Abstracts

Rationale: Clobazam is a 1,5 benzodiazepine approved for use in the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS). Patients with LGS or LGS-like seizures typically have refractory tonic/atonic epilepsy. 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. 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, which was increased to 5 mg qAM and 10 mg qPM after 1 week. 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 seven patients were initiated on treatment with clobazam with a minimum 4-week follow-up. Additional patients with < 4 week follow-up are also being followed, but not reported at time of abstract. All patients had tonic or atonic seizures requiring 2-5 daily drug regimens. 6 of 7 patients had vagal nerve stimulators implanted. Monthly seizure frequency decreased from an average of 8.7 seizures (range 1-24) to an average of 0.77 seizures (range 0-6) after initiation of clobazam therapy (see table 2). Seizure frequency was measured 8 weeks prior to clobazam initiation. Seizure frequency after clobazam initiation ranged 4-16 weeks. 3 of 7 patients were seizure free on clobazam 15 mg daily. One patient was seizure free on that dose with the exception of 1 seizure in the setting of an infection. Overall, 5 of 7 patients achieved >90% seizure frequency reduction after clobazam initiation; the remaining 2 patients achieved >75% seizure frequency reduction. With reduction in seizure frequency, use of rescue benzodiazepines was no longer required. All patients were able to be down titrated on one AED in their regimen. Conclusions: Clobazam demonstrated significant efficacy as an adjunctive treatment in tonic/atonic seizures resulting in dramatic seizure reduction. As a result, there was a decreased need for rescue benzodiazepines as well as a reduction in medication burden. Follow-up is ongoing.