How Belsomra (Suvorexant) Works to Help Sleep
Belsomra works by blocking orexin receptors in the brain, which turns down the brain's wakefulness system rather than forcing sleep through sedation. 1, 2
Mechanism of Action
Suvorexant is a dual orexin receptor antagonist that blocks both orexin-1 and orexin-2 receptors, representing the first medication in this class approved for insomnia treatment. 1, 2
The Orexin System and Wakefulness
Orexin neuropeptides (orexin A and orexin B) are produced by neurons in the lateral hypothalamus and function as key promoters of wakefulness and arousal. 3, 2
These orexin-producing neurons regulate the sleep-wake cycle by signaling through their receptors to maintain alertness during waking hours. 2
When orexin receptors are blocked, the drive for wakefulness is reduced, allowing the natural sleep process to occur without directly inducing sedation like traditional sleep medications. 3, 2
Unique Pharmacological Approach
Unlike benzodiazepines or Z-drugs that enhance GABA activity to force sedation, suvorexant works by reducing the active promotion of wakefulness—essentially removing the "brake" on sleep rather than pushing the "accelerator" toward sedation. 4
This mechanism targets the arousal system specifically, which may explain why suvorexant has a different side effect profile compared to traditional hypnotics, with less potential for dependence or withdrawal. 3, 4
Clinical Effects on Sleep Architecture
Sleep Maintenance (Primary Benefit)
Suvorexant most effectively reduces wake after sleep onset (WASO), with objective polysomnography showing reductions of 21-28 minutes at the 20 mg dose and clinically significant reductions even at 10 mg. 5, 6
The American Academy of Sleep Medicine suggests suvorexant specifically for sleep maintenance insomnia rather than sleep onset problems, reflecting where the strongest evidence exists. 5
Sleep Onset Effects
Sleep onset improvement is dose-dependent and less robust than sleep maintenance effects—the 10 mg and 15/20 mg doses showed minimal improvements in sleep latency that failed to meet clinical significance thresholds. 5
Only the 20 mg dose demonstrated clinically significant reduction in sleep latency (22.3 minutes versus placebo), suggesting higher doses may be needed for sleep onset problems. 5
Total Sleep Time
- Objective measurements show approximately 50 minutes increase in total sleep time at 20 mg, though patient-reported improvements were more modest (5.5-10.6 minutes), indicating a disconnect between objective and subjective sleep quality. 6
Pharmacokinetics Relevant to Sleep
The 12-hour half-life is relatively long for modern hypnotics, which contributes to sustained sleep maintenance throughout the night but also raises concerns about next-day effects. 3
Time to effect may be delayed if taken with or soon after meals, so the FDA recommends taking it within 30 minutes of bedtime on an empty stomach with at least 7 hours remaining before planned awakening. 1
Peak drug levels occur higher in women and obese patients, requiring conservative dosing particularly in obese women due to increased exposure-related adverse effects. 1, 3