Clorazepate and phenobarbital as antiepileptic drugs: a double-blind study

The antiepileptic effect of clorazepate when given with phenytoin was compared, in a randomized double-blind crossover study, to the effect of the standard regimen of phenobarbital plus phenytoin in patients with partial seizures. Thirty of 42 subjects preferred the clorazepate-phenytoin regimen (p less than 0.01). The same number of subjects had fewer seizures while taking clorazepate as had fewer seizures while taking phenobarbital. However, subjects had significantly more toxicity, objective and subjective, on the phenobarbital-phenytoin regimen (p less than 0.01 in both cases). In some subjects, increased toxicity due to phenobarbital outweighed better seizure control, so that clorazepate was preferred. As an add-on antiepileptic drug, clorazepate is well tolerated, effective, and preferred by most patients to phenobarbital.