Daridorexant, sold under the brand name Quviviq, is an orexin antagonist medication which is used for the treatment of insomnia. Daridorexant is taken by mouth.

Side effects of daridorexant include headache, somnolence, and fatigue. The medication is a dual orexin receptor antagonist (DORA). It acts as a selective dual antagonist of the orexin receptors OX₁ and OX₂. Compared to other marketed OX antagonists, daridorexant has a relatively short elimination half-life of 8 hours and a time to peak of about 1 to 2 hours. It is not a benzodiazepine or Z-drug and does not interact with GABA receptors, instead having a distinct mechanism of action.

Daridorexant was approved for medical use in the United States in January 2022 and became available in May 2022. It was approved in the European Union in April 2022, and is the first orexin receptor antagonist to become available in European Union. The medication is a schedule IV controlled substance in the United States and may have a modest potential for misuse. Besides daridorexant, other orexin receptor antagonists, like suvorexant and lemborexant, have also been introduced.

Daridorexant is indicated for the treatment of adults with insomnia characterized by difficulties with sleep onset and/or sleep maintenance. The medication has been found to significantly improve latency to persistent sleep (LPS), wake after sleep onset (WASO), and subjective total sleep time (TST) in regulatory clinical trials. At doses of 25 to 50 mg and in terms of treatment–placebo difference, it reduces LPS by 6 to 12 minutes, reduces WASO by 10 to 23 minutes, and increases subjective TST by 10 to 22 minutes. Daridorexant has also been found to improve daytime functioning at a dose of 50 mg but not at 25 mg.

Network meta-analyses have assessed the sleep-promoting effects of orexin receptor antagonists and have compared them between one another as well as to other sleep aids including benzodiazepines, Z-drugs, antihistamines, sedative antidepressants (e.g., trazodone, doxepin, amitriptyline, mirtazapine), and melatonin receptor agonists. A major systematic review and network meta-analysis of insomnia medications published in 2022 found that daridorexant had an effect size (standardized mean difference (SMD)) against placebo for treatment of insomnia at 4 weeks of 0.23 (95% CITooltip confidence interval –0.01 to 0.48). This was similar to but numerically lower than the effect sizes at 4 weeks for suvorexant (SMD 0.31, 95% CI 0.01 to 0.62) and lemborexant (SMD 0.36, 95% CI 0.08 to 0.63). Benzodiazepines and Z-drugs generally showed larger effect sizes than orexin receptor antagonists (e.g., SMDs of 0.45 to 0.83). The review concluded on the basis of daridorexant's small effect size that it did not show an overall material benefit in the treatment of insomnia. Conversely, it concluded that lemborexant—as well as the Z-drug eszopiclone—had the best profiles overall in terms of efficacy, tolerability, and acceptability among all of the assessed insomnia medications.

Orexin receptor antagonists are not used as first-line treatments for insomnia due to their costs and concerns about possible misuse liability.

Population pharmacokinetic modeling indicates that differences between subjects do not require dose adjustments, and that lean body weight and fat mass effect the pharmacokinetics of daridorexant better than other body size descriptors.

Treatment with daridorexant is generally safe and well tolerated for up to one year, with improvements in sleep and daytime functioning persisting throughout treatment.