Abstracts

Rationale: Because of the concerns of drug interactions between clobazam and cenobamate, and because many of my refractory patients had a large baseline drug burden, I sought to investigate whether the addition of low dose clobazam in my cenobamate patients who did not achieve adequate seizure control, would be helpful in obtaining better seizure control without excessive side effects.

Methods: All twelve patients in this report were drawn from my clinical practice. Consent obtained from either patients or their legal guardians. All patients were on baseline cenobamate, 5 at 250mg, 6 at 300mg, one at 350mg. Ages ranged from 20-57, 30 years of szs on average, 8 males and 4 females. Five had Lennnox Gastaut, four were idiopathic, two had cerebral palsy, and one had Aicardi syndrome. All had focal epilepsy. At baseline, beyond their cenobamate, patients were on up to 6 other seizure meds. None had been on clobazam previously. Baseline seizure frequency came from two months prior to start of clobazam. Clobazam was initiated at 5mg at night but was reduced for side effects or raised for better seizure control. The patients were followed four months and at that point the clobazam doses were recorded, along with seizure frequency from last two months.

Results: Baseline seizure frequency ranged from 1-45 seizures per month with a mean of 14 per month. At four months the clobazam doses were as follows: one at 5mg every third day, seven at 5mg every other day, one at 5mg every day, and three at 10mg every day. At four months, six patients were seizure free, three had one seizure per month, one had two seizures per month, one had three seizures per month, and one had four seizures per month. No patient worsened in terms of seizure control. Four experienced drowsiness, two experienced dizziness, all of which improved with reduction of clobazam and/or concomitant medications, especially clonazepam which was reduced in two patients, and discontinued in two others. All patients were able to continue clobazam throughout the four months. The study was too short to see dramatic reductions of the baseline medication burden, but that is an ongoing goal in those patients who had the most dramatic reduction of seizures.

Conclusions: Refractory patients with epilepsy have many unmet needs, most due to lack of seizure control, which increases their risk of injury, SUDEP, limit potential for employment, and much more. At the same time, the increased medication burden these patients often harbor increase chances of side effects significantly. The focus of this observational study with adding clobazam to cenobamate in refractory patients was to see if such an addition was beneficial and whether the side effects of the combination could be safely managed, especially in patients who were on several other anti-seizure medications. Although this study is not blinded the results are consistent enough to support the following conclusion: The addition of low dose clobazam to refractory epilepsy patients on significant doses of cenobamate can significantly improve seizure control, but that this addition must be done at much lower doses than most are used to using with clobazam and requires close monitoring.

Funding: None