Open study of clobazam in refractory epilepsy.

Clobazam is a 1,5-benzodiazepine reported to have a wide spectrum of antiepileptic activity and is associated with less neurotoxicity than the 1,4-benzodiazepines, nitrazepam and clonazepam. The effect of clobazam on seizure control and neurologic behavior was examined prospectively in 115 children (average age: 8.4 years) with intractable seizures. Eighteen children (16%) became seizure free and a further 35 (31%) demonstrated a greater than 90% decrease in seizure frequency. Tolerance to the antiepileptic effect of clobazam was observed in 30 of 79 children (38%) who demonstrated an initial improvement in seizure control. Complete tolerance was observed in 9 patients, partial tolerance in 9, and partial tolerance that responded to an increased dose of clobazam in 12. Seventy-two percent of patients reported improvement and 26% worsening in at least one parameter of neurologic function after beginning clobazam. The improvement in neurologic function correlated poorly with change in seizure control. Patients who discontinued 1,4-benzodiazepine (n = 37) had a greater improvement in attention span, alertness, balance, drooling, and mood compared to the remainder of the group. These data suggest that clobazam is effective in the treatment of children with a wide range of epilepsies and seizure types and support the clinical impression that clobazam is associated with less neurotoxicity than the 1,4-benzodiazepines.