Perampanel in routine clinical use in idiopathic generalized epilepsy: The 12‐month GENERAL study

Abstract

Summary Objective To analyze the effectiveness and tolerability of perampanel across different seizure types in routine clinical care of patients with idiopathic generalized epilepsy (IGE). Methods This multicenter, retrospective, 1‐year observational study collected data from patient records at 21 specialist epilepsy units in Spain. All patients who were aged ≥12 years, prescribed perampanel before December 2016, and had a confirmed diagnosis of IGE were included. Results The population comprised 149 patients with IGE (60 with juvenile myoclonic epilepsy, 51 generalized tonic–clonic seizures [GTCS] only, 21 juvenile absence epilepsy, 10 childhood absence epilepsy, 6 adulthood absence epilepsy, and one Jeavons syndrome). Mean age was 36 years. The retention rate at 12 months was 83% (124/149), and 4 mg was the most common dose. At 12 months, the seizure‐free rate was 59% for all seizures (88/149); 63% for GTCS (72/115), 65% for myoclonic seizures (31/48), and 51% for absence seizures (24/47). Seizure frequency was reduced significantly at 12 months relative to baseline for GTCS (78%), myoclonic (65%), and absence seizures (48%). Increase from baseline seizure frequency was seen in 5.2% of patients with GTCS seizures, 6.3% with myoclonic, and 4.3% with absence seizures. Perampanel was effective regardless of epilepsy syndrome, concomitant antiepileptic drugs (AEDs), and prior AEDs, but retention and seizure freedom were significantly higher when used as early add‐on (after ≤2 prior AEDs) than late (≥3 prior AEDs). Adverse events were reported in 50% of patients over 12 months, mostly mild or moderate, and irritability (23%), somnolence (15%), and dizziness (14%) were most frequent. Significance In routine clinical care of patients with IGE, perampanel improved seizure outcomes for GTCS, myoclonic seizures, and absence seizures, with few discontinuations due to adverse events. This is the first real‐world evidence with perampanel across different seizure types in IGE.

Efficacy and tolerability of perampanel in patients with genetic generalized epilepsy (GGE): A retrospective, single-center study from the United Arab Emirates (UAE)

“…Other real-world studies such as the one by Villanueva and colleagues [15] have reported similar results while also looking at different seizure types in GGE. Juvenile myoclonic epilepsy (JME) was the most common syndrome in their subjects at 40%, compared with 76% in the current cohort.…”

Ionotropic Glutamate Receptors in Epilepsy: A Review Focusing on AMPA and NMDA Receptors

“…On the other hand, an AMPA antagonist, perampanel, has been approved as an anti-seizure drug for focal seizures and primary generalized tonic-clonic seizures [25][26][27][28][29]. Recent preliminary observations have suggested that perampanel may be efficacious in patients with other seizure types such as myoclonic or absence seizures [30,31]. As noted above, agonists of both NMDA and AMPA receptors have been shown to elicit seizures in animal models, but clinical study results differ between the two receptor types.…”

Low-Dose Perampanel Rescues Cortical Gamma Dysregulation Associated With Parvalbumin Interneuron GluA2 Upregulation in Epileptic Syngap1+/− Mice

“…Case reports indicate that adult patients demonstrate gradual decline in cognitive abilities (21). Perampanel (PMP), an AMPA receptor (AMPAR) antagonist recently approved by the Food and Drug Administration, has shown significant promise for multiple seizure types in idiopathic generalized epilepsies, including absence seizures (22). Its use in infants with epilepsy is in clinical trial (23).…”