Abstracts

Rationale: In 2012, perampanel (PER), a novel, highly selective, non-competitive AMPA-type glutamate receptor, was licensed in the UK for use as an adjunctive antiepileptic drug (AED) in patients with focal-onset seizures. At that time, the only data on its use were from placebo-controlled, randomized clinical trials. A propsective audit was therefore instituted at the Epilepsy Unit at the Western Infirmary, to assess outcomes with adjunctive PER in adults with uncontrolled focal-onset seizures. At this 2-year juncture, interim results are presented. Methods: Patients were asked to record their baseline seizure frequency on stable AED dosing over a 12-week period. PER was was then introduced and titrated by 2mg every 2 weeks for patients taking hepatic enzyme inducing AEDs and every week for patients on non-enzyme inducers. Doses were increased according to efficacy and tolerability until a target PER dose of 8-12mg daily was reached, or until optimal seizure control or tolerability were achieved. Clinic visits took place every 6-8 weeks. Weight was measured throughout the audit. Patients were monitored until 1 of 4 end-points was reached: seizure freedom for 6 months or more on a given PER dose; 50% or more seizure reduction or <50% seizure reduction (marginal improvement) over 6 months compared with baseline on the highest tolerated PER dose; withdrawal of PER due to lack of efficacy, side effects, or both. Results: There are 41 patients (28M; 13F, age range 23-65 years [median 48 years]) currently participating in the audit. At baseline, monthly seizure frequency was 1-60; [median 4]), and patients received a median of 2 (range 1-4) AEDs, having previously tried 1-15 (median 3) schedules. An end-point has been reached by 34 (82.9%) patients. At this time, PER has benefitted 14 (41.2%) patients, with 2 remaining seizure-free, 3 having 50% or more reduction in seizures and 9 reporting a marginal improvement (Table 1). The median daily PER dose taken by these patients was 6mg (range 4-12mg). There was no difference in the optimum PER doses received by patients on hepatic enzyme inducing AEDs (n= 7; median daily PER dose 6mg [range 4-12mg]) compared to those receiving non-enzyme inducing AEDs (n=7; median daily PER dose 6mg [range 4-8mg]). PER was withdrawn in 20 (48.8%) patients (3 lack of efficacy; 17 side effects), the majority of whom (n=14) took 4mg daily (range 4-12mg daily). One other patient succumbed to SUDEP. Common side effects leading to PER withdrawal included nausea, vomiting, ataxia and depression (Table 2). Seven (17.1%) patients withdrew due to neuropsychiatric side effects. In those patients who had their weight monitored, compared with baseline values, weight was unchanged in 9 patients, 5 patients lost weight and 7 patients gained weight at their end-point. Median weight change was 0kg (range -19.1 - +7.9kg). Weight gain was the cause of PER withdrawal in 1 patient. Conclusions: Adjunctive PER is useful in patients with uncontrolled focal-onset seizures, often at low doses, and regardless of concomitant AED treatment. Neuropsychiatric side effects were a common reason for PER withdrawal.