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Sleeping pills offer wake-up call to vegetative patients Drug could overcome brain shutdown...
news@nature.com ^ | 23 May 2006 | Michael Hopkin

Posted on 05/23/2006 5:14:12 PM PDT by neverdem

news@nature.com - the best science journalism on the web Close window



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.

Visit our newsblog to read and post comments about this story.

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References

  1. Clauss R.&

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

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Story from news@nature.com:
http://news.nature.com//news/2006/060522/060522-9.html

Nature Publishing Group, publisher of Nature, and other science journals and reference works © 2006 Nature Publishing Group | Privacy policy


TOPICS: Health/Medicine
KEYWORDS: ambien; health; medicine; pvs; vegetativestate; zolpidem
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To: neverdem; Freee-dame

This makes so much sense to me, it gives me chills.

Just as children are prescribed a stimulant to calm them down (but that's a topic for another thread,please) this medication calms the brain enough for it to rouse to an awake state. How wonderful!

Modern medicine "discovered" the value of putting patients into comas for therapeutic reasons, but did not clue in that nature already had the same mechanism built in to our DNA.


21 posted on 10/15/2006 5:26:30 AM PDT by maica (9/11 was not “the day everything changed”, but the day that revealed how much had already changed.)
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To: neverdem

I posted on another thread on this topic of using Ambian.

I am taking the adult son (basal ganglia severe brain damage) aka Severe Cerebral Palsy for his check up and going to ask for a sample of Ambian.

The son is overly aware mentally but the severe flailing, tongue thrust and spacticity that has not responded to other treatments (we have tried it all) may benefit from ambian. Worth a try.
His biggest problem is when he gets jazzed about his schedule/events he goes into severe CP movement and lung spasms.
He takes a cocktail of meds now but if to excited he can over ride the effects of the meds.
I have gotten to the point of not telling him when certain events are untill we get there to prevent all the excess movements/spasms.
He went last night to take pics with his Labs with Santa and we had to sit and wait an hour before to allow him to calm enough before we did the pics.
Luckily the 4-H Leader has known us for decades and was very helpful in accomadating him.
I noticed the date of your post May 23. That is his birthdate, hope it is a good sign. : )


22 posted on 11/16/2006 10:13:08 AM PST by Global2010
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To: Global2010

Good luck!


23 posted on 11/16/2006 10:25:10 AM PST by neverdem (May you be in heaven a half hour before the devil knows that you're dead.)
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To: neverdem

Had his first one day dose.
It was like the one glass of wine we all have and relax.

Wow....give you the update after 14days...


24 posted on 11/16/2006 10:04:52 PM PST by Global2010
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To: neverdem

OK Talked to him this morning.
It had the effect of euphoria.
Like a couple glasses of wine.
He did physical relax as in the spacticity let go.
Soooo he decided he would take a dose like for tommarrow night when he goes to see Howie Mandel.
He is looking great this morning as in less thrashing/flailing around. sooooo perhaps a post dose effect.
He loved it, the ability to relax and feel euphoria.


25 posted on 11/17/2006 9:47:20 AM PST by Global2010
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Sleeping pill Zolpidem awakens girl from coma

A girl who has spent six years in a coma is showing signs of life after taking a sleeping pill.

 
Amy Pickard: Sleeping pill awakens girl from six-year coma
Amy Pickard before she fell unconscious in 2001 and with her mother Thelma while in hospital

Amy Pickard, 23, had lain in her bed, unable to eat or breathe for herself since falling unconscious in 2001. But after being enrolled in a study of the side-effects of the sleeping pill Zolpidem, her eyes have begun to sparkle and she has even managed to stand.  Amy's mother, Thelma Pickard, 54, has visited her every day at the Raphael Medical Centre in Tonbridge, Kent, and claims that she can see her "feisty and determined" daughter fighting her way to recovery.

She reacts to strong-tasting foods, can breathe unaided, focus on objects in her room and is beginning to formulate words."When she takes the pill, I see her face relax and the old sparkle return to her eyes. It truly is remarkable," said Mrs Pickard. Amy, who is the subject of a BBC1 documentary The Waking Pill to be broadcast tonight, was 17 and studying for her A-Levels at Filsham Valley School in East Sussex when she was persuaded to inject heroin by her then boyfriend.

She is one of 360 people taking part in a worldwide trial of Zolpidem as a treatment for people in comas. Sixty per cent of patients taking part in the study have started showing signs of life. The drug's side-effects were first discovered after a 24-year-old South African cyclist suffered a serious brain injury after being hit by a lorry in 1994. Doctors told his parents that he would never regain consciousness.  Five years after his accident, nurses noticed he was involuntarily grabbing at his mattress and gave him Zolpidem to help him sleep more deeply. Instead, just 25 minutes later, he sat up in bed and said: "Hello, mummy." The British firm ReGen Therapeutics began a trial and, as one of those involved, Amy's mother was flown to South Africa to meet other patients who had tried it.

 
Amy Pickard and her mother Thelma
Amy as she is now, fighting her way to recovery

She said: "I've had so many disappointments in my life, so I didn't set my expectations too high. When I came back from South Africa, I was exhausted, but the hope in my heart was intense. "But the more I saw, the more I heard and the more I experienced, the more I realised Amy must try this new treatment." Barely four weeks after taking her first pill, Amy, who has an older brother David, 27, is making good progress.

