Sleeping pills offer wake-up call to vegetative patients Drug could overcome brain shutdown...

news@nature.com ^ | 23 May 2006 | Michael Hopkin

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Published online: 23 May 2006; | doi:10.1038/news060522-9

Sleeping pills offer wake-up call to vegetative patients

Drug could overcome brain shutdown caused by trauma.

Michael Hopkin

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," 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 effect is amazing to say the least.  Ralf Clauss, Royal Surrey County Hospital, UK

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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References

1. Clauss R.&

   Nel W. NeuroRehabilitation, 21. 23 - 28 (2006).

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[A CA Guy]

That is great news.

Will it work for Senate Republicans?

[billorites]

Posting this article isn't a crime.

But, it oughta be...

[tacticalogic]

It says "comatose", not "inchordate".

[Ichneumon]

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.

Cautionary tale: The movie "Awakenings" was based on true events which took place in 1969. A doctor discovered that a new (at the time) drug, L-Dopa, would wake patients who had been catatonic for years. They were fully conscious and could carry on conversations, etc. The drug was horrendously expensive, but because it worked miracles, the hospital found ways to fund the doses.

Then they started noticing that as time went by it took more and more of the drug to be effective...

Eventually, no safe dosage of the drug would work any longer, and the patients tragically faded back into catatonic states, for the rest of their lives.

[Revel]

It would have been great to give this drug to Terri Schindler Schiavo.

[MotleyGirl70]

That is great news.

Will it work for Senate Republicans?

I'll BUMP to that.

[GOPJ]

Thanks for the ping.

[syriacus]

Very interesting article! Thanks for the ping!

[syriacus]

Sleeping pill wakes men in vegetative state Sarah Boseley, health editor Tuesday May 23, 2006 The Guardian

Patient N "was constantly uttering random screams". After he was given the drug, the screaming stopped, and he started watching television and reacting to his family.

[steve-b]

Drug could overcome brain shutdown

Somebody put some of this stuff in the Capitol water coolers, stat.

[GOPJ]

Will it work for Senate Republicans?

Good one.

[supercat]

Eventually, no safe dosage of the drug would work any longer, and the patients tragically faded back into catatonic states, for the rest of their lives.

That a drug appears to impart awareness to a person who would otherwise appear to be PVS does not mean that it should necessarily be used to continuously impart conciousness. At minimum, however, I would think short-term use of the drug could be very useful in diagnosing a person's condition.

It may well be that a person's condition is such that there is no known therapy that would provide long-term improvement. On the other hand, if a drug provides short-term improvement, that would suggest that the prognosis for long-term improvement should be excellent (since it implies that the necessary parts of the brain are in "operable" condition and will work if properly stimulated, even if the proper means of stimulation are not yet known).

[Coleus]

CAN UNCONSCIOUS PATIENTS WAKE UP?

In the wake of the discovery (reported in last week's BioEdge) that a brain-damaged woman in the UK in a persistent vegetative state was responding to stimuli, other stories about recoveries from irreversible comas are emerging in the press. While many doctors are sceptical, the possibility that some therapies may restore some consciousness in some cases threatens to overthrow a consensus on how to deal with patients languishing in hospitals and nursing homes.

Bioethicist Joseph Fins, of Cornell's Weill Medical College, says that ever since the Karen Ann Quinlan case in the US in the 1970s, doctors have been abandoning brain-damaged patients too readily. As a result, fewer patients improve and the statistics get worse. Then families and doctors give up and researchers stop pursing new treatments. It becomes a vicious circle which Fins dubs therapeutic nihilism. "We've spent a long time allowing people to die," he says. Maybe they deserve more intellectual, diagnostic and therapeutic engagement than we have acknowledged."   One simple therapy which has produced remarkable results comes from South Africa: a sleeping pill. A family doctor near Johannesburg discovered that when some severely brain-damaged patients are given zolpidem they emerge from their comas and begin to communicate. No one understands why, but it appears that the damaged brain cells are not dead, in some cases at least, but only hibernating. The drug may wake them up.

A journalist for the UK Guardian met several patients who emerge from a persistent vegetative state after taking zolpidem. The degree of recovery varies, and lasts only about two and a quarter hours, but some of the recoveries appear remarkable. Papers describing what happens have been published in the journals NeuroRehabilitation and the New England Journal of Medicine and a British company, ReGen Therapeutics, is carrying out clinical trials.   Another therapy is electrical stimulation of the brain. An American doctor, Edwin Cooper, claims that people given electrical stimulation emerge from comas more quickly and regain functions more quickly than if they are given only traditional treatment. His work has not attracted much attention in the US ­ and was even denounced by the recently deceased expert witness in the Terri Schiavo case, Ronald Cranford, as "junk science".

However, in Japan, electrical stimulation is far more common. Doctors there implant electrodes directly into the spine. The results are not spectacular, but they are significant. About 40% of patients move from a persistent vegetative state to a minimally conscious state. Small as this may seem, relatives regard it as a blessing.   Even if these treatments are only experimental, if they can be verified, their implications for end-of-life treatment are enormous. If a persistent vegetative state is no longer a hopeless and irreversible condition, it will become more difficult to justify withdrawing life support from patients. ~ Wired, Sept 6; Guardian, Sept 12   

[jwalsh07]

Pretty amazing stuff. A hit of ambien and voila!

[8mmMauser]

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[The Wizard]

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[The Wizard]

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[Apple Blossom]

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[bmwcyle]

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