Perampanel Demonstrates Effectiveness in Treating Comorbid Epilepsy and Migraine

Claudio Liguori, MD

Perampanel (Fycompa; Eisai), an FDA-approved antiseizure (ASM) medication, significantly reduced epileptic seizures, migraine attacks, and the use of monthly rescue migraine medications over a 12-month stretch in a cohort of patients with comorbid epilepsy and migraine.¹

For years, the mechanisms underlying the association of epilepsy and migraine have not been fully understood; however, some common pathophysiological processes in migraine and epilepsy have been recognized.^2,3 In this observational study, senior author Claudio Liguori, MD, neurologist, Epilepsy Center, University of Rome, and colleagues aimed to confirm the effectiveness of perampanel in 31 enrolled patients with comorbid epilepsy and migraine.

The mean age of the cohort was 40.13 years (±13.13) and was mostly made up of women (n = 21; 67.7%). Fourteen patients (45.2%) started perampanel with 1 concomitant ASM and 17 patients started the study drug in association with 2 ASMs (54.8%).

At 12 months, most patients (n = 27; 87.1%) retained treatment, with 2 patients discontinuing due to lack of efficacy and 2 due to adverse events (AEs). Treatment with perampanel over a year stretch resulted in seizure freedom for 11 patients, while 7 experienced at least 75% reductions, 3 with at least 50%, 1 with at least 25%, and 5 that remained unchanged. There was also a statistically significant difference in epileptic seizure frequency means across baseline and the 6- and 12-month follow-up visits (X2 = 33.767; P <.001).

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Perampanel showed significant impact on reducing migraine as well, with 10 patients not experiencing a single migraine attack throughout the 12-month period. Additionally, 7 participants reported at least 75% reduction in migraine attacks, 5 had reductions of at least 50%, 4 had a reduction of at least 25%, and 1 patient remained unchanged.

"The findings of the present study are promising and highlight the good effectiveness of [perampanel] in both reducing epileptic seizures and migraine attacks in patients with comorbid epilepsy and migraine," Liguori et al wrote.¹ "Future studies with larger samples are needed to determine if [perampanel]may be an effective option to treat patients with comorbid epilepsy and migraine and to evaluate the maintenance of [perampanel]effectiveness in a prolonged follow-up."

An analysis of patients taking topiramate, valproate, or lamigotrine as concomitant ASMs (n = 12) compared to those not (n = 15) revealed no significant time-condition interaction of perampanel on migraine attacks (F[2,24] = 0.643; P = .534). There was a significant main effect of time, showing a decrease in migraine attacks from baseline to 6 months and from baseline to 12-month follow-up for both groups (F[2,24] = 29.528; P <.001).

In addition to a significantly different monthly mean rate usage of rescue migraine medications over the course of the study (X2[2] = 48.892; P <.001), perampanel-treated patients had median monthly use of these medications decrease from baseline (median, 2.96) to 6 months (median, 1.54; d = 0.59) and from baseline to 12-month follow-up (median, 1.50; d = 0.57).

The change in Delta scores from baseline to follow-up for both epileptic seizures and migraine attacks were positively correlated with ∆ change scores for rescue migraine medication usage. There was also a positive correlation between the ∆ change score for migraine attacks and the mean perampanel dose at 12 months. Patients who previously failed more ASMs were also positively correlated with the mean perampanel dose during that time.

Liguori and colleagues did not find a correlation between ∆ change scores for epileptic seizures and the ∆ change scores for migraine attacks; however, there was a negative correlation observed between the ∆ change score for migraine attacks and the number of concomitant ASMs.

Initially perampanel was approved in 2012 as an adjunctive therapy for partial-onset seizures (POS), and the indication was later expanded to include patients 12 years of age and older with primary generalized tonic-clonic seizures. In 2017, perampanel received a monotherapy indication for POS with or without secondary generalized seizures in those with epilepsy 12 years of age and older. The FDA then expanded the indication of perampanel for monotherapy and adjunctive use in pediatric patients 4 years of age and older for the treatment of POS with or without SGS in September 2018. Notably, the approval included both tablet and oral suspension formulations.⁴

REFERENCES
1. Fernandes M, Dono F, Dainese F, et al. Perampanel may represent an effective treatment for the prevention of migraine comorbid with epilepsy. Epilepsy Behav. Published online November 4, 2021. doi:10.1016/j.yebeh.2021.108391
2. Gameleira Ft, AtaídeJr L, Falcão Raposo CM. Relations between epileptic seizures and headaches. Seizure. 2013;22(8):622-626. doi:10.1016/j.seizure.2013.04.016
3. Romoli M, Costa C, Siliquini S, et al. Antiepileptic drugs in migraine and epilepsy: Who is at increased risk of adverse events? Cephalagia. 2018;38(2):274-282. doi:10.1177/0333102416683925
4. Eisai Announces FDA Approval of FYCOMPA in Pediatric Patients as Young as 4 Years Old for the Treatment of Partial-Onset Seizures. News release. Eisai Inc. September 28, 2018. Accessed December 1, 2021. https://www.prnewswire.com/news-releases/eisai-announces-fda-approval-of-fycompa-in-pediatric-patients-as-young-as-4-years-old-for-the-treatment-of-partial-onset-seizures-300721117.html.