The use of perampanel (PER) as an adjuvant treatment appears to decrease seizure relapse in patients with Lennox–Gastaut syndrome (LGS), according to a recently published study in Epilepsy.

LGS is characterized by a poor response toward pharmacologic therapeutic measures. Despite the widespread use of antiepileptic drugs such as valproic acid, there is still an urgent need for new pharmacologic alternatives, the researchers noted.

Therefore, the authors aimed to assess the effectiveness of the noncompetitive α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor antagonist PER as an adjuvant treatment for patients with LGS.

Read more about LGS prognosis

The retrospective multicenter cohort study included 87 patients with LGS that received adjuvant treatment with PER between 2019 and 2022. All of the included patients had a history of drug-resistant seizure types with onset before 18 years of age associated with cognitive and behavioral abnormalities and typical electroencephalographic findings.

The study’s primary endpoint was the assessment of time to treatment failure, defined as either PER discontinuation or the initiation of additional treatment. The secondary endpoint was time to seizure relapse.

In the included population, the average number of failed treatments was 8, and the number of concomitant treatments was 3. The titration of PER was performed at 3 different rates.

After a 36-month follow-up, treatment failure occurred in close to 60% of patients, with a median time of a year. The main reason for treatment failure was lack of effectiveness, followed by poor tolerability. However, over 60% of patients experienced a 50% reduction in drop attacks. The median time to seizure relapse was 21 months. Slow PER titration was found to decrease the risk of treatment failure.

The most common adverse effects associated with PER were behavioral, with approximately 20% of patients experiencing irritability and aggressiveness.

The authors noted that despite the encouraging results, the lack of a control group prevented them from drawing definitive conclusions.

“Despite these encouraging results suggesting how PER may represent a valuable therapeutic option for patients with LGS with inadequately controlled seizures, we cannot draw firm conclusions on its use as a first-line treatment,” the authors wrote.


Matricardi S, Cesaroni E, Bonanni P, et al. Long‐term effectiveness of add‐on perampanel in patients with Lennox–Gastaut Syndrome: a multicenter retrospective study. Epilepsia. Published online March 31, 2023. doi:10.1111/epi.17601