Zolpidem (Ambien/Stilnox) - The paradoxical "miracle" drug for brain damage

By infekt · Sep 1, 2008 · Updated Sep 1, 2008 · ·
  1. infekt
    I just saw this on 60 minutes and thought it was awesome.

    Watch the 60 minutes article:
    (Aug 28th 2008)

    "(CBS) This segment was originally broadcast on Nov. 25, 2007. It was updated on Aug. 28, 2008....

    ....What's even more remarkable is that another drug has recently been shown to have similar effects on some minimally conscious people. The case of George Melendez is perhaps the most dramatic of all. George suffered a brain injury when he crashed his car into a pond and nearly drowned. Weeks after the accident doctors told his mother, Pat Flores, her son would never get better.

    "What you see lying there in the bed is as good as it gets," Pat remembers of the diagnosis for her son. "That's as good as it gets. He's never gonna be able to do anything. He is a vegetable."

    George was in a minimally conscious state, but for years Pat was determined to reach him. She cared for him at home, while searching for new treatments.

    Pat believes George was always there, just unable to communicate.

    One night in 2002, unable to sleep because of his moaning, Pat gave George Ambien, a common sleeping pill used by millions of people.

    "I noticed the room got quiet and in my mind, I'm thinking, 'Wow, that pill's really good. It really knocked him out.' And when I looked over, instead of seeing a sleeping George, I saw a very much awake George with his eyes wide open and just scanning the room and looking," Pat remembers.

    For the first time in five years, Pat heard her son speak.

    The next day, sensing she was on the verge of a breakthrough, Pat gave George another dose of Ambien through his feeding tube. George's step-father taped the transformation.

    Within six minutes, George went from being unresponsive -- moaning and shaking -- to quiet, alert and answering questions.

    Asked what kind of questions she asked her son, Pat says, "If he knew where he was at. If he knew what had happened to him. If he was in pain."

    George told her he wasn't in pain. "He said no clearly, which that was a big relief," she recalls.

    Pat doesn't know why the Ambien works, but she's been giving it to George every day now for the last five years.

    60 Minutes helped arrange for George to see Dr. Schiff of Cornell. He performed exams to see if George's reaction to Ambien is real or just his mother’s wishful thinking.

    First, Dr. Schiff did a PET scan of George's brain off Ambien. The frontal lobe, the area responsible for behavior and language, was yellow, indicating greatly reduced brain activity.

    The next day, after he was given Ambien, George was put back in the scanner. The frontal lobe, seen earlier in yellow, was now bright red.

    "So we've just learned something here. Today's scan looks like it's about two or three times as intense, metabolically," Dr. Schiff observed. "That’s like a big deal. His brain is turned on, with this stuff."

    Asked if he has seen Ambien work on other patients, Dr. Schiff tells Cooper. "I have. And about a year and a half ago, I would've said, no. … And now, I've seen at least three cases."

    "And do you think there are more people out there who could benefit?" Cooper asks.

    "I think you're gonna find a subset of patients who respond to it," Schiff says

    (CBS) Other Ambien "awakenings" have been reported around the world, and the medical community is taking notice.

    There are several clinical trials of Ambien underway, but progress is slow, in part because minimally conscious people are scattered around the country in homes and nursing facilities, often far from research centers.

    Another obstacle to treating these people is that they're frequently misdiagnosed -- said to be in a vegetative state, a more severe condition, considered hopeless after the first year.

    "There have been some recent studies looking to see what the misdiagnosis rate was and they come up with a number of 40 percent," Dr. Schiff says.

    "So the number of patients who are said to be in a vegetative state, who may actually be in a minimally conscious state, could be as high as 40 percent, 20, 30, 40 percent?" Cooper asks.

    "In some context," Schiff says.

    Why were people misdiagnosed?

    Says Schiff, "You have to examine them repeatedly and at different times of the day, and sometimes just changing a patient’s posture, or giving them a tendon massage, may change their level sufficiently to elicit some response. So yeah, this is an evolving area of understanding."

    Dr. Adrian Owen, a neuroscientist from the Medical Research Council in Cambridge, England, thinks new technology may help diagnose these people earlier and more accurately than a bedside exam.

