Excessive daytime sleepiness (EDS) is a prevalent symptom that significantly impairs quality of
life and poses substantial public health risks. A precise differential diagnosis is crucial, beginning
with common causes such as insufficient sleep, circadian rhythm sleep-wake disorders, and
sleep-disrupting conditions like obstructive sleep apnea (OSA), before proceeding to the
central disorders of hypersomnolence. This review provides a comprehensive overview of
pharmacological agents for the treatment of EDS, including modafinil/armodafinil, pitolisant,
solriamfetol, sodium oxybate, methylphenidate, and amphetamines. We provide a comparative
analysis of clinical practice guidelines and regulatory status in the United States, Europe,
and Japan, highlighting differences in first-line recommendations, approved indications, and
therapeutic algorithms for conditions such as narcolepsy, idiopathic hypersomnia, residual EDS
in OSA, and shift-work sleep disorder. Furthermore, we address the unique clinical landscape in
South Korea, where significant discrepancies exist between drug approvals and reimbursement
criteria. Limited health insurance coverage, the unavailability of key medications such as
solriamfetol and sodium oxybate, and the recent withdrawal of pitolisant from the market severely restrict therapeutic options. These challenges create a substantial unmet need,
particularly for pediatric patients and those with OSA-related residual sleepiness or shift
work disorder. This review highlights the pressing need to improve patient access to evidence
based treatments in South Korea and to generate domestic real-world data to support clinical
decision-making and health policy revision.