Orexin receptor antagonists
- DORAs reduce wake signaling rather than GABA
- Suvorexant/lemborexant/daridorexant
- Treat sleep-onset and/or maintenance insomnia
- Somnolence + next-day impairment can occur
- Avoid in narcolepsy
- Less respiratory suppression than BZDs, not zero
- CYP3A interactions matter
Class at a glance
- DORAs reduce wake signaling rather than GABA
Pharmacology
- CYP3A interactions matter
Clinical role
- Suvorexant/lemborexant/daridorexant
- Treat sleep-onset and/or maintenance insomnia
- Somnolence + next-day impairment can occur
Safety / monitoring
- Avoid in narcolepsy
- Less respiratory suppression than BZDs, not zero
Pearls
- Gains modest: fall asleep slightly sooner, sleep slightly longer
- Sleepwalking and cataplexy-like leg weakness possible
- Usable in mild–moderate COPD
- Schedule IV
Self-check
- When should Orexin receptor antagonists generally be avoided?
Narcolepsy. - What does orexin blockade reduce rather than act through GABA?
Wake signaling.
Drugs in this class (4)
Orexin receptor antagonists prescription history
Animated chart of estimated U.S. prescriptions per year, Sleep meds (1869–2026). Orexin antagonists highlighted from 2015.
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