    Last year, he stunned the scientific world when he discovered that a woman who met the diagnostic criteria for being vegetative could actually respond to a command with her mind. To illustrate his study, Owen did a functional MRI scan of Cooper's brain to show how it activates when he imagines playing tennis.

    "Imagine you’re on the center court at Wimbledon hitting that ball left hand, right hand -- forehand, backhand, whatever," Owen instructed.

    Within minutes, the computer rendered a three-dimensional image of Cooper's brain.

    "This region across here is known as the motor cortex, this area has turned on in response to you imagining moving your arm," Owen observed. "I can show you what happened in our patient who’d been diagnosed as vegetative. The motor cortex is almost in exactly the same place as in your brain, and it activates in almost exactly the same way, when she imagines playing tennis."

    "What was that moment like, when you realized, 'Wait a minute. She’s actually responding to what I'm saying. She's in there?'" Cooper asks.

    "It was an absolutely stunning moment. Because we had no way of knowing beforehand that not only was she not vegetative, she was entirely consciously aware," Owen says.

    "Someone like Terri Schiavo would not have had brain activity that would have shown up in a functional MRI?" Cooper asks.

    "No. There are many differences between a patient like Terri Schiavo and the patient that we scanned. The first thing is the type of brain damage," Owen says.

    As for George Melendez, Dr. Schiff says he's progressed so much he's no longer minimally conscious, but severely disabled. Pat has increased George's Ambien dosage and is hopeful her son will continue to improve. But she remains a realist.

    "I'm not gonna get the old George back. I'm not that naïve and that much in denial, to think that I'm gonna get 100 percent of who George was at one time," Pat says. "But hopefully, it will be a George that will be able to live on his own and have a productive life."

    "That's what you want?" Cooper asks.

    "Yes," Pat replies.

    Asked if she thinks that's very possible, Pat tells Cooper, "It's possible.""


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  1. Expat98
    This is an older article, but very interesting and it hasn't been posted before. Also see this thread:

    Ambien (Zolpidem) 'reverses' vegetative state



    We have always been told there is no recovery from persistent vegetative state - doctors can only make a sufferer's last days as painless as possible. But is that really the truth? Across three continents, severely brain-damaged patients are awake and talking after taking ... a sleeping pill. And no one is more baffled than the GP who made the breakthrough. Reporter Steve Boggan witnesses these 'strange and wonderful' rebirths

    For three years, Riaan Bolton has lain motionless, his eyes open but unseeing. After a devastating car crash doctors said he would never again see or speak or hear. Now his mother, Johanna, dissolves a pill in a little water on a teaspoon and forces it gently into his mouth. Within half an hour, as if a switch has been flicked in his brain, Riaan looks around his home in the South African town of Kimberley and says, "Hello." Shortly after his accident, Johanna had turned down the option of letting him die.

    Three hundred miles away, Louis Viljoen, a young man who had once been cruelly described by a doctor as "a cabbage", greets me with a mischievous smile and a streetwise four-move handshake. Until he took the pill, he too was supposed to be in what doctors call a persistent vegetative state.

    Across the Atlantic in the United States, George Melendez, who is also brain-damaged, has lain twitching and moaning as if in agony for years, causing his parents unbearable grief. He, too, is given this little tablet and again, it's as if a light comes on. His father asks him if he is, indeed, in pain. "No," George smiles, and his family burst into tears.

    It all sounds miraculous, you might think. And in a way, it is. But this is not a miracle medication, the result of groundbreaking neurological research. Instead, these awakenings have come as the result of an accidental discovery by a dedicated - and bewildered - GP. They have all woken up, paradoxically, after being given a commonly used sleeping pill.

    Across three continents, brain-damaged patients are reporting remarkable improvements after taking a pill that should make them fall asleep but that, instead, appears to be waking up cells in their brains that were thought to have been dead. In the next two months, trials on patients are expected to begin in South Africa aimed at finding out exactly what is going on inside their heads. Because, at the moment, the results are baffling doctors.

