Abstracts

Rationale: Up to one third of patients with epilepsy are medically intractable, further emphasizing the need for continued development of novel AEDs with different mechanisms of action. In 2012, the FDA approved the first noncompetitive AMPA receptor antagonist Perampanel as an adjunct for partial-onset seizures. Post hoc analysis of 3 phase III trials showed a significant percentage change in the frequency of seizures when compared with placebo and a significantly larger 50% responder rate. The most common adverse effects reported were dizziness, somnolence, and headache and were mostly mild-moderate in intensity and dose dependent. However, 9.5% of patients required cessation of medication due to severe adverse effects with primary reason being dizziness. In addition, 1.2% of patients reported serious psychiatric and behavioral adverse effects, namely irritability and aggressiveness with one case of suicidal ideation, resulting in the current black box warning. Here we report our experience with Perampanel with regards to efficacy and observed adverse events. Methods: A chart review was performed on patients in our epilepsy clinic currently taking or haven taken Perampanel in the past to evaluate for efficacy of treatment and the most commonly observed adverse effects (especially psychiatric symptoms). The inclusion criteria used for data analysis was use of Perampanel for duration ≥ 28 days. Data including dosing, duration of therapy, adverse effects, concomitant AEDs, prior nonmedical treatment (i.e surgery, VNS) was obtained via chart review. Efficacy of treatment was evaluated by contacting patients and asking them to quantify decrease in seizure frequency by as <25%, 25-50% or > 50%. Results: Thirteen patients were identified; however, 2 were excluded given duration of therapy < 28 days. The remaining 11 patients (9 focal, 2 generalized epilepsies) were medically intractible with average number of concomitant AEDs being 3; all but 1 had had prior nonmedical treatment (i.e surgery, VNS). Of the 7 patients that responded to question regarding efficacy, 3 had >50% decrease, 1 had 25-50% decrease, and 3 had < 25% decrease in seizures. Preliminary results regarding tolerability suggest most tolerate well with most common side effects being dizziness and somnolence. One patient noted mood swings and irritability initially upon starting but resolved within first few weeks. Conclusions: Although our sample size is currently insufficient to determine statistical difference, in medically intractable patients there appears to be a trend towards meaningful improvement in seizure control with adjunct Perampanel and it is generally well tolerated with the most common adverse effects being somnolence and dizziness. Thus, our preliminary results regarding efficacy and tolerability appear to correspond to the previously reported post hoc analysis of the initial phase III trials; however, as our sample size and duration of therapy increases more definitive conclusions will be able to be made.