Suvorexant
First-in-class dual orexin receptor antagonist (DORA) approved for insomnia. Promotes sleep by blocking wake-promoting orexin signalling rather than sedating via GABA, with lower dependence risk than Z-drugs but notable next-day somnolence and rare sleep paralysis / cataplexy-like effects.
01 Overview
Suvorexant (brand Belsomra) was approved by the FDA in 2014 as the first dual orexin receptor antagonist for insomnia with difficulty in sleep onset and/or maintenance. Rather than broadly depressing the CNS like benzodiazepines and Z-drugs, it selectively dampens the orexin (hypocretin) arousal system, effectively lowering wakefulness drive.
It is a Schedule IV controlled substance in the US because of measurable but low abuse potential. It improves both sleep onset and maintenance, but its relatively long half-life means next-morning driving impairment can occur, especially at higher doses, and the FDA-recommended starting dose is deliberately low.
02 Mechanism
Reversibly blocks orexin OX1 and OX2 receptors, suppressing the orexin/hypocretin wake-promoting system and lowering arousal to permit sleep.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Starting | 10 mg/day | Oral | 10 mg within 30 min of bed with >=7 h remaining; take no more than once per night. |
| Maximum | 15–20 mg/day | Oral | Max 20 mg; higher doses raise next-day impairment risk. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Improved sleep maintenanceReduces wake after sleep onset and increases total sleep time. | ~15-30 min more total sleep | Clinical | |
| Reduced sleep onset latencyModest shortening of time to fall asleep. | ~5-10 min faster | Clinical | |
| Preserved sleep architectureDoes not suppress slow-wave or REM sleep to the degree seen with GABAergic hypnotics. | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Next-day somnolence / driving impairmentResidual drowsiness and impaired next-morning driving, especially at 20 mg. | Moderate | Common, dose-dependent | Clinical | |
| Sleep paralysis / cataplexy-like weaknessTransient inability to move or speak on falling asleep/waking, and leg weakness resembling mild cataplexy. | Moderate | Uncommon | Clinical | |
| Complex sleep behavioursSleep-driving, sleep-walking, and other parasomnias with no memory of the event. | Severe | Rare | Clinical |