    The remarkable story of this pill and its active ingredient, zolpidem, begins in 1994 when Louis Viljoen, a sporty 24-year-old switchboard operator, was hit by a truck while riding his bike in Springs, a small town 30 minutes' drive east of Johannesburg. He suffered severe brain injuries that left him in a deep coma. He was treated in various hospitals before being settled in the Ikaya Tinivorster rehabilitation centre nearby. Doctors expected him to die and told his mother, Sienie Engelbrecht, that he would never regain consciousness. "His eyes were open but there was nothing there," says Sienie, a sales rep. "I visited him every day for five years and we would speak to him but there was no recognition, no communication, nothing."

    The hospital ward sister, Lucy Hughes, was periodically concerned that involuntary spasms in Louis's left arm, that resulted in him tearing at his mattress, might be a sign that deep inside he might be uncomfortable. In 1999, five years after Louis's accident, she suggested to Sienie that the family's GP, Dr Wally Nel, be asked to prescribe a sedative. Nel prescribed Stilnox, the brand name in South Africa for zolpidem. "I crushed it up and gave it to him in a bottle with a soft drink," Sienie recalls. "He couldn't swallow properly then, but I helped him and sat at his bedside. After about 25 minutes, I heard him making a sound like 'mmm'. He hadn't made a sound for five years.

    "Then he turned his head in my direction. I said, 'Louis, can you hear me?' And he said, 'Yes.' I said, 'Say hello, Louis', and he said, 'Hello, mummy.' I couldn't believe it. I just cried and cried."

    Hughes was called over and other staff members gathered in disbelief. "Sienie told me he was talking and I said he couldn't be - it wasn't possible," she recalls. "Then I heard him. His mother was speechless and so were we. It was a very emotional moment."

    Louis has now been given Stilnox every day for seven years. Although the effects of the drug are supposed to wear off after about two and a quarter hours, and zolpidem's power as a sedative means it cannot simply be taken every time a patient slips out of consciousness, his improvement continues as if long-dormant pathways in his brain are coming back to life.

    I see Louis before his daily medication, yet he is conscious where once he would have been comatose. Almost blind because of a separate and deteriorating condition, there is a droop to one side of his mouth and brow because of brain damage. His right arm is twisted awkwardly into his side.

    Louis is given a pill, and I watch. It is 8.30am. After nine minutes the grey pallor disappears and his face flushes. He starts smiling and laughing. After 10 minutes he begins asking questions. His speech is impaired because of the brain damage and the need, several years ago, to remove all his teeth, but I can understand him. A couple of minutes later, his right arm becomes less contorted and the facial drooping lessens. After 15 minutes he reaches out to hug Sienie. He pulls off her wedding ring and asks what it is. "It's a suffer-ring," she jokes. And he says, "Well, if you're suffering, you should make a plan!" The banter continues and he remembers conversations from the previous day and adds to them.

    "Louis," I ask, "do you feel any change in awareness before and after the pill?" "No," he says. "None whatsoever." Whatever is happening, he feels the same. "How do you know this is your mother?" I ask, referring to Sienie. Remember, Louis cannot see. He says: "Because I recognise her voice and I know she loves me."

    Nel was as amazed at Louis' awakening as everyone else. A GP in Springs for 40 years, when he isn't seeing up to 100 patients a day, he spends his time restoring vintage cars. Married with three grown-up children, he has lived in the same house all his life.

    "Something strange and wonderful is happening here, and we have to get to the bottom of it," he says. "Since Louis, I have treated more than 150 brain-damaged patients with zolpidem and have seen improvements in about 60% of them. It's remarkable."

    After Louis' awakening was publicised in the South African media, Dr Ralf Clauss, a physician of nuclear medicine - the use of radioactive isotopes in diagnostic scans - at the Medical University of Southern Africa, contacted Nel to suggest carrying out a scan on Louis. "The results were so unbelievable that I got other colleagues to check my findings," says Clauss, who now works at the Royal Surrey County Hospital in Guildford. "We did scans before and after we gave Louis zolpidem. Areas that appeared black and dead beforehand began to light up with activity afterwards. I was dumbfounded - and I still am."

