Daridorexant

Dual orexin receptor antagonist (DORA)

Daridorexant

Quviviq

Daridorexant (brand name Quviviq) is a dual orexin receptor antagonist (DORA) FDA-approved in January 2022 for insomnia. Among the three approved DORAs, daridorexant has the shortest half-life (~8 hours vs lemborexant ~17-19 h and suvorexant ~12 h), which may reduce next-day residual sedation. Mechanism: orexin/hypocretin neurons in the lateral hypothalamus drive arousal; blocking both OX1R and OX2R reduces wake-promoting signaling. The result is sleep that resembles normal physiologic sleep more closely than GABAergic hypnotics (less REM suppression, fewer abnormal sleep behaviors). DORAs may be particularly useful when sleep maintenance (rather than just sleep onset) is the problem, since they reduce arousal across the night without enhancing GABA-mediated inhibition.

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Titration strategies

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Effects

Headache, somnolence (next-day), fatigue, dizziness, nausea. Sleep paralysis, hallucinations near sleep onset reported. Complex sleep behaviors (sleep-driving, etc.), class warning. Lower next-day impairment than benzos/Z-medicines in trials.

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Pharmacodynamics

Selective dual antagonist at OX1R (Ki ~0.5 nM) and OX2R (Ki ~0.9 nM). No significant binding at other receptors. Minimal effect on REM/NREM sleep architecture.

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Summary

Classes

Dual orexin receptor antagonist (DORA)

Pharmacy

Starting dose

25 mg PO at bedtime (no titration); may increase to 50 mg if 25 mg inadequate

Preparations

25 mg, 50 mg tablets

US FDA Max

50 mg/d

Pharmacology

Routes

Oral

Onset

~30 min

Duration

~7-8 hours

Half-life

~8 hours (shorter than suvorexant and lemborexant)

Bioavailability

~62%

Pregnancy

Limited data; avoid

Legal status

Rx, Schedule IV (US)

Purported mechanism

Selective antagonist at both orexin (OX1R, OX2R) receptors. Orexin/hypocretin from lateral hypothalamus is a key wake-promoting neuropeptide; antagonizing its receptors reduces arousal and promotes sleep. Unlike GABAergic hypnotics (benzos, Z-medicines), DORAs do not enhance inhibitory tone, they reduce excitatory tone. Less effect on sleep architecture and possibly lower next-day impairment.