Med thumb raised awareness

As sleep aids go, Ambien does a bang-up job. Pop a pill and 30 minutes later, you’re passed out, drooling with aplomb. But, researchers have discovered uses for the popular sedative beyond conquering insomnia (and Ambi-tripping). According to one recent study, for example, Ambien may be the first and only drug capable of expediting stroke recovery. Its role in restoring brain function, however, isn’t limited to strokes. For brain injury patients with “Disorders of Consciousness,” Ambien may be the key to waking up.

Evidence of this paradox — a sleeping pill for arousal and alertness — comes from a handful of medical case studies and speck-sized clinical trials, as explained in a new review paper, published in the journal Neurocritical Care. In other words, using Ambien to rescue people from various states of mental inertia is far from the norm. For now.  

Disorders of Consciousness, the hypothesis goes, are caused by the depletion of oxygen-dependent neurotransmitters following a brain injury. Brain injuries come in two varieties: traumatic (think: football concussions) and non-traumatic (think: strokes, neurodegenerative disease). Brain injuries may be ischemic in nature, meaning that oxygen deprivation is caused by disrupted blood flow. Or, they can be hypoxic, meaning the culprit is reduced oxygen availability. Non-traumatic injuries marked by total (rather than partial) oxygen deprivation are called “anoxic.”

But, let’s put the classifications aside and go the simple route: Brains need oxygen. Every minute, the three-pound organ uses about 3.3 ml of oxygenated blood per 100 grams of brain tissue. And, deprived of the life-sustaining gas, people can fall into the prolonged state of unconsciousness known as coma. After the initial coma subsides, patients may regain just enough brain function to hover above the flat line and receive a new diagnosis: Disorder of Consciousness (DOC). Those left in a vegetative state (VS) are awake but unconscious, whereas DOC patients in a minimally conscious state (MCS) exhibit “inconsistent but reproducible evidence of environmental awareness,” such as blinking.

For brain injury patients with “Disorders of Consciousness,” Ambien may be the key to waking up.

Some comas are like diamonds (forever), but other DOC patients regain at least partial brain function. Still, per the study, there are no treatments shown to enhance consciousness recovery on a consistent, reliable basis. In a few cases, doctors have seen sporadic recovery after administering stimulants. Presumably, stimulating a barely conscious brain makes logical sense. But it also may not be the most effective method of trouncing a vegetative state. Ambien, on the other hand, has a decent track record.

Study authors Calvin Tucker and Kirsten Sandhu, both pharmacology researchers, reviewed medical literature from 1960 to 2014, and found seven case reports and seven clinical studies concerning Ambien as treatment for DOC. In 10 of the 14 articles, patients showed improved neurological function.

Patients who did respond to Ambien showed increased blood flow (indicative of arousal) in several regions of the brain within an hour of administration. Arousal typically lasted between three and four hours. Basically, the drug reliably kicked in quickly for coma patients, just as it does for insomniacs. This suggested to study authors that Ambien woke up the brain through “acute changes in neurotransmitter discharge rather than long-term changes in neuronal plasticity.” In other words, Ambien fires up neurons like a Hibachi chef scorching shrimp, rather than through enabling the longer-term growth or repair of neural connections.

Ambien fires up neurons like a Hibachi chef scorching shrimp, rather than through enabling the longer-term growth or repair of neural connections.

Patients with non-traumatic injuries exhibited stronger responses than those who suffered trauma. Anoxic patients — again, who endured total oxygen deprivation — exhibited arousal from Ambien as early as one month, and as late as five years, after their injuries. But, in these cases, study authors noted the difficulty of classifying drug-induced brain arousal as a “successful” treatment experience. We don’t yet know enough about the relationship between observed brain activity (via imaging) and mental function in such highly damaged brains.

Not all patients, however, got the Ambien brain boost. Those who exhibited no subsequent change in neurological function, researchers wrote, may be related to a few factors, including the nature and extent of brain damage, duration of initial oxygen deprivation and location of brain injury.

Overall, study authors found convincing evidence to “suggest a relationship between the administration of Zolpidem and improved neurologic function in some patients.”

But they don’t know why. They do know, or at least believe, that the brain arousal appears to be Ambien-specific. Benzodiazepines (e.g., xanax) haven’t had the same impact. Why? Well, as a refresher: Both Ambien and Benzos both work by acting on GABA, a mood-mellowing neurotransmitter, but Ambien targets GABA receptors more narrowly. So, Xanax has broader effects, doubling as a drug for anxiety and sleep, whereas Ambien is just a very powerful sedative. A powerful sedative that could awaken those caught in conscious limbo.