    Clauss says immediate improvements in the left parietal lobe and the left lentiform nucleus were visible. In lay terms, these are important for motor function, sight, speech and hearing.

    "I remember saying to Dr Nel that we were witnessing medical history," says Clauss.

    No one yet knows exactly how a sleeping pill could wake up the seemingly dead brain cells, but Nel and Clauss have a hypothesis. After the brain has suffered severe trauma, a chemical known as Gaba (gamma amino butyric acid) closes down brain functions in order to conserve energy and help cells survive. However, in such a long-term dormant state, the receptors in the brain cells that respond to Gaba become hypersensitive, and as Gaba is a depressant, it causes a persistent vegetative state.

    It is thought that during this process the receptors are in some way changed or deformed so that they respond to zolpidem differently from normal receptors, thus breaking the hold of Gaba. This could mean that instead of sending patients to sleep as usual, it makes dormant areas of the brain function again and some comatose patients wake up.

    In Kimberley, the once booming home of the De Beers diamond empire, Riaan Bolton's family heard of Nel's work after he and Clauss had papers published in the medical journal NeuroRehabilitation and the New England Journal of Medicine several months ago. Riaan suffered severe brain trauma when he was thrown from a car in a traffic accident in July 2003. A keen cricketer and rugby player, the 23-year-old was studying to become an industrial engineer but still found time to play guitar in a band.

    "One specialist said he had a 5% chance of recovering, another said he had no chance whatsoever of regaining consciousness," says his mother, Johanna. She and her husband, Tinus, spend about £1,000 a month on round-the-clock care for their son in a converted garage at their home, but until June they had seen no sign of awareness in him. Then they asked their doctor, Clive Holroyd, to contact Nel for advice.

    "There was no movement, no recognition, just nothing," says Tinus. "Then we gave him the pill and we noticed him moving the fingers in his left hand and touching them against each other. His eyes went big and he began looking from left to right.

    "The doctor started asking Riaan questions. He said, 'Look at me, Riaan' and Riaan looked straight at him and focused on his face. Then the doctor asked him to move his hand and he moved it. And then he lifted his head from the pillow and began looking around. I couldn't believe it."

    I watch as Riaan is given his medication. As with Louis, his face flushes and his eyes begin to sparkle and focus within minutes. Gone is the 1,000-yard stare. He hugs his mother and looks at her face, but even though I am amazed, the family reckon this isn't his best day so far. They show me a number of DVDs they shot in July. In them, Riaan responds to questioning, nods and shakes his head, drinks through a straw, often laughs and says, 'Hello.' He remains severely brain damaged, but there is clear evidence of understanding and communication.

    "It has given us hope," says Johanna. "To have communication with him again, to know he becomes aware of us and to tell him we love him - knowing he can hear us - is simply beyond belief. It has been a very moving experience."

    Holroyd remains perplexed. "There is a measurement of the depths of coma called the Glasgow scale, with three being the worst and 15 being normal," he says. "Riaan was six, but within 10 minutes of taking the pill he is up to nine. It's simply unbelievable. And the mind-boggling thing about this is that it's done with a sleeping pill.

    "Some time ago, Riaan had a cardiac arrest and it was a difficult call as to whether or not to resuscitate him. His mother insisted he should be, and look at him now. From now on, this will cause serious ethical issues over whether to let such coma victims die." Those issues became even more complicated last week, when a British woman believed to be in a persistent vegetative state astonished doctors by responding to their voices.

    Although these awakenings are the most dramatic aspect of the zolpidem phenomenon, Percy Lomax, the chief executive of ReGen Therapeutics, the British company funding the South African trials, believes Nel's work with less brain-damaged patients could be the most significant. Many stroke victims, patients with head injuries and those whose brains have been deprived of oxygen, such as near-drowning cases, have reported significant improvement in speech, motor functions and concentration after taking the drug.

    "The potential for this drug is enormous," says Lomax. "ReGen has applied for a patent to use the drug, now out of patent and generically available, for the treatment of secondary brain injury after brain trauma. The object of the clinical trial is to scientifically establish that the compound works in the way it has been shown to work in individual cases. It will be carried out on patients known to react well to zolpidem, and by lowering the dosage it is hoped that the sedative side-effects will be reduced but the brain stimulation will still continue.

