Sleep effects in drug-resistant epileptic patients taking perampanel: an observational study.
Lamanna F, Pardeo O, et al. • Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology • 2026
Perampanel appears to preserve sleep quality and mildly improve quality of life, and shows greater efficacy when used as a first add-on therapy in drug-resistant epilepsy.
Key Findings
Results
Perampanel showed greater seizure reduction efficacy when used as a first add-on therapy compared to late add-on therapy in drug-resistant epilepsy patients.
In the first add-on group (n=11), 100% of patients were responders (≥50% seizure reduction) and 27.2% were seizure-free.
In the late add-on group (n=20), 65% were responders and 30% were seizure-free.
The difference in responder rates between groups was statistically significant (p=0.043).
Patients were followed for six months at the Epilepsy Center of the University of Messina, Italy.
Results
Sleep quality and daytime sleepiness showed slight improvement following perampanel treatment.
Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) at baseline and follow-up.
Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS) at baseline and follow-up.
Improvements in both PSQI and ESS were described as 'slight', suggesting perampanel preserves rather than substantially improves sleep.
The study included 31 patients total, with one excluded due to seizure worsening, leaving 30 evaluable patients.
Results
Quality of life showed a mild, non-significant overall improvement, but seizure worry was significantly reduced in late add-on patients.
Quality of life was assessed using the QOLIE-31 (Quality of Life in Epilepsy-31) instrument at baseline and follow-up.
The overall improvement in QOLIE-31 scores was described as 'mild' and 'non-significant'.
A significant reduction in seizure worry was specifically observed in the late add-on patient group.
No specific p-values for QOLIE-31 overall scores or PSQI/ESS changes were reported in the abstract.
Results
Perampanel was well tolerated with no severe adverse events reported over six months of follow-up.
Tolerability was assessed through reported adverse events throughout the observation period.
No severe adverse events were recorded in either the first add-on or late add-on groups.
PER was used as add-on therapy in all patients, consistent with its approved indication.
Only one patient was excluded from analysis, due to seizure worsening rather than an adverse event.
Methods
The study enrolled 31 drug-resistant epilepsy patients receiving perampanel as add-on therapy, stratified into first add-on (n=11) and late add-on (n=20) groups.
Patients were recruited at the Epilepsy Center of the University of Messina, Italy according to ILAE criteria for drug-resistant epilepsy.
Perampanel is a selective non-competitive antagonist of the AMPA receptor.
Efficacy was classified as worsened, unchanged, <50% improvement, ≥50% improvement, or seizure-free based on seizure frequency reduction.
The observational study design involved assessments at baseline and at six-month follow-up.
What This Means
This research studied how perampanel, an anti-seizure medication that works by blocking a specific brain receptor (AMPA), affects sleep and quality of life in people with epilepsy that has not responded to other treatments. Thirty-one patients were followed for six months at an epilepsy center in Italy, and researchers measured their sleep quality, daytime sleepiness, and overall quality of life before and after starting perampanel as an add-on to their existing medications.
The study found that perampanel generally preserved sleep quality and caused slight improvements in both sleep and daytime sleepiness, which is notable because some anti-seizure medications can disrupt sleep. Quality of life showed mild improvement overall, though this was not statistically significant. However, patients who worried most about seizures — those in the group for whom perampanel was a later addition to their treatment — showed a significant reduction in seizure-related worry. Importantly, the medication worked better when it was added earlier in the treatment process: patients receiving it as their first add-on medication had a 100% response rate (meaning all of them experienced at least a 50% reduction in seizures), compared to 65% in patients who had already tried multiple other add-on medications. No serious side effects were reported in either group.
This research suggests that perampanel may be a well-tolerated option for people with difficult-to-treat epilepsy, and that using it earlier in the treatment sequence — before trying many other add-on medications — may lead to better seizure control. The findings also suggest that perampanel does not negatively affect sleep, which is an important consideration given that sleep disruption is common in epilepsy and can worsen seizure frequency. However, the study was small (31 patients) and observational in design, so larger controlled studies would be needed to confirm these findings.
Lamanna F, Pardeo O, Tilenni D, Luppino F, Salafica G, Barbaccia A, et al.. (2026). Sleep effects in drug-resistant epileptic patients taking perampanel: an observational study.. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. https://doi.org/10.1007/s10072-025-08785-5