To evaluate whether zolpidem improves arousal and progress towards a fully conscious state in patients with prolonged disorders of consciousness (PDOC) due to acquired brain injury.

Studies that have analyzed the usage of zolpidem for treating PDOC have shown conflicting results. In this study, we evaluated whether our zolpidem regimen promotes a progression towards a fully conscious state, and whether there are differences in response with respect to age, sex, etiology, and discharge destinations.

We identified patients who presented to the post-acute specialty neuroscience program at Nexus Health Systems between 01 October 2018 and 31 January 2021 with a confirmed diagnosis of PDOC, using retrospective review. Patients were treated with 30 mg/day in divided doses of zolpidem.

Coma Recovery Scale-Revised (CRS-R) scores were used to categorically assess changes in the level of consciousness in response to treatment. Patients who transitioned from the unresponsive wakefulness syndrome or minimally conscious state minus (MCS-) to MCS+ or emergence from MCS (eMCS), were considered as responders.

Of the 75 patients, 29(39%) transitioned to MCS+ and 21(28%) transitioned to eMCS. 17 responders (23%) reached and sustained a maximum CRS-R score of 23 and were discharged to lower level of care for further recovery.  Non-responders had a significantly lower pre-treatment mean CRS-R score than responders (3 vs 6, p < 0.001). The median duration of treatment was similar in both responders and non-responders (8.3 vs 8 weeks, p =0.86). No significant differences were observed according to sex, age, or etiology, between the response groups.

This study is a preliminary indicator that the use of 30 mg/day of zolpidem may lead to significant improvements in quality of life in a subset of patients with PDOC. Pre-treatment CRS-R scores may be a potential predictor of response. Further large-scale controlled investigation is needed to confirm causality and efficacy.