Abstracts

Rationale: Near 30% of all epilepsies are drug-resistant. Therefore, new treatment options are still necessary, especially those based on theoretical concepts such as a new mode of action. Perampanel is a new therapeutic option with a new mode of action: is the first-in-class orally active, selective, noncompetitive antagonist of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. The pharmacokinetic profile offers once-daily dosing in the evening as the best route of administration. According to the results of pivotal placebo-controlled, double-blind phase III trials that investigated perampanel as an adjunctive AED in adult and adolescent patients from age 12 years who had ongoing focal epileptic seizures despite receiving one to three AEDs, perampanel has been widely licensed and introduced as a new promising AEDMethods: We analyzed clinical course of the first patients treated with adjunctive perampanel in our two centers, considering an observational period of 6 months. Treatment was always started with 2 mg of perampanel once daily. After each 2 mg increase we asked patients to wait for 4 weeks because our experience in single cases was that a dose of 4 mg could have a beneficial effect already, and that sometimes adverse effects were prevented by a slower titration period. Efficacy data were evaluated for the period of the last 3 months. Retention rate was assessed monthly during the first 6 months of observation. In the case of discontinuation the reason was stated.Results: 13 patients initially included. Age between 16 and 64 years. In most cases epilepsies were symptomatic. 2 patients were on one baseline AED, 6 were on two AEDs, and 5 were on three or more AEDs. At cutoff maintenance dosages varied widely. Mean dosage was 6.6 mg (range 4–10 mg). Considering last 3 months of observation compared with baseline, 4 patients were responders (at least 50 % reduction) but not seizure-free. 2 more were seizure-free (one of them with only 4 mg / day of Perampanel). Adverse events were reported in 7 patients: somnolence, irritability, aggressiveness and dizziness, ataxia and falls, cognitive slowing and depression were reported. Retention rate after 6 months was 77 % (10/13). Side effects leading to reduction or discontinuation of perampanel disappeared after proper adjustment was done.Conclusions: Perampanel is a new therapeutic option with a new mechanism of action and easy daily dosing due to long half-life. Although it has been described most patients will need higher dosages, in some patients efficacy and/or adverse events may become apparent at relatively low dosage. Thus we think in clinical practice adjunctive perampanel means another opportunity to use a new mode of action AED which can lead to significant improvement even at low dosage with easy to deal side effects. Our experience is however, limited to an observational follow-up of perampanel in a small group of patients, but we think it can be useful as a tool for daily outpatient clinical practice