Could a Sleeping Pill 'Wake Up' Coma Patients?


March 13, 2007 — -- 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.

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."

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.

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."