RESUMEN
OBJECTIVE: The objective of this study was to evaluate the efficacy and tolerability of perampanel (PER) in late adjunctive treatment of focal epilepsy. We assessed outcomes 1) according to patients' clinical profiles and the broad mechanism of action (MoA) of concomitant antiepileptic drugs (AEDs) and 2) the effects of PER on adverse events, irritability, mood, and quality of life (QOL). METHODS: Consecutive patients commenced on PER at two epilepsy centers in Melbourne, Australia were identified. A nested cohort underwent detailed prospective assessment, while the remainder were retrospectively analyzed. Six- and 12-month efficacy endpoints were at least a 50% reduction in seizure frequency (responders) and complete seizure freedom. The prospective cohort underwent standardized validated questionnaires at 0, 1, 3, 6, and 12â¯months using the modified semi-structured seizure interview (SSI), Liverpool Adverse Events Profile (LAEP), Quality of Life in Epilepsy-Patient-Weighted (QOLIE-10-P), Neurological Disorders Depression Inventory Epilepsy (NDDI-E), and an Irritability Questionnaire. RESULTS: One hundred sixty patients were followed for a median of 6â¯months: the mean number of prior AEDs was 6, 99% had drug-resistant epilepsy, and 72% had never experienced a prior seizure-free period of at least 6â¯months (=continuously refractory epilepsy). Perampanel was associated with responder and seizure freedom rates of 30.6% and 9.4% at 6â¯months and 19.4% and 4.4% (5.6% adjusted for the titration period) at 12â¯months. Having "continuously refractory epilepsy" was associated with a reduced likelihood of seizure freedom at 6â¯months (5% vs. 30%; pâ¯=â¯0.001) and 12â¯months (3% vs. 13%; pâ¯=â¯0.058). Quality of Life in Epilepsy-Patient-Weighted, irritability, and NDDI-E showed mean improvement at 6â¯months from baseline. SIGNIFICANCE: Even when used as late add-on adjunctive therapy in patients with highly refractory focal epilepsy, PER can result in 12-month seizure freedom of 5.6%. The likelihood of seizure freedom was associated with prior "continuous medication refractoriness". Six months after introduction of PER patients reported improved mood, QOL, and decreased irritability.