Zolpidem for Recovery of Consciousness: Does It Work?

Joanna M. Pangilinan, PharmD

Disclosures

October 01, 2014

Question

Is zolpidem use associated with recovery of consciousness in comatose, vegetative, and minimally conscious patients?

Response from Joanna M. Pangilinan, PharmD
Pharmacist, Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, Michigan

Traumatic, ischemic, or anoxic brain injuries may cause disorders of consciousness (DOC) that include coma, vegetative state, and the minimally conscious state. Some survivors of brain injury have prolonged periods of depressed consciousness.[1]

Some case reports in patients with DOC describe a transient improvement in consciousness associated with the hypnotic zolpidem—a seemingly counterintuitive effect. Zolpidem is a nonbenzodiazepine gamma-aminobutyric acid (GABA) agonist. GABAergic terminals and interneurons are found in most brain areas and release of GABA facilitates transition to sleep. Drugs like zolpidem promote sleep by enhancing GABAergic transmission.[2] Zolpidem binds selectively to the GABA omega-1 receptor subtype resulting in strong hypnotic effects and weak anxiolytic, anticonvulsant, and myorelaxant properties.[3] The mechanism by which zolpidem may improve consciousness is unknown.[1,3] Some researchers theorize that it may promote reactivation of neural networks that are "dormant."[3]

Studies have been performed to evaluate the use of zolpidem in patients with DOC. A placebo-controlled, double-blind, single-dose, crossover study evaluated the effect of zolpidem in 84 patients who had DOC for at least 4 months. The level of consciousness was quantified using the Coma Recovery Scale-Revised. Researchers identified four "definite responders" (4.8%) by professional assessment. Increased movement, social interaction, following of commands, communication attempts, and functional object use were indicators of zolpidem response. However, drug response usually lasted 1-2 hours, and some patients had resulting somnolence. No predictive demographic or clinical features were identified.[1]

One study used a digital cerebral state monitor and single-photon emission CT (SPECT) to evaluate the efficacy of zolpidem in patients in a persistent vegetative state after brain injury. One hour after receiving 10 mg, researchers found that cerebral state index was increased and burst suppression reduced in space-occupying brain compression and brain contrecoup contusion groups. In addition, SPECT showed that cerebral perfusion was improved in both of these groups. Noted improvement of brain function was found to be sudden and not gradual. The authors concluded that zolpidem was effective especially for patients whose injuries were mainly in nonbrainstem regions.[4]

Most patients with DOC do not benefit from zolpidem. Some cases and studies have reported minimal or no benefit for restoring consciousness.[1,2,5,6] Response rates appear to be very low.

Although zolpidem has shown some encouraging results in a small number of patients with DOC, the benefits seem limited and transient. Hence, zolpidem is not considered a part of routine care, and experts recommend caution to "avoid hasty conclusions based on sporadic case reports."[2] Currently, its use in this complex population should be considered on a case-by-case basis. More research is needed to elucidate the mechanism of zolpidem and its potential role in patients with DOC.

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