Adjunctive perampanel did not worsen daytime sleepiness over ≤12 months, and in a small subset of patients, seizure frequency was reduced regardless of ESS changes, while mean QoL at end of treatment was improved for those without excessive daytime sleepiness but declined for those with excessive daytime sleepiness.
Key Findings
Results
Adjunctive perampanel did not worsen overall daytime sleepiness over up to 12 months of treatment.
Full Analysis Set (FAS) included 202 people with epilepsy (PWE) aged ≥18 years who received ≥1 perampanel dose with baseline Epworth Sleepiness Scale (ESS) scores.
Mean (SD) ESS was 6.3 (4.5) at baseline (N=202) and 6.2 (4.4) at end of treatment (EoT; n=177), indicating no meaningful change.
Excessive daytime sleepiness was defined as ESS ≥11 points.
29 PWE reported ≥4-point decreases from baseline ESS at EoT, while 31 reported ≥4-point increases, suggesting individual variability around a stable group mean.
Results
Seizure frequency was substantially reduced in both PWE with improved and worsened daytime sleepiness.
Median percent reductions in seizure frequency per 28 days from baseline were 85.6% in the improved ESS group and 77.6% in the worsened ESS group.
Both subgroups had n=14 each for this comparison.
This finding indicates that seizure reduction occurred regardless of changes in daytime sleepiness.
Results
Quality of life (QoL) at end of treatment improved for PWE without excessive daytime sleepiness but declined for those with excessive daytime sleepiness.
QoL was assessed using the QOLIE-31-P instrument.
At EoT, 14 PWE with no excessive daytime sleepiness reported a mean (SD) QOLIE-31-P score change of +7.9 (12.9) points.
11 PWE with excessive daytime sleepiness had a mean (SD) QOLIE-31-P score change of -3.4 (18.6) points.
These analyses were conducted in a small subset of patients, limiting generalizability.
Results
The overall incidence of treatment-emergent adverse events was 56.9%, with dizziness/vertigo and somnolence being the most common.
Overall incidence of treatment-emergent adverse events (TEAEs) was 56.9% across the FAS (N=202).
The most commonly reported TEAEs were dizziness/vertigo (22.8%) and somnolence (8.4%).
No new safety signals emerged beyond those already known for perampanel.
Somnolence incidence of 8.4% is consistent with the known perampanel safety profile.
Methods
The study population consisted of adults with insufficiently controlled focal-onset seizures prescribed adjunctive perampanel in a prospective, observational Italian study.
AMPA (NCT04257604) was a prospective, observational study conducted in Italy.
PWE were aged ≥12 years with insufficiently controlled focal-onset seizures, with or without focal to bilateral tonic-clonic seizures, on 1–3 baseline anti-seizure medications.
The FAS for this post hoc analysis included PWE ≥18 years who received ≥1 perampanel dose and had baseline ESS scores (N=202).
ESS was administered at baseline and each study visit for ≤12 months.
What This Means
This research examined whether adding the seizure medication perampanel to existing treatment affected daytime sleepiness and quality of life in adults with epilepsy whose seizures were not well controlled. Using data from a real-world observational study conducted in Italy, researchers tracked 202 adults over up to 12 months using the Epworth Sleepiness Scale (ESS), a standard questionnaire measuring daytime drowsiness, and a quality-of-life tool specific to epilepsy (QOLIE-31-P). The study found that, on average, perampanel did not make daytime sleepiness worse — the group-level ESS scores were nearly identical at the start and end of the study. However, there was individual variability, with some patients reporting improved sleepiness and others reporting worsened sleepiness.
The research also found that seizure frequency dropped substantially in both patients whose sleepiness improved and those whose sleepiness worsened, suggesting that perampanel's anti-seizure benefit occurred regardless of its effect on sleepiness. Quality of life improved slightly for patients who did not have excessive daytime sleepiness at the end of treatment, while it declined modestly in those who did experience excessive daytime sleepiness. These QoL findings were based on small subgroups (14 and 11 patients, respectively), so they should be interpreted cautiously.
This research suggests that perampanel may be a viable add-on treatment option for people with difficult-to-control focal seizures without broadly worsening daytime sleepiness, though individual responses vary. The most common side effects were dizziness/vertigo (in about 23% of patients) and somnolence (in about 8%), consistent with what is already known about this medication. The findings highlight that managing daytime sleepiness in epilepsy patients may be important for maintaining or improving their overall quality of life during treatment.
Liguori C, Assenza G, Chiacchiaretta M, Patten A, Sáinz-Fuertes R, Gentile A. (2026). Effect of adjunctive perampanel on daytime sleepiness and quality of life in adults with focal-onset seizures: Post hoc analyses of the AMPA study.. Epilepsy & behavior : E&B. https://doi.org/10.1016/j.yebeh.2026.110962