Background: Zolpidem is an omega 1 specific indirect GABA agonist that is used for insomnia, but may have efficacy in brain damage. The long term efficacy of zolpidem in the permanent vegetative state is described in three patients. Method: Two motor vehicle accident patients and one near drowning patient, all of them in the permanent vegetative state for at least three years, were rated according to the Glasgow Coma and Rancho Los Amigos scale before and after zolpidem application. Long term response to daily application of this drug was monitored for 3-6 years. Results: All patients were aroused transiently every morning after zolpidem. Glasgow Coma Scale scores ranged from 6-9/15 before to 10-15/15 after zolpidem. Rancho Los Amigos Cognitive scores ranged from I-II before to V-VII afterward. Drug efficacy did not decrease and there were no long term side effects after 3-6 years daily use. Conclusion: Zolpidem appears an effective drug to restore brain function to some patients in the permanent vegetative state.

to the editor: There is currently no effective pharmacologic treatment for spinocerebellar ataxia. We describe a family of five patients, four of whom had clinical improvement within one hour after the ingestion of zolpidem (10 mg). The diagnosis of spinocerebellar ataxia type 2 was confirmed by molecular analysis. Analysis of DNA for CAG repeat expansions in the SCA1 , 2 , 3 , 6 , and 7 genes revealed expansion of CAG repeats at the SCA2 locus.Patient 1, a 49-year-old man with titubation, dizziness, and loss of balance from the age of 34 years, had deteriorating speech and handwriting. Cerebellar signs included moderate gait ataxia, intention tremor, and dysdiadochokinesis, as well as titubation. Deep-tendon reflexes were all brisk. After treatment with zolpidem, ataxia, intention tremor, and titubation improved moderately. Pollock Park Family Practice Springs 0084, South Africa 1. Salva P, Costa J. Clinical pharmacokinetics and pharmacodynamics of zolpidem: therapeutic implications. Clin Pharmacokinet 1995;29:142-53. 2. Thomas P, Rascle C, Mastain B, Maron M, Vaiva G. Test for catatonia with zolpidem. Lancet 1997;349:702. 3. Clauss RP, Güldenpfennig WM, Nel HW, Sathekge MM, Venkannagari RR. Extraordinary arousal from the semi-comatose state on zolpidem: a case report. S Afr Med J 2000;90:68-72. 4. Cohen L, Chaaban B, Habert M-O. Transient improvement of aphasia with zolpidem. N Engl J Med 2004;350:949-50. 5.Clauss RP, Nel HW. The effect of zolpidem on brain injury and diaschisis as detected by 99mTc HMPAO brain SPECT in humans. Arzneimittelforschung (in press). Correspondence

The study investigates the effect of zolpidem (CAS 82626-48-0) on brain injuries and cerebellar diaschisis. Four patients with varied brain injuries, three of them with cerebellar diaschisis, were imaged by 99mTc HMPAO Brain SPECT before and after application of zolpidem. The baseline SPECT before zolpidem showed poor tracer uptake in brain injury areas and cerebellar diaschisis. After zolpidem, cerebral perfusion through brain injury areas improved substantially in three patients and the cerebellar diaschisis was reversed. Observations point to a GABA based phenomenon that occurs in brain injury and diaschisis that is reversible by zolpidem.

Previous reports document transient improvements after daily zolpidem (CAS 82626-48-0) in patients with brain damage. This multi-patient study evaluates the response to zolpidem in neurologically disabled patients, using 99m TcHMPAO brain SPECT scans and clinical rating scales. Method: 23 of 41 consecutive adult patients, at least 6 months after brain damage were identified as neurologically disabled patients by scoring less than 100/100 on the Barthel Index. Causes of their brain damage included stroke (n = 12), traumatic brain injury (n = 7), anaphylaxis (n = 2), drugs overdose (n = 1) and birth injury (n = 1). The selected 23 patients had a baseline 99m TcHMPAO brain SPECT scan before starting daily zolpidem therapy and a second within two weeks of therapy, performed 1 h after 10 mg oral zolpidem. Scans were designated as improved when at least two of three assessors detected improvement after zolpidem. The rest were designated non improved. After four months daily zolpidem therapy, patients were rated on the Tinetti Falls Efficacy Scale (TFES) before and after zolpidem. The TFES ratings were compared using a Wilcoxon non parametric signed rank test. Scan improvers were compared with non improvers, using a two sample t test with unequal variance. Results: Mean overall improvement after zolpidem on TFES was 11.3%, from 73.4/100 to 62.1/100 (p = 0.0001). 10/23 (43%) patients improved on SPECT scan after zolpidem. Their mean TFES improvement was 19.4% (?16.75) compared with 5.08% (?5.17) in 13/23 non improvers (p = 0.0081). Conclusion: This prospective study adds further evidence to previous reports of zolpidem efficacy in patients with established brain damage.

A recent report showed that zolpidem (CAS 82626-48-0) can lead to the arousal of a semi-comatosed patient. Zolpidem is clinically used for the treatment of insomnia. It belongs to the imidazopyridine chemical class and is a non benzodiazepine drug. It illicits its pharmacological action via the GABA receptor system through stimulation of particularly the omega 1 receptors. In this study, the effect of zolpidem on brain perfusion was examined by 99mTc hexamethyl-propylene amine oxime (HMPAO) split dose brain SPECT on four normal baboons and in one baboon with abnormal neurological behaviour. The global and regional brain perfusion was not significantly affected in the normal brains. In some regions of the abnormal baboon brain, however, there was a disproportionate increase in perfusion after zolpidem.