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Sleeping pills offer wake-up call to vegetative patients

May 23, 2006 By Michael Hopkin This article courtesy of Nature News.

Drug could overcome brain shutdown caused by trauma.

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Clinical researchers have discovered that they can rouse semi-comatose patients by giving them, bizarrely, a common sleeping drug. If more wide-ranging tests are successful, the drug could become the first effective treatment for 'persistent vegetative state', the condition at the centre of the US legal battle over sufferer Terri Schiavo last year.

British and South African doctors have reported the cases of three semi-comatose patients who were revived for several hours at a time by zolpidem, marketed to millions of insomniacs under the brand name Ambien. The drug allows the semi-comatose patients to talk with friends and family for several hours before the effect wears off, they report in the journal NeuroRehabilitation1.

The patients, two of whom suffered severe head injuries in motor accidents and a third who was left brain damaged by a near-drowning incident, have been taking the pills every day for several years, with no severe side effects.

The effect is amazing to say the least.
Ralf Clauss,
Royal Surrey County Hospital, UK
"The effect is amazing to say the least," says Ralf Clauss of the Royal Surrey County Hospital in Guildford, UK, who discovered it along with his colleague Wally Nel of the Family Practice in Pollack Park, Springs, South Africa. "They can interact, make jokes and speak on the phone." One of them even mastered catching a baseball.

The treatment was a chance discovery, Clauss says. He recalls that one of the vegitative patients was experiencing restless movements, and that Nel was trying to calm them with the use of a sleeping pill. "Lo and behold, he woke up 15 minutes later," says Clauss. "And so now we're using a sleeping drug to wake people up in the morning."

Drowsy days

It seems like the ultimate paradox. But Clauss theorizes that the brain processes that help to govern sleep may be the same as those that malfunction and shut the brain down as a result of trauma. The drug is still acting as a sleeping pill in these patients too, he notes: if the dose is high, the patients become conscious but sleepy.

The effect seems to hinge on the GABA system, says Clauss. Many brain cells possess receptors on their surfaces that bind to a molecular messenger, or neurotransmitter, called GABA; and this binding can, amongst other things, promote sleep. Ordinarily, zolpidem boosts the binding process, helping weary insomniacs to drift off.

But in severely damaged brains, perhaps this system can become oversensitized, Clauss suspects. A trauma such as a blow to the head can kill off swathes of brain cells. Perhaps it also makes many of the remaining brain cells supersensitive to GABA. This would cause them to shut down upon the slightest hint of binding, which would act as a defence mechanism to prevent the body from being over-stressed and causing further cell death.

If too much of the brain shuts down in this way, the result would be a persistent vegetative state, a so-called 'waking coma' in which the patient can often sit and breathe unaided, but seems unaware of anything or anyone around them. Such a state may be the result of the brain trying to protect itself, but not in a very useful way.

Clauss wonders whether zolpidem may change the shape of supersensitized GABA receptors, making GABA less likely to shut these cells down. This could turn off the body's self-defence mechanism and allow the patient to wake.

Waking hours

The drug company ReGen Therapeutics in London, UK, is now attempting to formulate the drug specifically for this purpose. Clauss says that he then hopes to proceed with clinical trials of the treatment. It is unclear how well the drug would work, or for how long, on different patients.

He says that there is no reason why the drug cannot be provided as a slow-release formula, allowing patients to remain permanently aware. But the long-term effects of such a treatment are completely unknown.

The remedy could potentially offer hope to patients with other forms of neurological damage, such as those suffering from stroke, Parkinson's disease, supranuclear palsy or some forms of deafness, Clauss hopes. But he adds that the success rate for one-off brain injuries such as stroke would be greater than for progressive disorders in which brain damage accrues, such as dementia.

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  1. Clauss R.& Nel W. NeuroRehabilitation, 21. 23 - 28 (2006).


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