Table I.
Pharmacological studies on zolpidem in post-comatose patients with disorders of consciousness.
| Type of study | n (etiology) | Diagnosis | Time since insult | Dose | Main results | MRI or CT of zolpidem responders |
|---|---|---|---|---|---|---|
| Williams et al., 2013 | ||||||
| EEG case study | 3 (TBI, stroke, TBI/hypoxic) | MCS | 5, 6, 9 y | 10 mg | Behavioral improvements: verbal fluency, functional use of objects, functional communication. EEG: ↓ of power and coherence at ∼6–10 Hz and ↑ in power at ∼15–30 Hz. Changes in brain metabolism (PET): ↑ in anterior forebrain with the largest ↑ in the lateral frontal cortex |
Unavailable |
| Du et al., 2013 | ||||||
| Cohort study using SPECT | 127 [brain contrecoup contusion, primary brainstem injury, space-occupying brain compression injury and secondary brainstem injury] | VS/UWS (N.B.: no behavioral standard) | Unavailable | 10 mg | ↑ cerebral state index, ↑ cerebral perfusion, ↓ burst suppression in contrecoup contusion and space-occupying compression group. No changes in primary and secondary brainstem injury groups | Unavailable |
| Machado et al., 2011 | ||||||
| Case study | 1 (stroke) | VS/UWS | 5 y | 10 mg | Signs of arousal (eye movements and yawns), heart rate ↑, EEG changes from subdelta band to the lower delta frequency range | Lesions in rostral part of the pons, mesencephalon and both thalami |
| Snyman et al., 2010 | ||||||
| Double-blind placebo-controlled randomized trial | 3 pediatrics (1 TBI) | VS/UWS | 2, 14, 13 y | 0.14-0.2 mg/kg | No change of RLAS scores, ↑ CNCS scores (reduced responsiveness) | (No responder) |
| Whyte & Myers, 2009 | ||||||
| Multi-centric, double-blind, randomized study | 15 (8 TBI) | VS/UWS, MCS | 3 m–23 y | 10 mg | 1 responder to treatment (VS/UWS to MCS), ↑ CRS-R score, visual pursuit, response to command | Bilateral temporal lobe contusion, intraventricular hemorrhage |
| Cohen & Duong, 2008 | ||||||
| Case study | 1 (anoxic) | MCS | 8 m | 5–20 mg | ↑ lucidity, ↑ interactions, ↑ verbal and social responses | Unavailable |
| Shames & Ring, 2008 | ||||||
| Case study | 1 (anoxic) | MCS | 18 m | 10 mg | ↑ lucidity, ↑ RLAS score, ↑ verbal communication, reading, counting, verbal production, self-feeding | Mild ventricular dilatation |
| Singh et al., 2008 | ||||||
| Double-blind case study | 1 (TBI) | MCS | 4 y | 10 mg | No effect on tests with instructions which ↑ in complexity | (No responder) |
| Lo et al., 2008 | ||||||
| Double-blind case study | 2 (anoxic) | VS/UWS | ±1 m | 10 mg | No arousal improvement, no recovery of consciousness, no ↑ GCS score | (No responder) |
| Brefel-Courbon et al., 2007 | ||||||
| Double-blind, placebo-controlled randomized case study | 1 (anoxic) | MCS | 2 y | 20 mg | ↑ arousal, ↑ motor and neuropsychological performance (functional communication, eating, walking, reading and repeating words) | Unavailable |
| Clauss & Nel, 2006 | ||||||
| Case studies | 3 (2 TBI) | VS/UWS | 3–5 y | 10 mg | ↑ rousal, ↑ GCS and RLAS scores | Unavailable |
| Clauss et al., 2000 | ||||||
| Case study | 1 (TBI) | ‘Semi-comatose’ | 3 y | 10 mg | Verbal response after 15 min, talking, answering simple questions, spontaneous interaction, counting, writing | Hemorrhage in left lentiform nucleus, thalamus and cerebellar peduncles. Intra-ventricular blood in occipital horn of lateral ventricles, lesion in brainstem |
Abbreviations: n=number of patients; TBI=traumatic brain injury; VS/UWS=vegetative state/unresponsive wakefulness syndrome; MCS=minimally conscious state; ↑=increase; ↓=decrease; y=year(s); m=month(s); EEG=electroencephalogram; SPECT=single photon emission computed tomography; CRS-R=Coma Recovery Scale–Revised; RLAS=Rancho Los Amigos Scale; GCS=Glasgow Coma Scale; CNCS=Coma/Near Coma Scale; PET=positron emission tomography
Abbreviations: n=number of patients; TBI=traumatic brain injury; VS/UWS=vegetative state/unresponsive wakefulness syndrome; MCS=minimally conscious state; ↑=increase; ↓=decrease; y=year(s); m=month(s); EEG=electroencephalogram; SPECT=single photon emission computed tomography; CRS-R=Coma Recovery Scale–Revised; RLAS=Rancho Los Amigos Scale; GCS=Glasgow Coma Scale; CNCS=Coma/Near Coma Scale