Perspectives on idiopathic hypersomnia: diagnostic challenges, unknown pathophysiological, and emerging therapeutic strategies

Idiopathic hypersomnia (IH) is a rare chronic neurological condition that may be characterized by excessive daytime sleepiness (EDS), and/or prolonged nocturnal sleep, and also sleep inertia, yet its underlying mechanisms and diagnostic boundaries remain poorly defined. A key challenge is distinguishing excessive sleep duration from EDS, as patients may present one or both features, and similar symptoms can arise from diverse medical, psychiatric, and sleep disorders. Current diagnostic criteria rely heavily on the multiple sleep latency test, which frequently underestimates hypersomnia in patients with long sleep need, demonstrates poor test-retest reliability, and separates IH from narcolepsy type 2 based on an unstable count of sleep-onset REM periods. Accurate measurement of long sleep is an unmet need. Actigraphy and sleep diaries frequently misestimate true sleep duration, while extended polysomnography, the gold standard, is rarely feasible outside research. Defining abnormal sleep quantity remains difficult given individual variability and the heterogeneity of IH phenotype. The pathophysiology of IH remains largely speculative. No definitive biomarker has been identified, and proposed mechanisms, including genetic susceptibility, circadian alterations, abnormal slow-wave dynamics, and neurobiology disturbances lack consistent validation. Clinical overlap between IH and hypersomnolence associated with depression suggests potential shared disruptions in arousal and circadian-homeostatic systems, though their neurobiological bases remain unclear. Therapeutic approaches are still limited. Low-sodium oxybate offers symptomatic improvement, and orexin receptor agonists represent an encouraging emerging class. Advancing the field will require better phenotyping, standardized sleep extension methods, and biomarkers to define IH as a distinct multidimensional disorder rather than a diagnosis of exclusion.