suvorexant

General Information

Suvorexant 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, cataplexy-like symptoms) (label).

Suvorexant is contraindicated in narcolepsy and is a Schedule IV controlled substance; screen for misuse risk and avoid open-ended refills.

The suvorexant compare view, suvorexant evidence feed, and suvorexant print page can support weighing insomnia options that do not rely on GABA-A modulation.

Contraindicated in narcolepsy; treat as a time-limited adjunct alongside CBT-I and sleep hygiene with close monitoring for daytime impairment. Use short prescriptions, define a stop plan, and stop rather than continuing indefinitely if benefit is minimal 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, cataplexy-like symptoms) (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 with minor contribution from CYP2C19 (label).
• Mean half-life is ~12 hours; primarily eliminated via feces (label).
• Time to effect may be delayed if taken with or soon after a meal (label).
• Longer half-life can increase next-day impairment, especially at higher doses, in older adults, and with polypharmacy; dose conservatively and reassess driving and falls risk.

Dosing and Administration

• Typical dose is 10 mg once nightly within 30 minutes of bedtime, with at least 7 hours remaining before planned awakening; maximum 20 mg nightly (label).
• With moderate CYP3A inhibitors, recommended dose is 5 mg (generally do not exceed 10 mg); avoid strong CYP3A inhibitors (label).
• Avoid alcohol and other sedatives when possible; reassess frequently.
• Avoid “middle of the night” redosing; if awakenings persist, reassess the diagnosis and consider alternatives rather than increasing hypnotic burden.

Monitoring & Labs

• Assess next-day impairment (driving, work, falls) after initiation and dose changes; lower the dose or stop if safety is compromised.
• Screen for REM intrusion symptoms (sleep paralysis, hallucinations, cataplexy-like symptoms) and discontinue if they are distressing or dangerous.
• Review interacting medications (CYP3A modulators) and avoid alcohol or other CNS depressants when possible.
• Reassess benefit at each refill decision and stop if insomnia does not improve after an adequate trial.

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

Adverse Effects

Interactions

• Strong CYP3A inhibitors increase exposure—avoid combination; moderate inhibitors require dose reduction (label).
• Strong CYP3A inducers can reduce effect (label).
• Additive sedation with alcohol and other CNS depressants.
• Avoid combining with other sedative-hypnotics when possible; if combinations are unavoidable, start lower and increase follow-up frequency to reduce falls and driving risk.

Other Useful Information

• Favor CBT-I first and treat suvorexant as a time-limited adjunct with ongoing reassessment.
• Avoid in narcolepsy and be cautious in older adults and serious mental illness with polypharmacy.
• If insomnia persists, assess for untreated sleep apnea, circadian rhythm disorders, stimulant use, alcohol/cannabis use, and mood episodes before adding additional sedatives.
• Use short prescriptions with planned follow-up; discontinue if REM intrusion symptoms, next-day impairment, or unsafe nighttime behaviors occur.

References

1. Belsomra (suvorexant) 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)