Abstract
OBJECTIVE:

The aim of this study was to determine if zolpidem is associated with improved responsiveness or regional cerebral perfusion in patients with persistent vegetative states.
METHODS:

Following ethics approval, children with persistent vegetative state were enrolled in a prospective, double-blind, placebo-controlled randomised trial. Patients underwent 2 treatments of 4 days, separated by 10 days. Each child received either a daily dose of zolpidem or placebo with a dosage of 0.14-0.2 mg/kg. Responsiveness and regional cerebral perfusion were the outcomes of interest. These were assessed using the Rancho levels of cognitive functioning scale, the coma/near-coma scale and F (1-FDG positron emission tomography. These were conducted at baseline and after completion of the treatments.
RESULTS:

3 children were enrolled. The Rancho assessment scales showed no change with treatment. The coma/near-coma scale showed a tendency to increase with zolpidem, suggesting reduced responsiveness - when compared to baseline or placebo. The positron emission tomography scans showed no significant changes between treatments.
CONCLUSION:

Zolpidem was associated with a tendency towards reduced responsiveness in patients with persistent vegetative states. There were no objective changes on positron emission tomography suggestive of an associated increase in cerebral blood flow with zolpidem. It would appear that zolpidem does not offer a beneficial effect in this setting.

Abstract
OBJECTIVES:

The common hypnotic, zolpidem, has been reported to temporarily restore consciousness to individuals in the chronic vegetative state. In drug responders, repeated dosing appears to maintain consciousness. The frequency of such responses, however, is unknown and is important both to guide clinical use and to plan further research on the mechanisms underlying drug response. The objectives of this study were to obtain an estimate of the frequency of clinically significant responses among individuals with disorders of consciousness, to determine whether less obvious drug responses are present among "nonresponders," and to identify clinical features characteristic of zolpidem responders.
DESIGN:

Participants were individuals in the vegetative or minimally conscious state at least 1 month after brain injury. Each participant was studied individually in a double-blind, placebo-controlled, crossover design, once on zolpidem (10 mg per feeding tube) and once on placebo. Each assessment involved baseline administration of the Coma Recovery Scale-Revised, followed immediately by administration of the study drug, followed by 5 hourly readministrations of the Coma Recovery Scale-Revised. A replication pair of assessments was available for drug responders.
RESULTS:

: One of 15 participants (6.7%) demonstrated a clinically significant response, which altered his assessment from the vegetative state to the minimally conscious state, and this result was repeated in the replication assessment. The remaining 14 participants showed no evidence of a subclinical response to the drug.
CONCLUSION:

These results confirm that clinically significant responses to zolpidem among individuals with disorders of consciousness do occur in a minority of patients and can be replicated. Failure to find a trend toward improved performance on zolpidem among nonresponders suggests a bimodal rather than a graded response to the drug. The fact that only one drug responder was identified in this small study prevents assessment of features characteristic of drug responders.