Clobazam in treatment of refractory epilepsy: the Canadian experience. A retrospective study. Canadian Clobazam Cooperative Group.

During the past 7 years in Canada, more than 1,300 refractory epileptic patients have been treated with clobazam (CLB) by 104 adult and pediatric neurologists. Using a standard case report, 32 neurologists, who had each treated greater than or equal to 10 patients, provided retrospective data for 877 patients. The population had the following characteristics; the percentages of children and adults were 51 and 49%, respectively; 38% of the patients were mentally retarded; the percentages for single and multiple seizure type diseases were 46 and 54%, respectively; and adults had more complex partial seizures, whereas children had more atypical absence and myoclonic types. Before clobazam, patients received an average of 2 other antiepileptic drugs (AEDs) (range 0-5 AEDs). Average dose of CLB in children was 0.87 mg/kg per day (range 0.05-3.8 mg/kg per day) and in adults 30 mg/day (range 2.5-150 mg/day). Duration of CLB therapy ranged from a few days to greater than 4 years, with 40% being treated greater than 1 year. Using Kaplan-Meier curves, we found that 4 years after starting, 40-50% of patients continued CLB. More than 40% of patients with single seizure type had at least a 50% reduction in seizure frequency (improved). At least 60% of patients with multiple seizure type had improvement in one or more seizure types, and nearly 40% of the patients had all their seizure types improved. The seizure frequency for each seizure type, except tonic, was reduced greater than 50% in 40-50% of patients and by 100% in 10-30% of patients. Twenty percent stopped CLB for poor efficacy, 4% stopped for safety-related reasons including drug interactions, and 8% stopped for both reasons. Possible side effects (predominantly somnolence) were reported by 32%; however, in only 11% were the side effects sufficiently severe to cause discontinuation of medication. "Tolerance," leading to discontinuation of CLB, was reported for 9%. Patients treated with CLB for at least 1 year were generally maintained with CLB greater than 1 year. Thus, CLB is useful in refractory epilepsy of all types, suggesting that a monotherapy trial in less severe epilepsy is now desirable.