Profound Hypothermia Secondary to Clobazam Use in Epilepsy: A Novel Association


Clobazam, a 1-5 benzodiazepine, was introduced in the 1970s for the treatment of anxiety and agitation. Antiepileptic properties were recognized, and efficacy in a number of epilepsy syndromes was demonstrated in humans, with good tolerance. Recent reviews are generally favorable, with a relative minimum of medication-related side effects. However, a number of benzodiazepines have been associated with causing hypothermia. To date, this side effect has not been reported with clobazam. We report two cases of profound hypothermia associated with the use of this medication for the treatment of epilepsy. Both children had significant cerebral dysgenesis and were developmentally impaired, but neither had experienced hypothermia before. Temperature dysregulation was resolved with medication withdrawal after an extensive work-up for alternative causes. Hypothermia should be considered as a possible side effect of clobazam, although the exact mechanism is unknown. Appropriate monitoring of temperature is appropriate, and precautions should be offered by caregivers.

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DiFazio, M. , Lavenstein, B. and Demarest, S. (2014) Profound Hypothermia Secondary to Clobazam Use in Epilepsy: A Novel Association. Neuroscience and Medicine, 5, 15-19. doi: 10.4236/nm.2014.51003.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Birkmayer, W. (1979) Clinical Experiences with Clobazam. British Journal of Clinical Pharmacology, 7, 121S-122S.
[2] Fielding, S. and Hoffmann, I. (1979) Pharmacology of Anti-Anxiety Drugs with Special Reference to Clobazam. British Journal of Clinical Pharmacology, 7, 7S-15S.
[3] Borland, R.G. and Nicholson, A.N. (1975) Immediate Effects on Human Performance of a 1,5-Genzodiazepine (Clobazam) Compared with the 1,4-Benzodiazepines, Chlordiazepoxide Hydrochloride and Diazepam. British Journal of Clinical Pharmacology, 2, 215-221.
[4] Barzaghi, F., Fournex, R. and Mantegazza, P. (1973) Pharmacological and Toxicological Properties of Clobazam (1-Phenyl-5-methyl-8-chloro-1,2,4,5-tetrahydro-2,4-diketo-3H-1,5-benzodiazepine), a New Psychotherapeutic Agent. Arzneimittelforschung, 23, 683-686.
[5] Gastaut, H. and Low, M.D. (1979) Antiepileptic Properties of Clobazam, a 1-5 Benzodiazepine, in Man. Epilepsia, 20, 437-446.
[6] Wheless, J.W. and Phelps, S.J. (2013) Clobazam: A Newly Approved but Well-Established Drug for the Treatment of Intractable Epilepsy Syndromes. Journal of Child Neurology, 28, 219-229.
[7] Clark, S.M. and Lipton, J.M. (1981) Effects of Diazepam on Body Temperature of the Aged Squirrel Monkey. Brain Research Bulletin, 7, 5-9.
[8] Whitelaw, A.G., Cummings, A.J. and McFadyen, I.R. (1981) Effect of Maternal Lorazepam on the Neonate. British Medical Journal (Clinical Research ed.), 282, 1106-1108.
[9] Echizenya, M., Mishima, K., Satoh, K., et al. (2004) Enhanced Heat Loss and Age-Related Hypersensitivity to Diazepam. Journal of Clinical Psychopharmacology, 24, 639-646.
[10] Muthu, S., Prasath, M. and Arun Balaji, R. (2011) Experimental and Theoretical Investigations of Spectroscopic Properties of Clobazam. Recent Research in Science and Technology, 3, 127-135.
[11] Clapham, J.C. (2012) Central Control of Thermogenesis. Neuropharmacology, 63, 111-123.
[12] Dimitrov, E.L., Kim, Y.Y. and Usdin, T.B. (2011) Regulation of Hypothalamic Signaling by Tuberoinfundibular Peptide of 39 Residues Is Critical for the Response to Cold: A Novel Peptidergic Mechanism of Thermoregulation. Journal of Neuroscience, 31, 18166-18179.
[13] Sankar, R. (2012) GABA(A) Receptor Physiology and Its Relationship to the Mechanism of Action of the 1,5-Benzodiazepine Clobazam. CNS Drugs, 26, 229-244.
[14] Irvine, R.E. (1966) Hypothermia Due to Diazepam. British Medical Journal, 2, 1007.
[15] Hostler, D., Northington, W.E. and Callaway, C.W. (2009) High-Dose Diazepam Facilitates Core Cooling during Cold Saline Infusion in Healthy Volunteers. Applied Physiology, Nutrition, and Metabolism, 34, 582-586.
[16] Dowden, J., Reid, C., Dooley, P. and Corbett, D. (1999) Diazepam-Induced Neuroprotection: Dissociating the Effects of Hypothermia Following Global Ischemia. Brain Research, 829, 1-6.
[17] Kurz, A., Sessler, D.I., Annadata, R., et al. (1995) Midazolam Minimally Impairs Thermoregulatory Control. Anesthesia & Analgesia, 81, 393-398.
[18] Vidal, C., Suaudeau, C. and Jacob, J. (1983) Hyper- and Hypothermia Induced by Non-Noxious Stress: Effects of Naloxone, Diazepam and Gamma-Acetylenic GABA. Anesthesia & Analgesia, 33, 587-590.
[19] Zachariah, S.B., Zachariah, A., Ananda, R. and Stewart, J.T. (2000) Hypothermia and Thermoregulatory Derangements Induced by Valproic Acid. Neurology, 55, 150-151.
[20] Hess, P.E., Snowman, C.E. and Wang, J. (2005) Hypothermia after Cesarean Delivery and Its Reversal with Lorazepam. International Journal of Obstetric Anesthesia, 14, 279-283.

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