Review of Dual Orexin Receptor Antagonists on Treatment of Insomnia and Beyond

Insomnia is a sleep disorder that not only causes daytime impairment but is also associated with increased health risks. Besides treatment with cognitive behavioral therapy, pharmacologic options remain limited with the potential significant adverse effects that must be carefully monitored and weighted against the benefits. The orexin system plays a crucial role in sleep-wake regulation and since the development of dual orexin receptor antagonists, increasing research studies have shown their promising effect on improving both sleep onset and sleep maintenance without significant adverse events, dependence, tolerance, or withdrawal. Recent data have found additional benefits of targeting the orexin system in treatment or dementia, delirium, mood disorders, menopause, substance use disorders, eating disorders, and obstructive sleep apnea.