Clobazam

Observational studies

In an open study 25 patients with new-onset focal and primary generalized epilepsy were treated with clobazam at a single center [ ]. After a mean follow-up of 16 months (range 7–24), 16 patients were seizure free, while five had more than a 50% reduction in seizure frequency. Sedation was the most common adverse event, reported by four patients; however, it was always mild and did not require withdrawal of clobazam. Other adverse reactions, reported in one patient each, were weight gain, ataxia, loss of short-term memory, and breakthrough seizures.

Comparative studies

In a randomized double-blind comparison of clobazam, carbamazepine, and phenytoin monotherapy in children with epilepsy, there were no differences in tests of intelligence, memory, attention, psychomotor speed, and impulsivity between clobazam and the other drugs after 6 and 12 months of therapy, suggesting that the adverse effects of clobazam on cognition and behavior may be less common than generally thought [ ]. However, the authors did not discuss a trend for some scores, particularly items in the Wechsler Intelligence Scale for Children–Revised, to improve significantly only in children taking non-benzodiazepine anticonvulsants. Moreover, many children withdrew from the study before completion of the follow-up, resulting in potential bias.

In a prospective, multicenter, double-blind comparison of clobazam with phenytoin or carbamazepine monotherapy in children with partial or generalized tonic-clonic seizures, the retention rate after 1 year did not differ, but exit due to inefficacy tended to be more common with clobazam (19% versus 11% for the other drugs combined), while exit due to adverse effects tended to be more common with carbamazepine or phenytoin (15% versus 4% for clobazam) [ ]. Although all treatments were claimed to have similar efficacy, detailed descriptions of the changes in seizure frequency and the proportion of patients who gradually achieved seizure control in each treatment group were not given. Behavioral and mood problems tended to be more common with clobazam than with the other drugs (38/119 versus 29/116). Drooling was more common with clobazam (7/119 versus 2/116), whereas rash or vomiting were more common with the other treatments (9/116 versus 4/119 and 10/116 versus 4/119, respectively). Tolerance was reported in 7.5% of patients taking clobazam, in 4.2% of those taking carbamazepine, and in 6.7% of those taking phenytoin; however, the definition of tolerance (no seizures for 3–6 months, followed by seizures sufficiently numerous to require a switch to another drug) was questionable, and no information was given about patients with seizure relapses who required an increase in dosage. Although these results suggest that clobazam is a valuable alternative to phenytoin and carbamazepine in childhood epilepsy, more precise characterization of responses would have been desirable.

Placebo-controlled studies

In a multicenter, double-blind, placebo-controlled, crossover study lasting 7 months, clobazam was compared with placebo in 129 therapy-resistant patients with epilepsy [ ]. Clobazam therapy resulted in a significant reduction in seizure frequency when compared with placebo. The most frequent adverse reactions to clobazam were drowsiness and dizziness, and the sedative effects of clobazam were less pronounced than those of other benzodiazepines.

Respiratory

Patients receiving intravenous benzodiazepines must be monitored for respiratory depression and may need artificial ventilation during intensive treatment.