Perampanel as Add-On Tx May Benefit in Severely Refractory Focal Epilepsy

The results suggest that a change in the way perampanel is initiated may be warranted.

Add-on treatment with perampanel resulted in clinically meaningful improvement in patients suffering from severely refractory focal epilepsies, according to findings presented at the AES Annual Meeting 2017.

Perampanel, an AMPA receptor antagonist, is currently approved as monotherapy or adjunctive therapy for partial-onset seizures with or without secondarily generalized seizures, and as adjunctive therapy for primary generalized tonic-clonic seizures. For this study, researchers from Italy evaluated the safety, efficacy, retention, and seizure outcomes with perampanel as add-on treatment in routine clinical practice among different patient subgroups.

Patients with drug-resistant focal epilepsy or epileptic encephalopathy (n=169) were initially treated with perampanel 2mg daily at bedtime; treatment was then increased by 2mg daily every 2 to 4 weeks. The study authors reviewed patient demographics, seizure semeiology, EEG pattern, MRI features and seizure frequency, responder rates, and adverse effects. 

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The results showed a responder rate of 29% after an average follow-up of 12 months; 8.1% of these responders were considered seizure-free. The average perampanel dose among responders was 6.38mg daily (range: 4mg to 10mg). 

“Subgroup analysis showed that retention probability was higher in TLE patients compared with extratemporal subgroup,” reported lead author Sara Casciato, IRCCS Neuromed Epilepsy Surgery Unit, Pozzilli, Italy. She added that slow titration was associated with a higher retention likelihood compared with a fast titration regimen. 

Tiredness, behavioral changes, dizziness were the most frequently occurring adverse effects, as reported in 33% of patients. 

Based on the findings, the authors concluded that the way in which perampanel is initiated by epileptologists and neurologists should be changed with a slow titration and earlier add-on period to increase the chances of the patients remaining on perampanel treatment long-term (at least 12 months).  “Further studies are warranted to explore the tolerability profile,” added Casciato. 


Casciato S, Mascia A, Quarato PP, et al. Permpanel as add-on treatment in refractory focal epilepsy and epileptic encephalopathy: Experience in routine clinical practice. Abstract 3.284.