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

Abstract

OBJECTIVE: To Report a Previously Unrecognized Pharmacolgic Effect of Clobazam associated with Hypothermia BACKGROUND: Clobazam is a 1-5 benzodiazepine introduced for the treatment of anxiety and agitation that has recognized antiepileptic properties with generally excelelnt tolerance without serious side effects. We report two children who utlized this drug in an appropriate dose range for treatment of complex partial seizures following infantile spasms in one case and the use of the drug in a 4 year old with developmental delay, myoclonic seizures developing progressive depression/somnolence at a dose of 0.25mg/kg/day with the decline in body temperature to 91 F requiring admission after 10 days of therapy. There are many potential sites for etmperature dysregulation including the GABAa receptor where clobazamo acts. this hypoth3ermic effect has been recognized with other benzodiazepine class drugs previosuly DESIGN/METHODS: Two children, both with severe epilepsy with prior histories of developmental delay, infantile spasms, resultant partial complex seizures were treated with clobazam in dosage ranges of 0.25mg/kg/day to 0.6mg/kg per day. Subsequent EEG monitoring and metabolic monitoring was carried out. Temperature dysregulation to 93 F in one case and 91 F in a second case in the absence of sepsis was evaluated, cessation of clobazam and reinstitution of drug was instituted. RESULTS: In both children: Recurrent hypothermia occurred after 6 days of reinstitution of clobazam in one child, withdrawl of clobazam totally in the second child resulted in normothermia for 12 months subsequently. CONCLUSIONS: Clobazam is a well known and prescribed benzodiazepine for epilepsy which may on occasion be responsible for hypothermia in therapeutic doses.