Perampanel: Does it have broad‐spectrum potential?

Summary This article reviews the profile of perampanel, a novel noncompetitive α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazole‐propionate ( AMPA ) receptor antagonist, and its role as a potential broad‐spectrum antiepileptic drug in the treatment of epilepsy. For this narrative review, data were collected using specified search criteria. Articles reporting the evidence for perampanel's efficacy from preclinical models, phase 3 clinical studies, observational studies, and descriptive evidence were included. AMPA receptors play a key role in mediating the action of glutamate at the excitatory synapse. Preclinical research showed the AMPA receptor blockade to constitute a promising target for antiepileptic drug therapy. In animal models, perampanel proved to be protective against seizures and reduce seizure severity and duration. Four phase‐3 randomized controlled trials (3 in patients with focal seizures and one in primary generalized tonic–clonic seizures in idiopathic generalized epilepsy) have been completed. In focal (partial) onset seizures, perampanel (4, 8, and 12 mg) significantly reduced seizure frequency per 28 days (23.3%‐28.8% vs 12.8%; P  < .01) and responder rates (≥50% reduction in seizures) (28.5%‐35.3% vs 19.3%; P  < .05) compared with placebo. In primary generalized tonic–clonic seizures, perampanel 8 mg resulted in greater reduction in seizure frequency per 28 days (−76.5% vs −38.4%; P  < .0001) and responder rate (64.2% vs 39.5%; P  = .0019) than placebo. The efficacy, safety, and tolerability of perampanel have been reproduced in real‐world clinical practice, and the agent has been shown to be effective in other epilepsy syndromes. Perampanel is a potentially broad‐spectrum antiepileptic drug with a novel mechanism of action that may be a useful addition for patients with epilepsy with various seizure types. The availability of novel antiepileptic drugs for epilepsy treatment enables more individualized treatment for these patients.