daridorexant

General Information

Daridorexant is a dual orexin receptor antagonist (DORA) approved for insomnia (sleep onset and sleep maintenance).

DORAs target orexin-mediated wake drive and do not rely on GABA-A modulation; this can be useful when avoiding GABAergic hypnotics, but next-day impairment and additive sedation risks still apply.

Key safety issues are next-day impairment, additive sedation with other CNS depressants, and uncommon “REM intrusion” symptoms (sleep paralysis, hypnagogic hallucinations) (label).

Daridorexant is contraindicated in narcolepsy and is a Schedule IV controlled substance; misuse risk is commonly assessed and refills are typically time-limited.

The daridorexant compare view, daridorexant evidence feed, and daridorexant print page can support shared decision-making when weighing orexin-based options against sedative-hypnotics.

Contraindicated in narcolepsy; often used as a time-limited adjunct alongside CBT-I and sleep hygiene, with monitoring for daytime impairment and polypharmacy risks. Prescriptions are typically short with planned follow-up; if benefit is minimal after a reasonable trial, discontinuation is often considered rather than indefinite continuation.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Antagonist of orexin OX1R and OX2R receptors, reducing wake drive and facilitating sleep.

Orexin antagonism can produce “REM intrusion” symptoms such as sleep paralysis and hypnagogic hallucinations (label).

Orexin signaling supports wakefulness; blocking it can help sleep onset and maintenance, but clinical response varies and should be paired with behavioral sleep strategies.

• Dual orexin receptor antagonism (OX1R/OX2R).

Metabolism and Pharmacokinetics

• Daridorexant is primarily metabolized by CYP3A4 (label).
• Terminal half-life is ~8 hours (label).
• Primarily excreted as metabolites via feces and urine (label).

Dosing and Administration

• Typical dose range is 25–50 mg once nightly within 30 minutes of bedtime, with at least 7 hours remaining before planned awakening (label).
• Label recommends avoiding strong CYP3A4 inhibitors; with moderate CYP3A4 inhibitors, label limits dosing to 25 mg (maximum 25 mg) (label).
• Coadministration with strong or moderate CYP3A4 inducers can reduce effect and is generally avoided (label).
• “Middle of the night” redosing is generally discouraged; persistent awakenings often prompt reassessment of diagnosis and alternatives rather than increasing hypnotic burden.

Monitoring & Labs

• Next-day impairment (driving, work, falls) after initiation and dose changes; if safety is compromised, dose reduction or discontinuation is commonly considered.
• REM intrusion symptoms (sleep paralysis, hallucinations); distressing or dangerous symptoms usually prompt discontinuation.
• Review interacting medications (CYP3A modulators); alcohol and other CNS depressants are generally avoided.
• Benefit at each refill decision; discontinuation is considered if insomnia does not improve after an adequate trial.

Sources: FDA/DailyMed label; AASM insomnia guideline; evidence reviews.

Adverse Effects

Interactions

• CYP3A4 inhibitors increase exposure; CYP3A4 inducers reduce exposure (label).
• Additive sedation with alcohol and other CNS depressants.
• Combining with other sedative-hypnotics increases impairment risk and is generally avoided; if combinations are unavoidable, lower dosing and closer follow-up are commonly used to reduce falls and driving risk.

Other Useful Information

• CBT-I is typically first-line; daridorexant is often used as a time-limited adjunct with ongoing reassessment (e.g., a simple sleep metric) and a documented review/stop plan.
• Contraindicated in narcolepsy; caution is warranted in older adults and in serious mental illness with polypharmacy.
• If insomnia persists, evaluation for untreated sleep apnea, circadian rhythm disorders, stimulant use, alcohol/cannabis use, and mood episodes is important before layering additional sedatives.
• Prescriptions are often time-limited with planned follow-up; REM intrusion symptoms, next-day impairment, or unsafe nighttime behaviors generally prompt reassessment and discontinuation when appropriate.

References

1. Quviviq (daridorexant) prescribing information — DailyMed (2024)
2. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline — Journal of Clinical Sleep Medicine (2017)
3. Efficacy and Acceptability of Pharmacological Interventions for Insomnia in Patients With Severe Mental Illness — Acta Psychiatrica Scandinavica (2025)
4. Residual effects of medications for sleep disorders on driving performance — European Neuropsychopharmacology (2024)