Statement of Significance
sleep disorder, narcolepsy, daytime sleepiness, idiopathic hypersomnia, disorders of hypersomnolence
NARCOLEPSY, IDIOPATHIC HYPERSOMNIA, PATHOPHYSIOLOGY
The pathophysiology of idiopathic hypersomnia is poorly understood, resulting in a lack of specific treatments for the condition. Agents targeting the orexin neuropeptide system have been found to improve wakefulness in people with narcolepsy but have not been investigated in other disorders of hypersomnolence. We found that a single infusion of the orexin-2 receptor agonist danavorexton improves subjective and objective excessive daytime sleepiness in adults with idiopathic hypersomnia, suggesting that orexin-2 receptor agonists hold promise for the treatment of this disabling sleep disorder.