Zolpidem is a non-benzodiazepine drug that has selectivity for the gamma-aminobutyric acid (GABA) receptors. We experienced paradoxical effect of zolpidem in a 48-year-old male patient with hypoxic-ischemic brain injury after cardiac arrest. The patient was in stupor and could not communicate. His Glasgow Coma Scale (GCS) was E2M4V2 and Rancho Los Amigos (RLA) was grade III to IV. Zolpidem was prescribed to induce sedation but paradoxically, he became alert (GCS 15, RLA VII) and was able to communicate. The arousal lasted for 2 hours repeatedly following each administration of the medication. While he was alert, electroencephalogram showed the reversal of slow wave into beta range fast activity and F-18 flumazenil positron emission tomography (PET) showed increased GABAergic receptor activity in both frontoparietotemporal cortices. Single photon emission computed tomography (SPECT) also showed increased cerebral perfusion and reversal of cerebellar diaschisis.

Citations

Citations to this article as recorded by  

• Disorders of consciousness and pharmacotherapy: A systematic update on drugs inducing consciousness improvement
  Davide Cardile, Lilla Bonanno, Rosella Ciurleo, Rocco Salvatore Calabrò
  European Journal of Pharmacology.2025; 998: 177532.     CrossRef
• Differential regulation of K⁺-Cl⁻ cotransporter 2 (KCC2) and Na⁺-K⁺-Cl⁻ cotransporter 1 (NKCC1) expression by zolpidem in CA1 and CA3 hippocampal subregions of the lithium-pilocarpine status epileptic
  Muhammad Zulfadhli Othman, Mohd Hamzah Mohd Nasir, Wan Amir Nizam Wan Ahmad, Jafri Malin Abdullah, Ahmad Tarmizi Che Has
  Experimental Animals.2025; 74(2): 286.     CrossRef
• Speech recovery after single-dose zolpidem in two minimally conscious patients with severe traumatic brain injuries: a case report
  Yi Zhou, Kathryn A. Altonji, Ashley Kakkanatt, Brian D. Greenwald
  Brain Injury.2024; 38(5): 337.     CrossRef
• Restoring consciousness with pharmacologic therapy: Mechanisms, targets, and future directions
  Megan E. Barra, Ken Solt, Xin Yu, Brian L. Edlow
  Neurotherapeutics.2024; 21(4): e00374.     CrossRef
• Case Report: Zolpidem’s paradoxical restorative action: A case report of functional brain imaging
  Jennifer Boisgontier, Kévin Beccaria, Ana Saitovitch, Thomas Blauwblomme, Lelio Guida, Ludovic Fillon, Christelle Dufour, Jacques Grill, Hervé Lemaitre, Stéphanie Puget, Alice Vinçon-Leite, Volodia Dangouloff-Ros, Sarah Charpy, Sandro Benichi, Raphaël Lev
  Frontiers in Neuroscience.2023;[Epub]     CrossRef
• Potential Therapeutic Effects of Mi-Jian-Chang-Pu Decoction on Neurochemical and Metabolic Changes of Cerebral Ischemia-Reperfusion Injury in Rats
  Jingjing Liu, Lingling Yang, Yang Niu, Chao Su, Yingli Wang, Ruru Ren, Jianyu Chen, Xueqin Ma, ChongDe Sun
  Oxidative Medicine and Cellular Longevity.2022; 2022: 1.     CrossRef
• Pharmacologic Therapies to Promote Recovery of Consciousness
  Megan E. Barra, Brian L. Edlow, Gretchen M. Brophy
  Seminars in Neurology.2022; 42(03): 335.     CrossRef
• Postoperative Treatment of Intracranial Hypotension Venous Congestion–Associated Brain Injury With Zolpidem
  Lauren M. Desmarais, Kristen A. Milleville, Amy K. Wagner
  American Journal of Physical Medicine & Rehabilitation.2021; 100(6): e89.     CrossRef
• Multimodal neurometabolic investigation of the effects of zolpidem on leukoencephalopathy‐related apathy
  C. Delorme, I. Adanyeguh, D. Bendetowicz, I. Le Ber, A. Ponchel, A. Kas, M.‐O. Habert, F. Mochel
  European Journal of Neurology.2020; 27(11): 2297.     CrossRef
• Polypharmacy and Rational Prescribing: Changing the Culture of Medicine One Patient at a Time
  Sook Kyung Yoon, Britta Adwoa Okyere, Dale Strasser
  Current Physical Medicine and Rehabilitation Reports.2019; 7(2): 141.     CrossRef
• Paradoxical Motor and Cognitive Function Recovery in Response to Zolpidem in a Patient with Hypoxic-ischemic Brain Injury: A Case Report
  Myong Hun Hahm, Jungmin Woo
  Clinical Psychopharmacology and Neuroscience.2019; 17(3): 453.     CrossRef
• Disorders of consciousness after severe brain injury: therapeutic options
  Caroline Schnakers, Martin M. Monti
  Current Opinion in Neurology.2017; 30(6): 573.     CrossRef
• Potential benefits of zolpidem in disorders of consciousness
  Afsaneh Noormandi, Maryam Shahrokhi, Hossein Khalili
  Expert Review of Clinical Pharmacology.2017; 10(9): 983.     CrossRef