Effectiveness and safety of perampanel monotherapy for focal and generalized tonic‐clonic seizures: Experience from a national multicenter registry

Abstract Objective To assess the effectiveness and tolerability of perampanel (PER) monotherapy in routine clinical practice for the treatment of focal onset and generalized tonic‐clonic seizures (GTCS). Methods This multicenter, retrospective, observational study was conducted in patients aged ≥12 years treated with PER as primary monotherapy or converted to PER monotherapy by progressive reduction of background antiepileptic drugs. Outcomes included retention, responder, and seizure‐free rate after 3, 6, and 12 months and tolerability throughout the follow‐up. Results A total of 98 patients (mean age = 49.6 ± 21.7 years, 51% female) with focal seizures and/or GTCS were treated with PER monotherapy for a median exposure of 14 months (range = 1‐57) with a median dose of 4 mg (range = 2‐10). The retention rates at 3, 6, and 12 months and last follow‐up were 93.8%, 89.3%, 80.9%, and 71.4%, respectively. The retention rates according to the type of monotherapy (primary vs conversion) did not differ (log‐rank P value = .57). Among the 98 patients, 61.2% patients had seizures throughout the baseline period, with a median seizure frequency of 0.6 seizures per month (range = 0.3‐26). Responder rates at 3, 6, and 12 months were 79.6%, 70.1%, and 52.8%, respectively, and seizure freedom rates at the same points were 62.7%, 56.1%, and 41.5%. Regarding the 33 patients who had GTCS in the baseline period, 87.8% were seizure‐free at 3 months, 78.1% at 6 months, and 55.1% at 12 months. Over the entire follow‐up, PER monotherapy was generally well tolerated, and only 16% of patients discontinued PER due to adverse events (AEs). Female patients were found to be at a higher risk of psychiatric AEs (female vs male odds ratio = 2.85, 95% confidence interval = 1‐8.33, P = .046). Significance PER demonstrated good effectiveness and a good safety profile when used as primary therapy or conversion to monotherapy at relatively low doses, in a clinical setting with patients with focal seizures and GTCS.