Daridorexant, an Orexin Receptor Antagonist for the Management of Insomnia

Background:Insomnia is a common sleep disorder that is diagnosed primarily by patients' subjective reported symptoms. Daridorexant is a new dual orexin receptor antagonist that was recently approved by Food and Drug Administration for insomnia characterized by difficulty falling asleep and/or maintaining sleep.Mechanism of Action, Pharmacodynamics, and Pharmacokinetics:The orexin neuropeptide signaling system plays a role in wakefulness, and blocking the wake-promoting neuropeptides results in diminished wake signaling, thus exerting a sedative effect using an entirely different mechanism of action than the classical sleep promoting agents. The drug has quick onset of action, high volume of distribution, and high protein binding. Pharmacokinetics and pharmacodynamic parameters were similar in patients of different sex and age and were not significantly affected by race, body size, or mild-to-moderate kidney impairment. Dose limitation to 25 mg in moderate liver impairment and no use in severe liver impairment are recommended. The drug undergoes hepatic CYP3A4 metabolism; thus, caution with strong CYP3A4 inhibitors and inducers is warranted.Therapeutic Advance:Daridorexant is a novel agent with demonstrated efficacy in sleep onset and maintenance and decrease in daytime sedation. Preliminary results from a 1-year extension study note similar incidences of mild-to-moderate side effects as noted in previous trials. Further studies are needed to establish its place in the pharmacological treatment of insomnia.