A review on orexin receptor antagonists in chronic insomnia: a revolutionary approach

Chronic insomnia is a chronic sleep disorder characterized by the inability to fall asleep or stay asleep. Other than hyperarousal, altered circadian rhythms, and behavioral changes, it can also occur due to medical or psychiatric conditions. The use of benzodiazepines, Z-drugs, melatonin agonists, antihistamines, and sedative antidepressants as traditional treatment in chronic insomnia offer relief, but are also coupled with several limitations like tolerance, dependence, residual sedation, and disruption of normal sleep architecture. With the continuous revealing of the sleep neurobiology mystery, the orexin system has been pinpointed as a main regulator of wakefulness and arousal, thus making it a probable therapeutic target. Orexin receptor antagonists like suvorexant, lemborexant, and daridorexant inhibit the selective OX1R and OX2R pathways thereby decreasing the wakefulness and facilitating natural, continuous sleep. These medications have shown to enhance sleep by reducing the time to fall asleep, the number of times one wakes up and thereby increasing the total time spent during sleep, without impairing the normal sleep architecture. They are regarded as a breakthrough and more natural means of treating chronic insomnia because of their good safety profile and the low risk of next-day sedation they come with.