Real-World Study Shows Stable Daytime Sleepiness With Adjunctive Perampanel in Epilepsy

Adjunctive treatment with perampanel does not worsen daytime sleepiness in patients with focal-onset seizures (FOS) over a 12-month treatment period, according to a post hoc analysis of the real-world AMPA study (NCT04257604). Investigators also observed substantial reductions in seizure frequency across patient subgroups, suggesting seizure control with perampanel can be achieved without negatively affecting daytime alertness.

The analysis included 202 adults with epilepsy who had baseline Epworth Sleepiness Scale (ESS) scores and received at least one dose of perampanel. ESS scores remained largely unchanged throughout the study, with a mean score of 6.3 (SD, 4.5) at baseline and 6.2 (SD, 4.4) at end of treatment among the 177 participants with available follow-up data.

Daytime Sleepiness Remained Stable During Treatment

The Epworth Sleepiness Scale is a patient-reported questionnaire that evaluates daytime sleep propensity across common daily scenarios, such as watching television or resting in the afternoon. In the AMPA analysis, the median ESS score was 5 at baseline and remained unchanged at the end of treatment, with a median change of 0 points over the 12-month study period.

Although overall ESS scores were stable, some patients experienced clinically meaningful changes in daytime sleepiness. Sixty participants had a change of at least 4 points in ESS score, which investigators defined as clinically relevant. Of these, 29 reported improvement in daytime sleepiness and 31 reported worsening.

Perampanel dosing was broadly similar between these groups. Patients with improved daytime sleepiness had a mean final perampanel dose of 6.8 mg/day, while those whose sleepiness worsened had a mean dose of 5.8 mg/day. Many participants in both groups were also receiving anti-seizure medications known to affect sleep quality, including benzodiazepines, lamotrigine, oxcarbazepine, phenobarbital, and valproic acid.

Study authors, which included Claudio Liguori, MD, PhD, medical doctor at the University of Rome, noted that these findings suggest perampanel itself may not meaningfully influence daytime sleep propensity even when used alongside other medications associated with sleep-related adverse effects. As the authors wrote, “incorporation of perampanel in the existing ASM treatment regimen may not affect daytime sleep propensity in individuals with treatment-resistant focal-onset seizures.”

Seizure Control Observed Across Sleepiness Subgroups

Among a subset of 28 patients with available seizure frequency data, seizure reductions were observed regardless of whether daytime sleepiness improved or worsened during treatment. Overall, patients who experienced improvement in daytime sleepiness showed a median reduction in seizure frequency of 85.6% per 28 days from baseline. Those whose daytime sleepiness worsened still experienced substantial seizure reductions, with a median reduction of 77.6%.

Although the small subgroup size limited statistical comparisons, investigators reported consistent patterns linking greater seizure reduction with lower daytime sleep propensity. Liguori et al concluded that these findings aligned with prior research suggesting improved seizure control may positively influence sleep quality and daytime alertness.

Changes in Excessive Daytime Sleepiness and Quality of Life

At baseline, 28 participants—representing 13.9% of the study population—met the definition of excessive daytime sleepiness, defined as an ESS score of at least 11. By the end of treatment, 17 of these patients (60.7%) had ESS scores below this threshold, suggesting improvement in daytime alertness during the study period.

Quality-of-life outcomes appeared to differ based on changes in daytime sleepiness. Among patients with excessive daytime sleepiness at baseline, those whose ESS scores normalized showed a mean increase of 7.9 points on the QOLIE-31-P quality-of-life scale. In contrast, patients whose daytime sleepiness persisted experienced a mean decrease of 3.4 points.

Because a 5.2-point change in QOLIE-31-P is generally considered clinically meaningful, the improvement observed among patients whose daytime sleepiness resolved may represent a meaningful quality-of-life benefit. Investigators suggested that improved seizure control may have contributed to these changes, noting that reduced seizure burden can allow patients to participate more freely in daily activities.

Safety Findings Consistent With Previous Studies

Safety outcomes from the AMPA study were consistent with the known safety profile of perampanel. Overall, 56.9% of participants reported at least one treatment-emergent adverse event, and no new safety signals were identified.

The most frequently reported events were dizziness or vertigo, occurring in 22.8% of participants, followed by somnolence in 8.4%. Investigators noted that most patients who reported somnolence did not experience clinically meaningful changes in ESS scores during the study period, suggesting that reports of somnolence did not necessarily correspond to sustained increases in daytime sleepiness.

Clinical Implications

Excessive daytime sleepiness is a common comorbidity in epilepsy and can arise from multiple factors, including seizure activity, sleep disruption, and medication effects. Understanding the impact of anti-seizure therapies on daytime alertness is therefore an important aspect of treatment selection.

Although the analysis was limited by its post hoc design, reliance on subjective sleepiness measures, and relatively small subgroup sizes, the findings suggest that adjunctive perampanel does not appear to worsen daytime sleepiness in patients with focal epilepsy. At the same time, the therapy was associated with substantial seizure reduction and a safety profile consistent with prior studies.

Overall, the authors concluded that perampanel may help improve seizure control without compromising daytime alertness, while exploratory findings also suggest potential benefits in quality of life for some patients.

REFERENCE
1. Liguori C, Assenza G, Chiacchiaretta M, Patten A, Sainz-Fuertes R, Gentile AL. 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 & Behav. 2026;178:110962. doi: