Antiepileptic effect and serum levels of clorazepate on children with refractory seizures.
Clorazepate dipotassium is rapidly decarboxylated to yield desmethyl diazepam. The antiepileptic effect of clorazepate was studied in 29 epileptic children with refractory seizures. Their ages were ranged from one year 9 months to 20 years (mean 11 years 6 months). Serum clorazepate levels were also determined in 16 patients. The mean initial dose was 0.91 mg/kg/day, and the dose was increased up to 3 mg/kg/day. Within several days after initiation of clorazepate therapy, a decrease in seizure frequency was seen in patients in whom clorazepate was effective. Excellent results (decrease in seizure frequency by more than 80%) were obtained in 7 patients (24.1%), a moderate improvement with a 50 to 80% decrease was seen in 7 patients (24.1%), and a partial improvement with less than 50% decrease was seen in 7 patients (24.1%). No benefit was seen in 8 patients (27.7%). Serum clorazepate levels in patients with excellent results were 31 to 77 ng/ml (mean 55 ng/ml), those in patients with a moderate improvement were 130 to 225 ng/ml (mean 163 ng/ml), and those in patients with a partial improvement were 142 to 518 ng/ml (mean 273 ng/ml). Serum clorazepate levels in patients with no benefit were 34 to 97 ng/ml (mean 56 ng/ml). There was no direct relationship between serum clorazepate levels and clinical response. The results of this study indicate the efficacy of clorazepate for epileptic children with refractory seizures.