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 shiftwork disorder. This review highlights the pressing need to improve patient access to evidencebased treatments in South Korea and to generate domestic real-world data to support clinical decision-making and health policy revision.
J Korean Neurol Assoc 43(4):233-244, 2025