More than 20
antiepileptic drugs (AEDs) are currently available for the medical treatment of
epilepsies. However, still about 30% of all
epilepsies have a
drug-resistant course. Even worse, in the case of some
epilepsy syndromes, freedom from
seizures is almost never achieved. Therefore, new treatment options are still necessary, especially if theoretical concepts such as a new mode of action offer new horizons.
Perampanel 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 three 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. Phase III trials showed superiority of adjunctive
perampanel over placebo consistently in the range between 4 and 12 mg.
Dizziness and
somnolence were by far the leading adverse events. This review covers the clinical trial evidence but also clinical experience with
perampanel after launch according to observational studies.