Abstracts

Rationale: Patients with seizures associated with Lennox-Gastaut syndrome (LGS) typically have refractory tonic/atonic epilepsy. Clobazam is a 1,5 benzodiazepine approved for use in the adjunctive treatment of seizures in LGS or LGS-like syndromes. Previously approved therapies, in addition to VNS, in this cohort of patients have failed to control these seizure types. The adjunctive use of clobazam was initiated in this population for the purpose of reducing frequency of atonic/tonic seizures and followed over the course of one year.Methods: Patients with cognitive delay, intellectual disability, and refractory tonic/atonic epilepsy (LGS or LGS-like syndromes) were seen in routine outpatient clinic visits. Clobazam was initiated, typically at 5 mg twice daily. Clobazam dose was increased subsequently only if the patient had breakthrough seizures. The primary outcome was reduction in seizure frequency after initiation of clobazam. Secondary outcomes included the decreased need for rescue benzodiazepines and a goal of reduction in concomitant anti-epileptic medications.Results: A total of 42 patients were initiated on treatment with clobazam with a followup ranging 2-40 months. All patients had tonic or atonic seizures requiring 2-5 daily drug regimens. 41% of patients had vagal nerve stimulators implanted. Monthly seizure frequency decreased from an average of 12.7 seizures (range 1-75) to an average of 2.9 seizures (range 0-30) after initiation of clobazam therapy. Seizure frequency was measured 8 weeks prior to clobazam initiation. Seizure frequency after clobazam initiation ranged 2-40 months. Dosage range of clobazam was 10-40 mg daily. 8 of 41 patients were seizure free on clobazam. An additional 3 patients were seizure free on clobazam with the exception of 1 seizure in the setting of an infection. Overall, 26 of 41 patients achieved >75% seizure frequency reduction after clobazam initiation; of the remainder, 10 patients had >50% seizure frequency reduction and 3 patients with >25% reduction in frequency.. With reduction in seizure frequency, use of rescue benzodiazepines was no longer required. 10 of 41 patients were able to be tapered off a concomitant AED after initiation of clobazam and an additional 28 of 41 were able have a reduction in dosage of a concomitant AED. Conclusions: Clobazam demonstrated significant efficacy as an adjunctive treatment in tonic/atonic seizures resulting in dramatic seizure reduction. Strikingly, the effectiveness of clobazam in reducing seizure frequency was maintained over long-term followup. As a result, there was a decreased need for rescue benzodiazepines, a reduction in medication burden, and subjective improvement in quality of life in this patient population.