    "It may be that further research will allow us to better understand the way the drug works and to develop a new generation of better-targeted pharmaceuticals." He says market research estimates the potential market for zolpidem in brain-damaged patents could top $4.3bn (£2.3bn).

    The company that first developed zolpidem, Sanofi-Aventis, was contacted by Nel and Clauss but appears to have chosen not to become involved in the trials or the use of the drug on brain-damaged patients. Instead, the brain scans on up to 30 patients will be carried out at the Pretoria Academic Hospital by Professor Mike Sathekge, head of nuclear medicine, and Professor Ben Meyer, one of South Africa's most renowned physicians.

    "The results so far could be potentially very important," says Meyer. "We have never before spoken of damaged cells in the brain going into hibernation - we have thought of them as necrotic, or dead, cells. But we know cells can go into hibernation in the heart and thyroid, so why not the brain? If there are hibernating cells in damaged brains, it may be that this drug helps to wake them in some people."

    In South Africa, I meet a procession of brain-damaged patients who feel the drug has changed their lives for the better. There is 32-year-old Miss X, who can't be named for legal reasons. She suffered four cardiac arrests and hypoxia, a lack of oxygen to the brain, when a hospital's apparent failure to diagnose a gall bladder problem resulted in her contracting septicaemia four years ago. She can barely stand, her arms are in spasm, she cannot speak - although her intelligence has not been affected - and the left side of her face droops. She was given zolpidem for the first time just a week before I see her and her parents say the improvement was such that she has come back for more.

    Miss X is given a pill by Nel at 4.37pm. By 4.50 the left side of her face is no longer drooping, her eyes sparkle and she smiles broadly. At 5.02, her arms have relaxed enough for her to fold them and she is laughing with her parents. Ten minutes later, she stands up, stretches to her full height and claps her hands.

    Using a card keyboard, she spells out answers to questions I have for her. "Can you use the keyboard more quickly with the medication?" She answers: "Yes." Does she feel an improvement? "Yes, I am not falling over. I am not coughing so much. I can swallow easier. I feel my limbs are much more relaxed." But does she feel more tired? "No". What is she hoping for? "To talk again. I'd love to be able to call my cats to come to me."

    At 5.22pm, Miss X issues a long, drawn-out "Wall-eeee!" and hugs Nel.

    Then there is Wynand Claasens, 22, who suffered severe brain damage five years ago when he was assaulted outside his school. A series of subsequent strokes left him wheelchair-bound, depressed and aggressive. He used to be a long-distance runner. Nel gave him Stilnox for the first time in early July this year. "I was struggling to walk, my left eye was hanging lower and was smaller than my right eye, I was feeling very angry, I had pains in my knees and I was having trouble going to the toilet," Wynand says. "Now I'm walking with one stick, my face has evened up, I can go to the toilet when I'm ready and the pain in my knees has gone. I take one 10mg tablet each night and I feel about 60% better."

    The list goes on. Heidi Greven, who is now 21, was starved of oxygen to her brain at birth. Her mother, Babs, says she used to sit in silence, locked inside her own head, never communicating and looking terribly unhappy. When I meet Heidi, she is walking around, curious about everything. She examines the shorthand in my notebook. Although too shy to speak (she will always be brain damaged), she jokes with Nel. At home, she now chats with her parents.

    "I'll never forget the first time she was given the medication," says Babs. "It was in July 2002. After 10 to 15 minutes it was like a curtain being lifted from her eyes. I couldn't believe it. She suddenly started looking around and fiddling with magazines. Then she went outside the door and looked into the other rooms in the surgery. She found a portable radio and put it up to her shoulder and began listening to it. Beforehand, she would just sit there doing nothing.

    "That was a Saturday. When she went to [a special] school on the Monday, her teacher sent a note home asking what we had done to make Heidi come alive."

    There are others, too: Paul Ras, a 69-year-old runner who suffered brain damage after a traffic accident. Now he is convinced zolpidem is responsible for a recovery that allows him to run races up to 50km - with only one hip.

