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 In all studies reviewed, 4% of patients had to be withdrawn because of adverse reactions.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.