Health & Medical M&G's Science Voices

SCIENCE VOICES: The sleeping pill that wakes up damaged brains

Top-down molecular model of the cellular receptor (GABA) to which Zolpidem binds. (Illustration: Dr Andre Stander)
Top-down molecular model of the cellular receptor (GABA) to which Zolpidem binds. (Illustration: Dr Andre Stander)

Between our love for contact sports and our shocking road traffic injury figures, South Africans are at the troubling end of head trauma statistics, writes Petrie Jansen van Vuuren, a MSc candidate at the University of Pretoria.

A conservative estimate, based on hospital records from the 1990s, estimates that 170 000 people sustain brain damage every year. Sadly there is little than can be done to treat an injured brain, with the majority of post-accident interventions focussing on preventing further damage. Many of these patients end up in rehabilitative or palliative care for the rest of their lives. This is where our research on Zolpidem comes in.

As a researcher, I remember the first time that I was introduced to a group of Zolpidem responder patients. It’s not quite the elegant tale of the confident young neuroscientist swooping in with a charming smile and excellent bedside manner to have rousing conversations with enthusiastic patients who had been completely restored by a wonder drug.

Instead, I stood frozen in the doorway of a small preparation ward, caught completely off guard by the three families in front of me as a nurse armed with syringes encased in lead shields moved between vulnerable patients with militant precision. She was administering a radioactive tracer in preparation for a SPECT scan, a unique way of imaging brain function by measuring blood flow.

The three patients, each with varying forms of brain damage, were lying on hospital beds. One was asleep. The other two were suffering incapacitating muscle spasms as their significant others sat next to their beds gingerly trying to do whatever they could to comfort their loved ones.

I was acutely aware of the immense importance of this research and any associated discoveries, as even the smallest improvements can have a large impact on these bed-ridden patients’ quality of life.

Selling at just over R7 per 10mg tablet, Zolpidem, originally marketed as Stilnox in South Africa, was developed by the French pharmaceutical corporation Sanofi-Aventis as a sleeping pill. In healthy individuals, it decreases the amount of time required to fall asleep (known as sleep latency). But if you give this pill to someone with brain damage, in 5% to 6% of cases something miraculous happens. Often it’s a small change, an improvement in speech, reduced muscle spasms, improved gait. In drastic cases, patients are roused from vegetative states, returning to consciousness after many months, even years, of being completely unresponsive. It is these unbelievable events that have led to Zolpidem being dubbed by some as a “Lazarus Drug”.

The problem is, no one knows exactly how it is able to restore function to damaged brains. Bizarrely, once the drug wears off, so do the beneficial effects and vegetative patients are once again subconscious. If the dose is too high, the beneficial effects give way to the drug’s action as a sleeping pill.

So far researchers have been unable to pinpoint which patients will respond positively to the drug. There does not seem to be a particular type of brain damage or damage to a particular region of the brain that dictates, with certainty, whether there will be a rehabilitative response to Zolpidem. But that has not stopped researchers from hypothesising.

Sadly neither of these hypotheses is perfect, or able to explain the complex spectrum of Zolpidem-related phenomena. However, researchers are still trying to take full advantage of Zolpidem’s unique action as well as developing new drugs which work in a similar manner. Despite the theoretical uncertainties, Zolpidem offers a glimmer of hope for many families coping with the aftermath of a loved one’s brain injury.

To read Petrie Jansen van Vuuren’s full story, please visit the Mail & Guardian website.

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