The place of clobazam in the treatment of epilepsy: An update

Abstract

The 1,4-benzodiazepines have a recognized place in the treatment of epilepsy, mainly in status epilepticus, as adjunctive therapy in refractory epilepsy, in hypsarrythmia and in myoclonic epilepsy. Clobazam, the only marketed 1,5-benzodiazepine, has been shown in eight controlled studies involving 291 patients to be significantly superior to placebo, while in 35 open studies embracing 2259 patients, it has produced an overall reduction in seizure frequency of 65 per cent, with some 18 per cent of patients being rendered seizure free. The main indication for its use is as oral adjunctive therapy in refractory epilepsy. It has a rapid onset of action, is well tolerated, and many studies indicate it has a psychotropic action and/or produces minimal, or no cognitive impairment. The most common side-effect reported is transient sedation, while the overall incidence of adverse effects in the open studies is 38 per cent. In the controlled investigations 4 per cent of patients had to be withdrawn because of adverse side-effects, while in the open studies the figure was 9 per cent. In general, there are no significant interactions with other antiepileptic drugs, although changes in a few have been described. Withdrawal seizures can occur and require gradual termination of clobazam. The main disadvantage of clobazam is the development of tolerance, which develops in approximately 32 per cent of patients, and there is no way of predicting when the phenomenon is likely to occur nor in which individuals. A dose of 20 to 30 mg given preferably at night is recommended, possibly commencing at 10 mg.