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Am J Phys Med Rehabil. 2014 Feb;93(2):101-13. doi: 10.1097/PHM.0000000000000069.

Zolpidem and restoration of consciousness.

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From the Moss Rehabilitation Research Institute, Elkins Park, Pennsylvania (JW, RR); Park Terrace Care Center, Rego Park Queens, New York (AR); Department of Neurology, Boston University School of Medicine, Massachusetts (DK); Brain Injury Program, Braintree Rehabilitation Hospital, Massachusetts (DK); JFK Johnson Rehabilitation Institute Center for Head Injuries, Edison, New Jersey (KK); Crawford Research Institute and Brain Injury Program, Shepherd Center, Atlanta, Georgia (RS); Department of Rehabilitation Medicine, Icahn School of Medicine at Mt. Sinai, New York, New York (BG); Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (RZ); On With Life, Ankeny, Iowa (DD); Department of Physical Medicine and Rehabilitation, University of Alabama at Birmingham (RB); and Division of Physical Medicine and Rehabilitation, University of Louisville, Kentucky (DK).



Zolpidem has been reported to cause temporary recovery of consciousness in vegetative and minimally conscious patients, but how often and why this occurs are unknown. The authors aimed to determine the frequency of this phenomenon and whether it can be predicted from demographic and clinical variables.


This is a placebo-controlled, double-blind, single-dose, crossover study performed by caregivers and replicated by trained professionals, for naive participants. Four previously identified responders were also studied to further characterize the clinical drug response.


Eighty-four participants with traumatic and nontraumatic disorders of consciousness of at least 4 mos' duration were studied. Four "definite responders" were identified, but no demographic or clinical features were predictive of the response. Indicators of a drug response included increased movement, social interaction, command following, attempts at communication, and functional object use; typically lasted 1-2 hrs; and sometimes ended with increased somnolence. Adverse events were more common on zolpidem than placebo, but most were rated as mild.


Approximately 5% (4.8%) of the participants responded to zolpidem, but the responders could not be distinguished in advance from the nonresponders. Future research is needed to understand the mechanism of zolpidem in enhancing consciousness and its potential role in treatment and research.

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