To identify which anti-seizure medications (ASMs) are associated with excessive daytime sleepiness and determine management strategies when it occurs.

Daytime sleepiness is known to occur with epilepsy itself and is often exacerbated by ASMs. There is limited information available to clinicians on the extent of daytime sleepiness induced by ASMs and how it should be managed, especially with newer ASMs.

We conducted a retrospective chart review of adult patients with epilepsy who visited our neurology department between January and October 2024.

Among 207 adult patients with epilepsy (37.7% female, mean age: 46.6 years), adverse events due to ASMs were observed in 58 (28.0%). Of these, 26 patients (12.6%) experienced excessive daytime sleepiness necessitating dose reduction or discontinuation of ASMs. There was no age-related difference in the incidence of excessive daytime sleepiness. Clonazepam: 33.3% (3 of 9), Levetiracetam: 20.9% (19 of 91), Zonisamide: 7.1% (1 of 14), and Valproate: 3.8% (1 of 30) were associated with higher incidences of excessive daytime sleepiness. There was a relatively high incidence of drug eruptions (13.0% / 6 of 46) with Lamotrigine, although daytime sleepiness was not observed. No patients developed excessive daytime sleepiness with Lacosamide and Perampanel. When excessive daytime sleepiness occurred, switching to Lacosamide (27.0% / 7 of 26) and Perampanel (11.5% / 3 of 26), along with dose reduction of the causative ASMs, improved daytime sleepiness.

Among newer ASMs, there are differences in their tendency to cause excessive daytime sleepiness, with Clonazepam and Levetiracetam being more commonly associated with this side effect, thus warranting caution. Conversely, Perampanel and Lacosamide are less likely to cause daytime sleepiness, and ASM selection should be tailored to the sleep characteristics of epileptic patients.