    And Theo van Rensburg, a 43-year-old lawyer who suffered severe brain injuries in a car crash in 1991. He also suffered a stroke while in a coma for three months. He took Stilnox in 1999 and reported an improvement in balance, co-ordination, speech and hearing.

    "I go horse-riding now," he says. He still has difficulty speaking, but I can understand him. "It's really good for my balance."

    Finally, I meet 22-year-old Janli de Koch, whose eyesight was damaged in a car accident in Switzerland in December 2004. The injury resulted in a restriction of her visual field to two corners of her eyes; she cannot see below a certain point, so that she bumps into things and falls over. Last month, she was prescribed zolpidem and now says she can already see more than she used to. She hopes the improvements will continue.

    In 1969 the neurologist Dr Oliver Sacks used the then new drug L-Dopa to awaken a group of catatonic patients who had survived the 1917-1928 epidemic of the mysterious "sleeping disease", known as encephalitis lethargica. The 1990 film Awakenings chronicles Sacks' delight at his patients' progress and his despair when the medication stops working and they slip back into a catatonic state. The hope with zolpidem is that the improvements will continue and there will be no regression. In the patients who have used the medication longest - such as Louis Viljoen and Theo van Rensburg - the signs are that progress continues. But time will tell.

    Perhaps the last word should go to Pat Flores, the mother of George Melendez, the 31-year-old coma patient who reassured his parents that he wasn't in pain after taking Ambien, as zolpidem is known in the US. He was starved of oxygen when his car overturned and he landed face down in a garden pond near his home in Houston, Texas, in 1998. "The doctors said he was clinically dead - one said he was a vegetable," says Pat. "After three weeks he suffered multi-organ failure and they said his body would ultimately succumb. They said he would never regain consciousness."

    He survived and four years later, while visiting a clinic, Pat gave him a sleeping pill because his constant moaning was keeping her and her husband, Del, awake in their shared hotel room. "After 10 to 15 minutes I noticed there was no sound and I looked over," she recalls. "Instead of finding him asleep, there he was, wide awake, looking at his surroundings. I said, 'George', and he said, 'What?' We sat up for two hours asking him questions and he answered all of them. His improvements have continued and we talk every day. He has a terrific sense of humour and he carries on running jokes from the day before.

    "It is difficult to describe how it feels to get someone back who you were told you had lost for ever. There is a bond that has been restored and it validates our absolute belief that all along George was locked inside there somewhere. It tells us that we were right and the doctors were wrong. George, and his personality, were in there the whole time".

    What is persistent vegetative state?

    Though it sounds unkind to refer to a human in such terms, even medical dictionaries define persistent vegetative state (PVS) as the condition of living like a vegetable: in other words, existing without consciousness or the ability to initiate voluntary action. Though people in this state may occasionally give the impression of being awake and sentient, making random movements and opening their eyes and even appearing to smile or cry, they are unable to respond to communication or demonstrate awareness of their environment. This is different from an ordinary coma, in which the patient's eyes are closed, and which rarely last more than four weeks. The other key difference is that a person in a coma hasn't necessarily lost all cognitive function (ie, brain power); they are just temporarily unable to access it. If they recover - and many do - they may have cognition afterwards.

    PVS is the result of irreparable damage to the cerebral cortex - the "thinking, feeling" part of the brain - but it is not to be confused with brain death. And while the "persistent" bit in the title indicates that the condition, unlike coma, is generally deemed permanent, there are intermittent reports of "recoveries". Last week, it was reported that a 23-year-old woman who has been in a vegetative state since suffering devastating brain damage in a traffic accident was suddenly able to understand speech. And in 2003 an Arkansas man, Terry Wallis, returned to consciousness 19 years after he was injured in a car accident, stunning his mother by saying "Mom" and then asking for a drink of fizzy pop. Such breakthroughs are controversial, in both medical and legal circles. The British Medical Association, for example, currently deems such miraculous events not as recoveries from PVS, but as an indicator of an earlier misdiagnosis.

