Perampanel seems safe and efficient for the treatment of some patients with rare genetic epilepsies, including Lennox-Gastaut syndrome (LGS), according to a new study published in the journal Epilepsia.  

The treatment led to high seizure reduction, which was maintained, and higher efficacy in certain genetic variants, including SCN1A, suggesting a targeted effect related to glutamate transmission.

Read more about the etiology of LGS

To identify possible subgroups of genetic epilepsy for which perampanel may be highly efficient, a team of researchers led by Angelo Russo, MD, from the Istituto delle Scienze Neurologiche di Bologna in Italy, collected data from a large rare genetic epilepsy cohort treated with the medication.

The team analyzed 137 patients, who were 2 months to 61 years of age and had 79 different etiologies. 

The mean dosage of perampanel was 6.45 mg, and the mean treatment period was 2  years, but almost half (44.9%) of patients were treated for more than 2  years. 

Of these 137 patients, 71% were responders, and 67.4% continued therapy. 

The mean reduction in seizure frequency was 56.61%, and a little less than half (43.5%) of patients sustained more than 75% reduction in the frequency of seizures. Almost a third (27.5%) of patients had a more than 90% reduction in the frequency of seizures. 

The genes that showed a high treatment efficacy were SCN1A, GNAO1, PIGA, PCDH19, SYNGAP1, POLG1, POLG2, and NEU1.

Perampanel is an antiseizure medication that has α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist properties. It, therefore, may have a targeted effect in genetic epilepsies with glutamate receptor overactivation, among others.

LGS is a type of epilepsy associated with a loss of γ-aminobutyric acid inhibition in some cases due to a mutation in the SCN1A gene. However, most cases are secondary to an underlying structural abnormality of the brain.


Nissenkorn A, Kluger G, Schubert-Bast S, et al. Perampanel as precision therapy in rare genetic epilepsies. Epilepsia. Published online February 2, 2023. doi:10.1111/epi.17530