Rationale:
Perampanel is a selective AMPA receptor antagonist approved for focal and generalized seizures. However, data identifying patient subgroups that particularly benefit or are adversely affected by perampanel remain limited. This study aimed to investigate the real-world effectiveness and safety of perampanel and identify patient characteristics associated with treatment outcomes.
Methods:
This retrospective observational study included adults (≥19 years) with epilepsy who initiated perampanel between December 2018 and May 2025 at Asan Medical Center, Korea. Among 159 screened patients, 117 were analyzed after excluding those with early follow-up loss, missing baseline data, or early adjustment of concurrent ASMs. Perampanel was initiated at 2 mg/day and titrated after one month. Effectiveness was assessed by 50% responder rates and seizure freedom (no seizures in the prior 3 months) at 3, 6, 12, and 24 months, censoring upon increase or addition of other ASMs. Retention and adverse events (AEs) were evaluated for all patients using chi-square and Fisher’s exact tests.
Results:
Among the 117 patients, retention rates at 3, 6, 12, and 24 months were 96.6%, 90.6%, 80.3%, and 68.4%, respectively. Responder rates were 59.8%, 57.9%, 62.2%, and 56.8%, and seizure freedom rates were 40.2%, 40.4%, 38.8%, and 46.9% at each time point (Figure 1). Age ≥50 was associated with higher responder rates at 12 months (p = 0.009). Frontal lobe epilepsy predicted better seizure freedom at 12 months (p = 0.039), while enzyme-inducing ASMs were linked to lower seizure freedom at 12 months (p = 0.025). Levetiracetam co-treatment was associated with improved retention at 24 months (p=0.044).
AEs occurred in 74 patients (63.2%), leading to discontinuation in 22 (29.7%). Dose reductions were performed in 33 patients (44.6%), with symptom improvement in 27 (81.8%). Common AEs included dizziness (33.3%), aggression (9.4%), depression (6.8%), and ataxia (6.8%) (Figure 2). Psychiatric comorbidities strongly predicted psychiatric AEs (p = 0.015). Three serious AEs occurred, all suicide attempts in patients with pre-existing depression. Patients with post-traumatic epilepsy had higher rates of ataxia (p = 0.027) and psychiatric AEs (p = 0.032). Lamotrigine co-use (p = 0.022) and frontal lobe lesions (p = 0.042) were associated with fewer overall AEs.
Conclusions:
Perampanel showed favorable long-term effectiveness and tolerability in this real-world Korean study. Patients with psychiatric comorbidities or using enzyme-inducing ASMs may have a higher risk of AEs and suboptimal outcomes, suggesting cautious use or avoidance of perampanel in these groups. In contrast, perampanel appears well-tolerated when added to lamotrigine or levetiracetam. Patients with frontal lobe lesions may particularly benefit from perampanel use.
Funding:
This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: RS-2023-KH139976).