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Perampanel: Another Choice for Patients with Idiopathic Generalized Epilepsy who Have Tonic–Clonic Seizures

Commentary Idiopathic generalized epilepsy syndromes are presumably genetic and manifested by multiple seizure types, including primary generalized tonic–clonic, absence, and myoclonic seizures. Primary generalized tonic–clonic seizures may precipitate numerous adverse outcomes, such as seizure-related injuries and SUDEP. The primary treatment of these seizures is antiepileptic drug (AED) therapy. In contrast to focal seizures, surgical therapies. Unfortunately, even though AED therapy is the mainstay of treatment, AED options are limited. Since 1993, 15 AEDs have been approved in the United States, and yet among these new generation AEDs, only three—lamotrigine, levetiracetam, and topiramate—have received approval for the treatment of primary generalized tonic–clonic seizures. These AEDs have all demonstrated efficacy in randomized double-blind, placebo-controlled trials of adjunctive treatment for drug resistant primary generalized tonic–clonic seizures (1). Evidence also supports the use of valproic acid (1). Clearly, we need more options to treat refractory generalized tonic–clonic seizures in idiopathic generalized epilepsy. Perampanel, as reported by French and colleagues, is a promising option as adjunctive therapy. Perampanel, a noncompetitive α-amino-3hydroxy-5methy-4-isoxazole-propionic acid (AMPA) receptor antagonist, is structurally novel, and has been studied extensively in both preclinical studies and in clinical trials of focal seizures (2). It has antiepileptic properties in multiple animal models of seizures and epilepsy including in the rat amygdala kindling model. Efficacy in this model suggests that perampanel may be able to treat primary generalized seizures. Both blinded short-term and open-label long-term extension trials have revealed significant reductions in focal seizures in doses ranging from 4 to 12 mg per day. Reported adverse events in these trials include dizziness, somnolence, and neuropsychiatric disturbances. Perampanel as adjunctive therapy for treatment of drug resistant primary generalized tonic–clonic seizures in adults and adolescents with refractory idiopathic generalized epilepsy was investigated in a multicenter, international, double-blind, placebo-controlled, parallel-group study. Eligible subjects included patients aged 12 and older diagnosed with primary generalized tonic–clonic seizures and idiopathic epilepsy who had ≥ three primary generalized tonic–clonic seizures during Perampanel for Tonic–Clonic Seizures in Idiopathic Generalized Epilepsy: A Randomized Trial