by Alicia M Prater PhD

Created on: December 25, 2011   Last Updated: April 27, 2012

Roughly a decade ago doctors stumbled on something unbelievable – patients in comas were stimulated to waken by drugs usually given as sleeping aids. It was not until recently that this potential was actually seeing use in clinical settings, though studies have been showing that the paradox was not a fluke. The drug of interest is zolpidem, which is sold under the brand name Ambien and is one of the world’s most popular sleeping pills.

What is zolpidem?

Zolpidem belongs to a class called sedative-hypnotics and is prescribed as a short-term treatment for insomnia. The drug acts on the brain, causing its activity to slow down. It acts very quickly, inducing and maintaining sleepiness for 7 to 8 hours. However, a recent phenomenon has become associated with such pills – that of sleep activity. People drive their cars and don’t remember, eat and don’t remember, have accidents and don’t remember – so what the drug actually does to the brain is somewhat shrouded in mystery.

The beginning of a paradox

As reported in the New York Times magazine in December 2011, the first patient to experience the waking coma paradox was being treated in South Africa in 1999. After being hit by a truck in 1994, Louis Viljoen suffered brain damage and lay in a deep coma. Doctor Wally Nel thought that his bed clawing reflexes could be calmed with sedation, so according to The Guardian he prescribed Stilnox (South African brand name for Ambien). Instead, it woke him up. Within 30 minutes of his mother giving him the medication, he began to hum. Then he began to talk. As of 2006 he was still taking daily pills, allowing a few hours of lucidness a day – with his state continuing to improve with treatment.

By 2006 doctors on three different continents reported coma patients regaining brain functions when given some version of zolpidem. In 2007, French researchers inadvertently found that, in brain damaged patients, the drug did in fact increase alertness and improve language and motor skills. A woman with a rare condition in which she was conscious but unable to communicate was given zolpidem for her insomnia. She began having breaks in her condition. At the time, such treatment for persistent vegetative state was considered a long-shot, but showing potential with a number of individuals who were otherwise written off.

Waking coma patients with sleeping pills?

The doctors who have worked with the South African clinic where the paradox began think the power of the sleeping pill lies in its effects on GABA. When the brain suffers damage, this neurochemical shuts down the neurons to preserve them. In coma patients the chemical simply does its job too well. Perhaps zolpidem reshapes the GABA receptors, allowing them to take a break from keeping the brain cells shut off.

The treatment unfortunately does not work with every patient. A number have been found to be unresponsive, and for those who do react to it, they get an hour or two of function a day. Even this, though, is limited by the damage they sustained, with some only being awake. However, this paradox has opened doors for some patients and their families, and is part of the road of discovery underlying new advances in stimulating the brains of coma patients by other means.

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