Zolpidem arousing effect in persistent vegetative state patients: Autonomic, EEG and behavioral assessment

Calixto Machado, Mario Estévez, Rafael Rodríguez, Jesús Pérez-Nellar, Mauricio Chinchilla, Philip DeFina, Gerry Leisman, Frederick R. Carrick, Robert Melillo, Adam Schiavi, Joel Gutiérrez, Maylén Carballo, Andrés Machado, Ana Olivares, Nuvia Pérez-Cruz

Research output: Contribution to journalReview articlepeer-review

21 Scopus citations


Objective. To study the Zolpidem arousing effect in persistent vegetative state (PVS) patients combining clinical evaluation, autonomic assessment by heart rate variability (HRV), and EEG records. Methods. We studied a group of 8 PVS patients and other 8 healthy control subjects, matched by age and gender. The patients and controls received drug or placebo in two experimental sessions, separated by 10-14 days. The first 30 minutes of the session were considered the basal record, and then Zolpidem was administered. All participants were evaluated clinically, by EEG, and by HRV during the basal record, and for 90 minutes after drug intake. Results. We found in all patients, time-related arousing signs after Zolpidem intake: behavioral (yawns and hiccups), activation of EEG cortical activity, and a vagolytic chronotropic effect without a significant increment of the vasomotor sympathetic tone. Conclusions. We demonstrated time-related arousing signs after Zolpidem intake. We discussed possible mechanisms to explain these patho-physiological findings regarding EEG cortical activation and an autonomic vagolytic drug effect. As this autonomic imbalance might induce cardiocirculatory complications, which we didn't find in any of our patients, we suggest developing future trials under control of physiological indices by bedside monitoring. However, considering that this arousing Zolpidem effect might be certainly related to brain function improvement, it should be particularly considered for the development of new neuro-rehabilitation programs in PVS cases. According to the literature review, we claim that this is the first report about the vagolitic effect of Zolpidem in PVS cases.

Original languageEnglish (US)
Pages (from-to)4185-4202
Number of pages18
JournalCurrent pharmaceutical design
Issue number26
StatePublished - 2014


  • Arousal
  • Autonomic
  • EEG
  • Heart rate variability
  • Persistent vegetative state
  • Zolpidem

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery


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