A girl who has spent six years in a coma is showing signs of life after taking a sleeping pill.
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Amy Pickard before she fell unconscious in 2001 and with her mother Thelma while in hospital
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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.
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Amy as she is now, fighting her way to recovery
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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.
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."
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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. 