A drug used to treat insomnia has paradoxically helped temporarily rouse three men who were each in a vegetative state following motor accidents, researchers claim. They believe that zolpidem (marketed as Ambien) activates dormant cells in the brain.

But experts caution that the patients may not have been in a permanent vegetative state (PVS), and that the men may simply have shown signs of natural recovery.

The initial discovery that zolpidem could benefit patients of severe brain trauma came about accidentally, according to Ralf Clauss, who led the study at the Royal Surrey County Hospital in Guildford, UK. He and colleagues reported in 2000 that the drug seemed to help restore partial consciousness, at least temporarily.

Their new study details the effects of the drug in three patients, all of whom have been in a PVS for at least three years. People in this state may have regular sleep cycles but do not show detectable awareness. The men received daily doses of zolpidem for up to 6 years.


Meaningful interaction

Before treatment with the drug, Patient L did not respond to any commands and showed no signs of language comprehension. According to Clauss, after taking his first, 10 milligram dose of zolpidem the patient could meaningfully interact with family, friends and strangers. He could name his favourite rugby player and make simple calculations.

The effects of the drug seemed to last for approximately 4 hours, after which Patient L would relapse into the vegetative state.

Patient N, who had been in a vegetative state for three years following a motor vehicle accident, showed no signs of language comprehension and was constantly screaming. With the drug he stopped screaming and appeared to react appropriately to scenes on television, laughing at funny moments.

Before taking zolpidem, Patient N scored 6 out of a possible 15 points on the Glasgow Coma Scale, a measure of responsiveness. With the medication, his score improved to 10. A coma score of 13 or higher correlates with mild brain injury while a score of 8 or less is generally considered severe brain injury.

The third man, Patient G, showed no response to language prior to drug treatment but could count to five after receiving the medication, the researchers write. His score on the Glasgow Coma Scale improved temporarily from 9 to 14 points.

All three patients have received daily doses of the drug since the study began.

Misdiagnosis?

Clauss and his colleagues have applied for a usage patent of zolpidem in brain damage. He says that drugs such as zolpidem, manufactured by Sanofi-Aventis, activate receptors for the neurotransmitter gamma aminobutyric acid (GABA) in the brain.

According to the researchers, brain injury may alter GABA receptors, causing regions of the brain to remain dormant. They speculate that zolpidem could possibly, temporarily, reverse this change.

Other experts stress, however, that people are sometimes misdiagnosed as being in a permanent vegetative state. Mike Barnes, professor of neurological rehabilitation at the Hunters Moor centre in Newcastle, told the BBC: “A diagnosis of PVS means the patient should not wake up and respond.”

An article published in the British Medical Journal in 1996 (vol 313, p 13) found that 43% of 40 patients were considered misdiagnosed with the condition. Only 13% of the patients remained vegetative, the study reported.

Journal reference: NeuroRehabilitation (vol 21, p 23)