Abstracts

Rationale: Perampanel (PER), a unique antiepileptic drug that acts as a highly selective non-competitive antagonist of a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors, has been approved to be used as an adjunctive therapy for partial-onset and primary generalized tonic-clonic seizures in patients 12 years of age and older. Although the efficacy of PER has been emphasized in recent years, its side effects, especially behavioral outcomes, still remain an open area of research. In this study, we assessed the safety, efficacy and retention of PER in adults with refractory epilepsy. Methods: We retrospectively reviewed the first 34 outpatients who were prescribed PER as part of their antiepileptic drug regimen at Yale or Columbia Comprehensive Epilepsy Center between January 2015 and March 2016. A detailed collection of demographic and clinical data including seizure types, treatment regimen, efficacy, six- and twelve-month seizure retention and adverse effects was performed. Results: 41.2% of patients were male and 58.8% were female with a mean age of 38.8 14.3. The mean age at seizure onset was 12 11.7. The majority of patients had focal epilepsy (73.5%), 23.5% had primary generalized epilepsy and 3% had symptomatic generalized epilepsy. Patients had attempted a mean of 6.9 3.2 antiepileptic drugs (AEDs) before being started on PER. Mean duration of PER therapy was 6.1 5.3 months with an average dose of 6.8 mg /daily while on stable drug regimen. During PER treatment, patients were concurrently on 2.7 1.1 other AEDs. No patient was started on PER as monotherapy. 6- and 12-month retention rates were 58.33% (14/24) and 27.8% (5/18) for the entire cohort. There was no significant difference between focal epilepsy and primary generalized epilepsy groups for 6-month retention (63.2% (12/19) vs. 50% (2/4), p value > 0.05) but there was a statistically significant difference between the two groups for 12-month retention (46.7% (7/15) vs. 0%, p value < 0.05). 7.1% of patients became seizure free for at least 6 months. 35.3% of patients experienced an adverse effect specifically attributed to PER, with dizziness (14.7%), cognitive side effects (11.7%), ataxia (8.8%) and behavioral changes (8.8%) being the most common ones respectively; these adverse effects lead to discontinuation of PER in 29.4% of patients (8.8% dizziness, 8.8% ataxia, 8.8% behavioral changes, 8.7% cognitive side effects). There were no instances of rash. Conclusions: Our study demonstrated that adding PER, a novel alternative AED with once-daily dosing, to antiepileptic regimens can lead to clinical improvement, particularly in the case of partial epilepsy where almost half of the patients remain on the drug after one year. On the other hand, adverse effects were not unusual, especially dizziness, imbalance, cognitive and behavioral changes. Predictors and avoidance of these adverse effects warrant further studies. Funding: Eisai Pharmaceuticals, Sunovion Pharmaceuticals