method.

According to the authors, zolpidem markedly improved motor performance, enabling the patient to stand up and to walk. At baseline and after placebo, a complete mutism coexisted with relative sparing of auditory and visual comprehension for single words.

Although spontaneous language remained absent after receiving zolpidem, the patient was able to repeat single words and sentences aloud, read words, and name and/or repeat the names of objects.

Utility of Single-Patient Studies

Baseline findings on FDG-PET imaging showed a decrease of brain metabolism in large, bilateral rostral/subcortical territories, especially in the medial and lateral frontal cortex and thalamic areas.

However, after zolpidem therapy, cerebral metabolism increased in the postrolandic territories by 30% (and limited portions of the lateral frontal cortex) and, to a lesser extent, in anterior cingulate, medial, and orbitofrontal cortices and thalami (by 25%), the authors report.

During the H2 15O PET session performed under placebo, the naming task did not induce any significant change in regional cerebral blood flow (rCBF), and patient performance was poor.

In contrast, with zolpidem therapy, there was a similar improvement in the patient's naming/repetition performance. An rCBF image analysis showed a drug-induced activation mainly localized in the anterior cingulate and orbitofrontal cortices.

Although previous studies have shown the positive effect of zolpidem oncatatonic conditions, the authors state that "to our knowledge this is the first study assessing the impact of zolpidem on postanoxic brain injury using modern standards of clinical pharmacology."

The authors also note that single-patient drug trials such as this can provide a way to identify uses for drugs, especially in the case of rare or orphan diseases.

Ann Neurol. Published online March 13, 2007.

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