Drug info - Ambien (Zolpidem) 'reverses' vegetative state

[BlueMystic]

http://news.bbc.cohttp://news.bbc.co...th/5008744.stm

Pill 'reverses' vegetative state
BBC News
5/23/2006


A sleeping pill can temporarily revive people in a permanent vegetative state to the point where they can have conversations, a study finds.

Zolpidem is usually used to treat insomnia.

South African researchers, writing in the NeuroRehabilitation, looked at the effects on three patients of using the drug for up to six years.

But one expert in neurological rehabilitation said it was possible the patients had a different condition.



A person in a vegetative state will appear to be awake and may have their eyes open, but will show no awareness of their surroundings.

They will not be able to interact with other people, and will show no responses to sounds or things that happen around them.

But they will show signs of movement, and cycles of sleep and may be able to breathe on their own.

Response

Each of the three patients studied was given the drug every morning.

An improvement was seen within 20 minutes of taking the drug and wore off after four hours, when the patients restored to their permanent vegetative state.

Patient L had been in a vegetative state for three years, showing no response to touch and no reaction to his family.

After he was given Zolpidem, he was able to talk to them, answering simple questions.

Patient G was also able to answer simple questions and catch a basketball.

Patient N had been "constantly screaming", but stopped after being given the drug when he started watching TV and responding to his family.

Dr Ralf Clauss, now in the nuclear medicine department at the Royal Surrey Hospital was one of the researchers who carried out the study.

He told the BBC: "For every damaged area of the brain, there is a dormant area, which seems to be a sort of protective mechanism.

"The damaged tissue is dead, there's nothing you can do.

"But it's the dormant areas which 'wake up'."

Activity trigger

He said drugs like Zolpidem activate receptors for a chemical called GABA in nerve cells in the brain.

When brain damage occurs, these receptors appear to change shape, so they cannot behave as normal.

He said the drug appeared to cause the receptors in these dormant areas to change back to their normal shape, triggering nerve cell activity.

Dr Clauss added: "We are carrying out further research. The next step is to get rid of the sleepiness effect of the drug."

Mike Barnes, professor of neurological rehabilitation at the Hunters Moor centre in Newcastle, said it was possible that the patients had not had "true" PVS.

"A diagnosis of PVS means the patient should not wake up and respond."

He said a study carried out by specialists 10 years ago had shown that up to 45% of patients diagnosed with PVS actually had a range of different conditions, from which they could wake up.

Professor Barnes added: "This drug could be unmasking a condition from which people are able to wake up temporarily.

"But if they did have PVS, it would be a remarkable finding, and certainly worth further research."

Reputation Comments on this post:

Very interesting

[Micklemouse]

An update, again from the BBC

http://news.bbc.co.uk/1/hi/health/6164716.stm

Family right-to-die plea rejected

Zolpidem works on nerve cells in the brain

A woman in a vegetative state will be given a sleeping pill which may "wake her up" against her family's wishes. The 53-year-old, who has not been named, will be given zolpidem which early research has shown can bring people out of a vegetative state.
Her family do not want the test to go ahead, preferring to let her die, as she may be left seriously disabled.
But Sir Mark Potter, head of the High Court's family division, ruled against their wishes earlier this month.
The drug proposal was put forward by Laurence Oates, the outgoing Official Solicitor, who suggested that zolpidem be prescribed, the Guardian newspaper reported.
He [the Official Solicitor] believes that no stone should be left unturned in trying to save life


