Clinical Medicine Insights: Therapeutics

Recent developments in the treatment of seizure disorders have been focused on medications with novel mechanisms of action. One such medication is perampanel, a first-in-class, noncompetitive, α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor antagonist recently approved for the adjunctive treatment of partial seizures in patients 12 years of age and older when other antiepileptic medications have failed. The drug has demonstrated efficacy in several clinical trials, and appears to exert its anti-seizure activity in a dose-dependent manner. The drug has a half-life of approximately 105 hours suggesting the medication might be a logical option for individuals who have difficulty with adherence to medications that require multiple daily doses. Because of changes in serum concentration when enzyme-inducing antiepileptic drugs are employed concurrently, escalations in the initial dose of perampanel are recommended. Adverse events reported with perampanel use tend to be mild to moderate. However, psychiatric side-effects, including hostility and aggressive behavior, have been noted in some patients resulting in the inclusion of a warning on the Food and Drug Administration (FDA) approved labeling.