Current status of the 1,4- and 1,5-benzodiazepines in the treatment of epilepsy: the place of clobazam.

The 1,4-benzodiazepines have a recognised place in the treatment of epilepsy. Thus, diazepam, clonazepam, and, more recently, lorazepam are used intravenously for status epilepticus. Oral clonazepam has proved useful as adjunctive therapy in generalised absence seizures, myoclonic seizures, and partial seizures. Oral nitrazepam is well known for its use in the treatment of infantile spasms with hypsarrhythmia and in the myoclonic epilepsies of childhood. Clobazam, a 1,5-benzodiazepine, has been shown in controlled studies to be superior to placebo, and in open studies it has produced an overall reduction in seizure frequency of 65%. 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 produces minimal or no cognitive impairment. The most common side-effect reported was sedation, while the overall incidence of side-effects in the open studies was 38%. In all studies reviewed, 4% of patients had to be withdrawn because of adverse reactions. In general, there are no significant interactions with other anticonvulsants, 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 36% of patients, and there is no way of predicting in which patients or when the phenomenon is likely to occur. A dose of 20 to 30 mg at night is recommended, possibly commencing at 10 mg.