Department for Constitutional Affairs spokesman


It is normally used to help insomnia but has been cited in a number of cases where it has caused patients in a persistent vegetative state (PVS) to wake up.
An improvement was seen within 20 minutes of taking the drug and wore off after four hours, when the patients restored to their permanent vegetative state.
Professor Keith Andrews, who looks after severely brain-damaged patients at London's Royal Hospital for Neuro-disability, said the drug had not worked on the patients he had tried it on.
And he added: "I personally don't think it will work in this case."
But a spokesman for the Department for Constitutional Affairs said: "It is a very difficult situation.
"The Official Solicitor, who represents the woman, came to a view that was opposite to the family.
"He accepts that there are incredibly sensitive issues that need to be addressed with this family and the woman itself.
"But he also takes the view that there are other issues for other patients in this situation.
"He believes that no stone should be left unturned in trying to save life."
Drug
It is not known when the drug will be given to the woman, although the judgement only allows doctors to give a three-day course of the drug and they have been told they must stop if the woman starts to suffer.
The woman was diagnosed as PVS after she suffered a brain haemorrhage while on holiday in August 2003.
The newspaper said her family wanted her to die with dignity and not live with the disabilities zolpidem might cause.
They are said to be in favour of removing the artificial feeding tube to let her die.
It is not the first time a PVS patient has caused ethical problems.
In 1993, the Law Lords ruled that Hillsborough stadium disaster victim Tony Bland could have his feeding tube removed.
The 22-year-old was crushed and his brain starved of oxygen during the FA Cup semi-final disaster in April 1989, when 95 people died.
For nearly four years he was in a persistent vegetative state.
Charges
Doctors at Airedale Hospital in Steeton, West Yorkshire, insisted he would never recover.
His parents fought a legal battle that went to the High Court, the Court of Appeal and finally the House of Lords for the right to lawfully withdraw their son's life-sustaining artificial feeding tube.
The House of Lords ruled that doctors could stop feeding Mr Bland, enabling the hospital to remove the tube without facing charges of murder.
Timothy James, a medical law expert at the University of Central England, said the Bland case established a precedent enabling treatment to be withdrawn.
But he added if doctors could wake up someone they would then be able to ask them what they want.
"It becomes their own decision."
And Dignity in Dying chief executive Deborah Annetts said the decision was deeply troubling as "the human rights of the woman at the centre of this case are being ignored, and she is effectively being treated as a guinea pig".

[Nagognog2]

Where's John Cleese when you need him?

[Jatelka]

Can any SWIY find these PDF's?

http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16720934

http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum

PS: Is it just SWIJ or is this case horrifying? Both the partner and the womans mother are clear that she would not want to exist in the state she is existing currently. The official solicitor suggests that this be tried, despite the fact that this womans loved ones are in complete opposition to it? Come on! How is this just?

[Nagognog2]

It 'SOUNDS' like attempted homicide from here as well, Jatelka.

"He's in a coma from the auto accident." "Oh! He's always borrowing money - let him die." "Okay."

[snapper]

Still, this property of ambien is interesting. It is known for amnesic behavior already in some that take it, so could it be that this amnesic behavior is awakening a 'resting' part of the brain. Is this another version of self, or some manifestation of the subconscious? Sure, the specific case aforementioned is disturbing and wrong, but this property of the drug is unique and raises many questions. Maybe a confirmation that people have multiple or alternative personalities or behaviors ?

[Micklemouse]

More likely a confirmation of the vegetative state being an extreme state of shock. A Certain Mouse has seen people in catatonic states respond to rapid sedation (intramuscular lorazepam generally, but also haloperidol & clopixol acuphase in small doses). The theory being that they are in such a heightened state of agitation that they cannot actually move. If you read the original article zolpidem was initially used to calm someone who was highly agitated whilst still in a pvs. The drug calmed the agitation and also allowed limited cognition & verbal response to stimulus.

If this is a temporary condition that would allow the patient to state their true wishes, then all to the good. I think... Much could be learnt about what the patient is experiencing whilst in the pvs. There is no guarantee that there will be no brain damage if the person comes out of the pvs naturally. Families have been known to get it wrong when it comes to peoples wishes in these & similar cases. If the patient chooses to die, are we then looking at euthanasia?

It is an ethical minefield & no mistake.