    Because legal systems do not generally equate PVS with death, and diagnosis is difficult, there have been several famous court cases involving people in this condition. The most high-profile centred on Terri Schiavo, a 26-year-old Florida woman who went into a PVS after collapsing and suffering a heart attack in 1990. In 1998 her husband, Michael Schiavo, petitioned for her gastric feeding tube to be removed; her parents did not believe the diagnosis and took the case to court to prevent medical care being withdrawn. Ultimately, the court challenges were unsuccessful and in 2005 Schiavo's feeding tube was removed, leading to her death.

    There is no treatment for PVS. Instead, the medical team concentrate on preventing infections and maintaining the patient's physical state as much as possible. The most common cause of death for a person in a vegetative state is infection such as pneumonia. For most such patients, life expectancy ranges from two to five years; survival beyond 10 years is unusual.


    by Steve Boggan
    The Guardian, Tuesday 12 September 2006

    Hello everyone.

    My father fell into a coma after a brain hemmorage and did not recover. Thankfully there is research being done on this subjuct, ie using Zolpidem or Stilnox/Ambien to wake people up.

    The below helps give a backround to what is currfently being researched.

    The sedative zolpidem (marketed by Sanofi-Aventis under the trade names Stilnox™ and Ambien™) has been used for the last twenty years as a hypnotic/sedative by millions of people.
    Several years ago Dr Wally Nel, a General Practitioner in South Africa, discovered that zolpidem promoted remarkable recoveries in some patients who were treated with it for insomnia, following traumatic brain injury and stroke. In a case report published in a South African medical journal in 2000, Dr Nel and his co-worker Dr Ralf Clauss described how approximately fifteen minutes after an oral dose of zolpidem was administered to a patient who had suffered a road traffic accident three years previously, he awoke from his semi-comatose condition and remained awake for the next 3-4 hours and when drug action subsided he returned to his previous state. That same patient is now awake for up to 10 hours a day after eight years of daily treatment with zolpidem. Further studies in Dr Nel’s clinic have now shown that many subjects with brain-injury caused in various ways and with various degrees of severity have consistent and reproducible improvement in their clinical features when given zolpidem.
    While Dr Nel continued his work in South Africa, Dr Clauss moved to the UK, where he teamed up with Dr Andrew Sutton (medical consultant to ReGen). Together with Dr Nel, they formed Sciencom Ltd and filed an international patent application covering this new use for zolpidem. This patent has since been approved in South Africa and is still pending in other countries.
    In February 2006, ReGen Therapeutics Plc acquired the entire share capital of Sciencom and with it the rights to the company’s patent application and the rights to continue to develop its zolpidem project.
    ReGen believes that both a clear “therapeutic need” and a significant commercial opportunity exist for new, low-dose, non-sedating formulations of zolpidem, to enable this important clinical benefit to be optimally delivered to a diverse range of patients.
    In August 2007, ReGen reported on a Clinical Study, which confirmed that a 2.5mg novel formulation of zolpidem is non-sedating when used on conscious, fully perceptive, ambulant patients having various debilities as a consequence of brain damage. It was performed in collaboration with the Company’s subsidiary, Guildford Clinical Pharmacology Unit Limited and investigators at the Walko Medical Centre in Springs, South Africa where the 'antidormancy' effect of zolpidem was first discovered.
    The study compared various single doses of a novel sublingual spray formulation (placebo, 2.5mg, 5mg, 10mg) with an existing tablet formulation (placebo, 10mg) in terms of the onset and degree of sedation. It also looked for preliminary signs of efficacy.

    The results showed that a 2.5mg spray was no more sedating than a placebo. The 10mg and 5mg sprays induced sedation in a dose responsive manner and the spray showed faster onset of action (sedative effect) than the tablet. The 5mg spray induced the same peak level of sedation as the 10mg tablet - 15 minutes compared with 90 minutes respectively.

    ReGen is planning a further trial, which is scheduled to start in 2008 and will involve a significant number of outside experts in the field, to establish the efficacy of zolpidem in reversing brain dormancy. Scientific investigations into the way zolpidem works in this situation are also continuing.
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