Clinical and brain SPECT scan response to zolpidem in patients after brain damage.

UNLABELLED: 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 99mTcHMPAO 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 99mTcHMPAO 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.

Drug induced arousal from the permanent vegetative state.

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.

Effect of zolpidem on brain injury and diaschisis as detected by 99mTc HMPAO brain SPECT in humans.

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.

Cerebral blood perfusion after treatment with zolpidem and flumazenil in the baboon.

Previous studies have shown that zolpidem (CAS 82626-48-0) can lead to improved perfusion in damaged brain tissue. Zolpidem belongs to the imidazopyridine chemical class and it illicits its pharmacological action via the gamma-aminobutyric acid (GABA) receptor system through stimulation of particularly the omega 1 receptors and to a lesser extent omega 2 receptors. Previously it was reported that no cerebral blood flow effects were observed in normal baboons after treatment with zolpidem, whereas an asymmetric regional increase in cerebral blood flow was observed in a neurologically abnormal baboon. In this study, the effect of a combination of the benzodiazepine receptor antagonist flumazenil (CAS 78755-81-4) and zolpidem on brain perfusion was examined by the 99mTc-hexamethyl-propylene amine oxime (99mTc-HMPAO) split dose brain single photon emission computed tomography (SPECT). Four normal baboons and the neurologically abnormal baboon from the previous zolpidem study were examined. In the current study the asymmetric changes observed after zolpidem--only treatment in the abnormal baboon was attenuated by flumazenil intervention. A decreased brain blood flow was observed after combination treatment of zolpidem and flumazenil in the normal baboons. The involvement of the omega receptors is suggested by these results. Up- or down-regulation of omega receptors may also contribute to the observed responses in the abnormal baboon and a brain injured patient.