[Nicaine]

Originally Posted by Micklemouse

More likely a confirmation of the vegetative state being an extreme state of shock. A Certain Mouse has seen people in catatonic states respond to rapid sedation (intramuscular lorazepam generally, but also haloperidol & clopixol acuphase in small doses). The theory being that they are in such a heightened state of agitation that they cannot actually move. If you read the original article zolpidem was initially used to calm someone who was highly agitated whilst still in a pvs. The drug calmed the agitation and also allowed limited cognition & verbal response to stimulus.

Interesting how zolpidem works extremely well (for SWIM) when desiring to "come down" in the middle of a strong stimulant high. Rather than producing drowsiness, it sedates and relaxes to an approximately "normal" mental and physiological state. Benzos like lorazepam or clonazepam don't do nearly as good a job. For this reason, SWIM is looking to acquire a backup supply of zolpidem (possibly at great expense/trouble) although he will be requesting his regular doctor to switch to Eszopiclone for sleep.

[Micklemouse]

Originally Posted by snapper

Still, this property of ambien is interesting. It is known for amnesic behavior already in some that take it, so could it be that this amnesic behavior is awakening a 'resting' part of the brain.

Looks like the experts agree, Snapper! A new article from the New Scientist

http://www.newscientist.com/article/...&nsref=dn11373

Sedative 'reactivates' damaged brains

• 16:55 13 March 2007
• NewScientist.com news service
• Debora MacKenzie

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• Sleep medication linked to bizarre behaviour
• 06 February 2007
• Sleeping pill may rouse coma patients
• 24 May 2006

A severely brain damaged woman has shown dramatic improvement in mental function after taking an insomnia drug, doctors say. The result may offer hope to millions of people living with serious brain damage.
It is the first reported case of the drug zolpidem helping an alert, non-comatose patient in this way.


The woman, from the south of France, was left unable to eat, speak or move unaided - although she did understand single words - after her brain was deprived of oxygen (hypoxia) during an attempted suicide by hanging.


After two years in this condition, she was given zolpidem (marketed as Ambien) following a bout of insomnia. Just 20 minutes later, as the drug hit her bloodstream, she was suddenly communicating with her family, eating and moving. Three hours later, as the drug waned, she returned to her usual state.
Circuit loops

The patient's carers started giving her three pills a day. Christine Brefel-Courbon and colleagues at Toulouse University Hospital tested the woman and found the drug allowed her to stand and walk, repeat and read words, and name objects, although she was still unable to speak spontaneously.


"The patient has been maintained on zolpidem every day," Brefel-Courbon told New Scientist. "Up to now, she has always improved," without any sign that she is losing sensitivity to the drug.
Meanwhile, PET scans, which measure the blood flow and metabolic rate in different areas of the brain, showed the drug boosted activity in brain regions which showed no activity without the drug. The team thinks zolpidem turned on specific "loops" of circuitry in the brain associated with motivation, movement and speech.


However, Ralf Clauss at Royal Surrey County Hospital in Guildford, UK, who has treated a number of such patients (see Sleeping pill may rouse coma patients), thinks the drug's effect may be more generalised throughout the brain.
"Silent" areas

"The work agrees with our findings," Clauss told New Scientist. PET scans of people with persistent brain damage often reveal areas that are "silent", or inactive, sometimes far from the actual damaged tissue.
"We find there's no obvious pattern to where these turn up," he says, but he suggests that they may be due to depletion of the neurotransmitter GABA. Zolpidem stimulates GABA receptors, which are active in different parts of the brain, not just the circuitry that triggers sleep.


Clauss's team has used zolpidem to successfully restore function in patients with hypoxia-induced brain damage resulting from stroke, injury and birth trauma. "We have one adult who suffered from birth trauma, who is now holding down a job for the first time after the drug improved their cognitive function," says Clauss.


Furthermore, New Scientist has learned that clinical trials are currently underway in South Africa by the drug company Regen Therapeutics, to see if the zolpidem can help other people with brain injuries.
Journal reference: Annals of Neurology (DOI: 10.1002/ana.21110)

[championventures]

This is quite the interesting story.