Clobazam in the treatment of epilepsy

Clobazam, a 1,5-benzodiazepine, is a potent anticonvulsant but the development of tolerance limits its use. It has been suggested that low dose clobazam may prevent or delay the onset of tolerance. This study aimed to assess, by an open trial, the anticonvulsant activity of low dose clobazam in 11 adult patients with frequent intractable seizures. Serum clobazam and N-desmethylclobazam levels were assayed and correlated with clinical effect, adverse effects, drug dose and the development of tolerance. Clobazam was given in addition to conventional antiepileptic therapy, beginning with a dose of 20 mg at night. A 50% or greater reduction in the frequency of seizures was noted, at least transiently, in all patients. In 8 of the 11 patients there was a subsequent deterioration in control of epilepsy and in all patients this relapse occurred within 3 months of commencing treatment. There was a relationship between plasma concentrations of N-desmethylclobazam (but not of clobazam) and therapeutic and toxic effects. Tolerance was not associated with a fall in plasma levels. It is concluded that clobazam is of limited value as a long term anticonvulsant and that the high incidence of tolerance is not reduced by the use of low doses.