Perampanel, an AMPA receptor antagonist: From clinical research to practice in clinical settings

Epileptic seizures are refractory to treatment in approximately one‐third of patients despite the recent introduction of many newer antiepileptic drugs ( AED s). Development of novel AED s therefore remains a high priority. Perampanel is a first‐in‐class non‐competitive selective AMPA receptor antagonist with a unique mechanism of action. Clinical efficacy and safety of perampanel as adjunctive treatment for focal seizures with/without secondary generalization (± SG ) and primary generalized tonic‐clonic ( PGTC ) seizures have been established in five phase 3 randomized controlled trials ( RCT s), and a long‐term extension study, and perampanel is approved as monotherapy for focal seizures ± SG in the USA . In patients with focal seizures ± SG , add‐on perampanel resulted in median percent reduction in seizure frequency 23.3%‐34.5% and ≥50% responder rate 28.5%‐37.6%; in PGTC seizures, these results were 76.5% and 64.2%, respectively. Efficacy among adolescents (reduction in seizure frequency 34.8%‐35.6%; ≥50% responder rate 40.9%‐45.0%) and elderly people (reduction in seizure frequency 12.5%‐16.9%; ≥50% responder rate 22.2%‐42.9%) is similar to those in adults, and results remain comparable between Asian (reduction in seizure frequency 17.3%‐38.0%) and global populations. Perampanel has been extensively studied in real‐world clinical practice, with similar efficacy and safety results to the RCT s (≥50% responder rate 12.8%‐75.0%; adverse events of somnolence/sedation, dizziness, ataxia, and behavioral changes). Real‐world observational studies suggest that perampanel tolerability can be improved by slow titration (2 mg every 2‐4 weeks), and bedtime administration can mitigate somnolence and dizziness. Counseling about the potential for behavioral changes and close monitoring are recommended.