Clinical and imaging evidence of Zolpidem effect in hypoxic encephalopathy

A new study reported that zolpidem, a drug normally used to treat insomnia, temporarily improved brain function in a patient suffering from akinetic mutism, a condition in which the person is alert but cannot speak or move.

The patient was able to communicate, walk, and eat without assistance after receiving the drug for a bout of insomnia. The study was published in the March 2007 issue of Annals of Neurology, the official journal of the American Neurological Association.

Led by Christine Brefel-Courbon, M.D., of the University Hospital in Toulouse, France, researchers conducted a study of a 48 year-old woman who developed akinetic mutism due to oxygen deprivation to her brain following an attempted suicide by hanging. The patient was totally dependent, unable to speak or walk, and was using a feeding tube for nourishment, although she was able to understand single words. Two years after the suicide attempt, she was given zolpidem for a bout of insomnia; 20 minutes later, she was able to communicate to her family, eat by herself, and move. These effects lasted for up to three hours. After systematically withdrawing all of her medications one by one, it was concluded that the positive effect was due to zolpidem. "This phenomenon was so reproducible that caregivers used to give her up to three tablets each day without sleepiness as 'side effect,'" the authors state.

The researchers systematically assessed the effect of zolpidem on motor and cognitive function and explored its effect on brain activity using positron emission tomography (PET) scans. They administered motor tests such as finger tapping and walking, and language tests such as spontaneous speech, word repetition, and object naming. They also conducted brain imaging studies to assess brain metabolism and cognitive activation using PET scans. All of these were conducted with both zolpidem and a placebo in a randomized, double-blind study.

The results showed that after receiving zolpidem, the patient was able to stand up and walk, repeat words and sentences, read words, and name objects, although she was not able to speak spontaneously. Administration of the drug increased brain metabolism, and PET scans also showed improvement in cerebral areas involved in motivational processing.

Although previous studies have shown the positive effect of zolpidem on catatonic conditions, the authors state, "To our knowledge, this is the first study assessing the impact of zolpidem of post-anoxic brain injury using the modern methodological standards of clinical pharmacology." The authors demonstrated increased brain activity in the frontal cortex, which is associated with higher cognitive performances, with zolpidem. They suggest that the mechanism may be due to an activation of neural circuits in the brain that control movement and verbal expression, but that the lesions that occurred due to oxygen deprivation may have been too severe to allow spontaneous speech. They conclude that single patient trials can be a logical approach to identifying potentially beneficial drugs, especially in the case of rare or orphan diseases.