lemborexant

General Information

Lemborexant 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).

Lemborexant is contraindicated in narcolepsy and is a Schedule IV controlled substance; clinicians often screen for misuse risk and limit open-ended refills.

The lemborexant compare view, the lemborexant evidence feed, and the lemborexant print page support side-by-side review when weighing orexin-based options against sedative-hypnotics.

Contraindicated in narcolepsy; commonly used as a time-limited adjunct alongside CBT-I and sleep hygiene with attention to daytime impairment and polypharmacy risks. Short prescriptions and a documented stop plan are common; longer-term continuation typically depends on meaningful benefit after a reasonable trial.

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 also produce “REM intrusion” symptoms (sleep paralysis, 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

• Metabolized primarily by CYP3A (label).
• Effective half-life is ~17–19 hours (label).
• Time to effect may be delayed if taken with or soon after a meal (label).
• Longer effective half-life can increase next-day impairment, especially at higher doses, in older adults, and with polypharmacy; conservative dosing and reassessment of driving and falls risk are common.

Dosing and Administration

• Typical starting dose is 5 mg once nightly immediately before bedtime, with at least 7 hours remaining before planned awakening; maximum 10 mg nightly (label).
• Strong/moderate CYP3A inhibitors and strong/moderate CYP3A inducers are generally avoided; with weak CYP3A inhibitors, the maximum recommended dose is 5 mg (label).
• “Middle of the night” redosing increases next-day impairment risk and is generally avoided; persistent awakenings often prompt reassessment of the diagnosis and consideration of alternatives rather than increasing hypnotic burden.

Monitoring & Labs

• Next-day impairment (driving, work, falls) is assessed after initiation and dose changes; dose reduction or discontinuation may be considered when safety is compromised.
• REM intrusion symptoms (sleep paralysis, hallucinations) are screened for; discontinuation may be considered if they are distressing or dangerous.
• Interacting medications (CYP3A modulators) are reviewed, and alcohol or other CNS depressants are minimized when possible.
• Benefit is reassessed at each refill decision; ongoing use typically depends on meaningful improvement after an adequate trial.

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

Adverse Effects

Interactions

• CYP3A inhibitors increase exposure; CYP3A inducers reduce exposure (label).
• Additive sedation with alcohol and other CNS depressants.
• When CYP3A modulators are started or stopped, reassess next-day impairment and driving risk is often reassessed, and switching agents may be considered rather than overriding interaction precautions.
• Combining with other sedative-hypnotics increases impairment; minimizing combinations is preferred when feasible. When combinations occur, lower starting doses and closer follow-up are common to reduce falls and driving risk.

Other Useful Information

• CBT-I is typically first-line, with lemborexant used as a time-limited adjunct with ongoing reassessment.
• Contraindicated in narcolepsy; older adults and serious mental illness with polypharmacy often warrant added caution.
• If insomnia persists, assessment often includes untreated sleep apnea, circadian rhythm disorders, stimulant use, alcohol/cannabis use, and mood episodes before adding additional sedatives.
• Short prescriptions with planned follow-up are common; discontinuation is typically recommended if REM intrusion symptoms, next-day impairment, or unsafe nighttime behaviors occur.

References

1. Dayvigo (lemborexant) prescribing information — DailyMed (2025)
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)