Doctors have warned Mrs Pickard it could take months for a breakthrough, but she believes her daughter is already on the road to recovery. "When I look at her now I can see the old Amy coming through, fighting to get out. It's a day-to-day waiting game to see what will happen next, but I just know she's going to speak any day," she said. "Every day she takes the tablet, it gives me more and more hope. My life is better now than it's ever been over the past six years." The story echoes the plot of the film Awakenings, which stars Robert de Niro and Robin Williams. It is based on real events, in which a research physician uses an experimental drug to "awaken" the catatonic victims of a rare sleeping sickness.

Could a Sleeping Pill 'Wake Up' Coma Patients?
Minimally Conscious Woman Becomes More Alert After Ambien, Researchers Report

For many of us, it's a quick and easy way to help us fall asleep. But for a few patients with brain damage, taking zolpidem -- a drug commonly known by the brand name Ambien -- may lead to increased alertness, as well as improved language and motor skills, French researchers report.  A study, which appears in the current issue of Annals of Neurology, involved only a single patient: a woman who had suffered brain injury when a suicide attempt led to oxygen being cut off to her brain.

This left her with a condition known as akinetic mutism. She could see and otherwise sense everything going on around her, but she was unable to communicate, feed herself or walk.  The patient, however, still experienced insomnia. This led doctors to add a dose of zolpidem to her usual treatment.  That's when things got interesting.  "Twenty minutes later, her family noticed surprising signs of arousal," the authors write. "She became able to communicate to her family, to eat without [swallowing] troubles, and to move alone in her bed."  The researchers say this welcome "side effect" is exceedingly rare, but this is not the first time it has happened. Neurologists say the drug at least presents caregivers with a long-shot option -- and could possibly lead to future treatments for these patients.

'Transient Awakenings' With Sleeping Pill

While a single such case could be chalked up to a one-shot medical mystery, such effects have been seen before in other brain-damaged patients taking the drug.  In July, ABC News' "Good Morning America" reported a similar recovery of consciousness seen in George Melendez, a young Texan who had suffered brain damage in a car wreck in 1998. His injury made it impossible for him to move or communicate with his family.   The surprise came 10 minutes after he received his first dose of Ambien.  "I noticed there was no sound coming out of George," said Melendez's mother, Pat Flores, to ABC News correspondent Mike von Fremd. "And I looked over to the next bed and said, 'Hey, George.' And he comes and says, 'What?' And that was the first time he had spoken. I tugged at my husband and said, 'Look, look he is talking.'"   Neurologists say that these "miracle" awakenings are not unheard of.

"There is sort of a precedent for that; there are articles in the literature that show this," said Dr. Wendy Wright, assistant professor of neurology and neurosurgery at Emory University Hospital in Atlanta. "There are patients who have even been in vegetative states that doctors have given Ambien to and have had transient awakenings."  "It is known that these patients who have minimal consciousness can have a paradoxical reaction to things that make other people fall asleep."  In fact, as Dr. Ausim Azizi, professor of neurology at Temple University School of Medicine in Philadelphia, points out, many doctors already look to this and other drugs routinely to give their patients a long-shot chance at arousal.  "In practice, it is being used already," he said. "In my ICU, we have had 400 people with comas coming in. We'll try a bunch of things, including different drugs. Sometimes they work, sometimes they don't."

Reasons for Recovery Remain Mysterious

Though the exact way that the drug works for these patients is still not entirely clear, researchers say the effects could be linked to Ambien triggering a cascade of events in the brain known as the GABA pathway.  In normal brains, this causes drowsiness. In brains in which the chemical balance has been somehow disturbed, triggering this cascade could have the opposite effect, bringing alertness and increased brain function.  Azizi says that the seemingly counterintuitive approach of giving minimally conscious patients a drug that would cause normal people to feel drowsy is actually backed by a respectable amount of experience.

"This is similar to what we think is happening in patients with ADHD [attention deficit hyperactivity disorder]," he said. "We give them a stimulant, such as Ritalin, and it has a paradoxical effect, actually calming them down."  Emory's Wright says that this knowledge could perhaps lead to future treatment strategies for brain-damaged patients.   "There are plenty of other medicines out there that are GABA agonists," she said. "Now maybe these could be tried as well, and tried earlier in treatment, to see if there is an effect."

But why does it work for only some patients?  To understand this, Azizi says that the brain can be thought of like a computer. The "hardware" is the brain's structure, an intricate network of internal connections of neurons and nerves that form the circuitry of the brain. The other component he terms the "software," the chemical and electrical impulses that race through this tangled web.  If the damage to the brain is a disruption of the "software," the structural circuitry of the brain may be preserved to the extent that a bit of a "reboot" -- such as that seen with a dose of Ambien -- may help restore the balance needed for the patient to wake up or communicate.   However, if the "hardware" is damaged, if the circuits themselves have been destroyed, then there is less of a chance that the drug will be able to restore any degree of normal function.  "The stipulation is that structurally, the brain cannot be damaged," Azizi said.

Drug Worth a Shot

The fact that no two brain injuries are exactly alike means that it is unlikely that zolpidem will ever be viewed as a cure-all for every minimally conscious patient.  "It's not going to work for everybody," Wright said. "But under a doctor's supervision, this might be something worth trying."  Considering the possible benefits, this shot at a miracle may give family members a small ray of hope.  "They should talk to their doctor and say, 'Doc, have you tried this on my loved one?'" Azizi said. "There are relatively few side effects, and it may be beneficial."

Video

26 posted on 03/09/2008 7:59:23 PM PDT by Coleus (Abortion and Euthanasia, Don't Democrats just kill ya?)
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