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Zolpidem (Stilnox) and Acquired Brain Injuries

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Zolpidem (Stilnox) and Acquired Brain Injuries

Zolpidem (marketed as Stilnox in Australia and Ambien in the USA) is a prescription drug mainly used to treat sleeping difficulties. Zolpidem has recently come to light in the media as a 'miracle cure' for patients (such as Sam Goddard) with neurocognitive disorders like a brain injury. Information on the drug is still emerging so it is important to approach claims of a possible cure with caution.


The positive evidence being presented currently for Zolpidem is that some patients with neurocognitive disorders resulting in minimally conscious states (MCS) or persistent vegetative states (PVS) have regained levels of consciousness and cognitive capacities following administration of Zolpidem.(1,2,3,8)


The alternative use of this drug was discovered in South Africa when a doctor prescribed Zolpidem to his patient with a neurocognitive disorder to assist with sleeping difficulties.(2) Thirty minutes following administration of this drug, the patient miraculously 'regained consciousness.(2,5) This enhanced consciousness is only evident for the two to four hours that Zolpidem is in the patient's system, and as the drug wares off so too does the effect. (2,5,8) This enhancement of the patient's level of consciousness has led many people to believe Zolpidem is the answer to "getting their loved one back" after a brain injury.


Why, then, is Zolpidem not being handed out, over the counter, to patients in need? Foremost, according to the Australian Therapeutic Goods Administration (ATGA), Zolpidem is recommended only for initiating and maintaining sleep for those who have sleeping difficulties. The practising physician would place at risk their professional medical indemnity if they were to prescribe the drug for something other than the purpose prescribed by the ATGA. The physician could be summoned at a later date to explain what evidence they had to substantiate prescribing Zolpidem, and if the evidence is lacking could incur great penalties including the loss of licence to practise. (9)


The AGTA is tasked with the role of determining safe and effective practices with regards to medication use. (9) As they are yet to state that Zolpidem is safe and effective for use in patients with a brain injury, one must begin to wonder why. (9) It could be assumed that this is due to the lack of evidence supporting the use of Zolpidem in people with neurocognitive disorders like a brain injury. Zolpidem has only been shown to reduce cognitive difficulties for around seven to ten percent of adults with neurocognitive disorders, with children yet to show any response. (5,8,12)


This group of patients reacts consistently to the drug, indicating that Zolpidem is the cause of the altered consciousness; however the other majority of patients have no positive cognitive reaction to Zolpidem. (6,8)

Zolpidem has also been known to have many negative effects during its use as a sleeping tablet (which is approved by the AGTA). Many patients reported committing a wide variety of activities (many hazardous) whilst sleeping, and not having any recollection of them (e.g. driving a car, sexual relations, and jumping off a balcony have been reported). This lead the ATGA to put a black box warning on the medication. Aside from sideeffects, Zolpidem has a similar withdrawal mechanism to benzodiazepines such as Valium. (10)


Withdrawal results in severe symptoms if the dosage is reduced dramatically in a short period of time. Similar to benzodiazepines is a propensity for tolerance build-up. It was noted that over time patients needed more Zolpidem to elicit sleep that came easily initially. (10)

Lastly, Zolpidem can have negative effects on both the central nervous system and the brain with long-term use.11 Memory loss and reduction in neuroplasticity in the brain have both been reported. (7,11) This is especially important in neurocognitive disorders as memory is often affected already. Neuroplasticity is what we rely on following a brain injury to rebuild connections, so even if Zolpidem resulted in temporary improvement, there are potentially serious long-term problems to consider.


As many people will argue, many of these side-effects only occur in a small amount of the population who take Zolpidem as a sleeping tablet; however it is important to view both sides objectively. The point of this article is not to decide for you what you should do. Synapse understands that many families are looking for anything that may assist their loved ones, and we eagerly look forward to the development of new approaches in treatment. What we have attempted to do here, however, is support you in making an informed choice based on sound evidence of both sides of the argument. Ultimately, it will be up to you and your GP to decide the best course of action. If your GP is uncomfortable with prescribing this drug, then this is his or her decision to make, as you are now aware of the risks you are asking them to take.

References and further information

  1. Castellanos, N. P., Bajo, R., Cuesta, P., Villacorta-Atienza, J.A., Paúl, N., Garcia-Prieto, J., del-Pozo, F. & Maestú, F. (2011). Alteration and Reorganization of Functional Networks: A New Perspective in Brain Injury Study. Frontiers inHuman Neuroscience, 5, 90. 14
  2. Chew, E. & Zafonte, R. D. (2009). Pharmacological management of neurobehavioral disorders following traumatic brain injury-A state-of-the-art review.Journal of Rehabilitation Research & Development, 46, 851-878. 1
  3. Clauss, R. P., Guldenpfenning, W. M., Nel, H. W., Sathekge, M. M. & Venkannagari, R. R. (2000).South African Medical Journal, 90, 68-72. 2
  4. Clauss et al 2010 3
  5. Hall, S., Yamawaki, N., Fisher, A. E., Clauss, R. P., Woodhall, G. L. & Stanford I. M. (2010). GABA(A) alpha-1 subunit mediated desynchronization of elevated low frequency oscillations alleviates specific dysfunction in stroke--a case report.Clinical Neurophysiology, 121, 549-550. 4
  6. Larson, E. B. & Zollman, F. S. (2010) The Effect of Sleep Medications on Cognitive Recovery From Traumatic Brain Injury.Head Trauma Rehabilitation, 25, 61-67. 11
  7. Nyakale, N. E., Clauss, R. P., Nel, W. & Sathekge, M. (2010)Clinical and brain SPECT scan response to zolpidem in patients after brain damage. Arzneimittelforschung, 60, 177-181. 5
  8. Sharan, P., Bharadwaj, R., Grover, S., Padhy, S. K., Kumar, V. & Singh, J. (2007). Dependence syndrome and intoxication delirium associated with zolpidem.The National Medical Journal of India.20, 180-181. 10
  9. Singh, R., McDonald, C., Dawson, K., Lewis, S., Pringle, A., Smith, S. & Pentland, B. (2008) Zolpidem in a minimally conscious state.Brain Injury, 22, 103-106. 6
  10. Snyman, N., Egan, J. R., London, K., Howman-Giles, R., Gill, D., Gillis, J. & Scheinberg, A. (2010). Zolpidem for Persistent Vegetative State - A Placebo-Controlled Trial in Pediatrics.Neuropaediatrics, 41, 223-227. 12
  11. Vinkers, C. H., Klanker, M., Groenink, L., Korte, S. M., Cook, J. M., Van Linn, M. L., Hopkins, S. C. & Oliver, B. (2009) Disassociating anxiolytic and sedative effects of GABA-Aergic drugs using temperature and locomotor responses to acute stress.Psychopharmacology, 204, 299-311. 7
  12. Whyte, J. & Myers, R. (2009) Incidence of Clinically Significant Responses to Zolpidem Among Patients with Disorders of Consciousness: A Preliminary Placebo Controlled Trial.American Journal of Physical Medicine & Rehabilitation, 88, 410-418. 8

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