Rationale:
Cenobamate is an anti-seizure medication approved by the FDA in November 2019 for the treatment of refractory focal epilepsy in patients over 18 years of age. Limited case series indicate more broad-spectrum efficacy for other types of seizures and epilepsy syndromes. Felbamate, another anti-seizure medication that is FDA-approved for the treatment of Lennox-Gastaut Syndrome (LGS), has chemical similarity to cenobamate, suggesting that cenobamate might share this capability. Because most patients with LGS continue to have seizures despite aggressive combination therapy, assessment of novel medications with promise for efficacy should be explored to optimize seizure control, possibly with more favorable side effect profiles.
Methods:
Patients with LGS treated with cenobamate by a single epilepsy provider were included in this study, conducted by retrospective chart review. Data included patient age and weight, number of previously failed medications, duration of cenobamate therapy, dose at last visit, concomitant medications at the start of treatment compared to the last visit, reported side effects, and seizure response. Seizure response was stratified by the following categories based on the change in seizure frequency from the start of treatment to the last visit: (1) 100% control, (2) >90% decrease, (3) >75 but < 90% decrease, (4) >50 but < 75% decrease (5) sz decreased but not quantified, (6) sz unchanged, and (7) sz increased.
Results:
Thirty-six patients with LGS (69.4% male, median age 17.0 years, age range 1-27 years) received cenobamate therapy. The median age at start of treatment was 15.5 years with median duration of therapy of 17.0 months at a median dose of 150 mg (25-400 mg). Prior to cenobamate, patients failed a median of eight treatments. Concomitant medications decreased by four in three patients, three in three patients, two in five patients, and one in 14 patients while nine patients had no change in concomitant medication and two patients added one medication. Fifteen of 36 patients reported no side effects, 16/36 reported sleepiness, and other adverse effects including lethargy, aggressiveness, poor appetite, ataxia, dizziness, and drooling occurred in less than 10%. Three patients were sz-free. Seizures decreased by >90% in 10 patients, >75-90% in 5 patients, and >50-75% in five patients; eight reported less frequent sz but were not quantifiable, three had no change in sz frequency, and two reported increased seizures.
Conclusions:
In this chart review, 85% of patients experienced a reduction in seizure frequency after addition of cenobamate, including seizure freedom in three patients, and >75% reduction in half of the group, indicating promise for efficacy in this complicated epilepsy syndrome. Additional prospective studies of cenobamate treatment with diligent seizure diary tracking will clarify its efficacy in patients with LGS. Funding: N/A