What is Belsomra (Suvorexant)?
Belsomra (suvorexant) is an orexin receptor antagonist FDA-approved for treating insomnia characterized by difficulties with sleep onset and/or sleep maintenance. 1
Mechanism of Action
Suvorexant works by blocking orexin receptors (OX1R and OX2R), which are responsible for promoting wakefulness and arousal. By antagonizing these receptors, it reduces arousal drive and promotes sleep through a fundamentally different mechanism than traditional hypnotics like benzodiazepines or Z-drugs. 2, 3
Clinical Efficacy
The American Academy of Sleep Medicine (2017) recommends suvorexant for treating sleep maintenance insomnia, though with a "weak" recommendation under the GRADE system. 4 The evidence shows:
- Total sleep time: Mean improvement of 10 minutes compared to placebo (95% CI: 2 to 19 minutes)
- Wake after sleep onset: Mean reduction of 16-28 minutes compared to placebo (95% CI: 7 to 43 minutes)
- Tested at doses of 10,15/20, and 20 mg
The American College of Physicians (2016) similarly found that suvorexant may improve short-term global and sleep outcomes for adults with insomnia disorder, though absolute effect sizes were small and based on low-to-moderate strength evidence. 5
Dosing
The recommended starting dose is 10 mg taken once nightly within 30 minutes of bedtime, with at least 7 hours remaining before planned awakening. 1
- Maximum dose: 20 mg once nightly
- If 10 mg is well-tolerated but ineffective, the dose can be increased
- Take on an empty stomach; food delays the effect
- Special populations: In obese women particularly, consider the increased risk of exposure-related adverse effects before dose escalation due to higher drug exposure
With moderate CYP3A inhibitors: Use 5 mg (generally should not exceed 10 mg)
With strong CYP3A inhibitors: Not recommended 1
Safety Profile
Common adverse effects include:
Important warnings 1:
- CNS depression and daytime impairment: Can impair driving ability and increase fall risk; effects may persist for several days after discontinuation
- Contraindicated in narcolepsy
- Use caution in patients at risk for REM sleep behavior disorder, depression, or delirium 6
- Dose reduction needed when combined with other CNS depressants
Critical Context
The long-term efficacy and comparative effectiveness of suvorexant versus other insomnia medications remain unknown. 5 All available studies compared suvorexant to placebo only, not to other FDA-approved sleep medications. 3
Observational data suggest hypnotics generally may be associated with increased risk for dementia, fractures, and major injury, though trial-based harms evidence was insufficient or low strength. 5 This underscores the importance of using the lowest effective dose and considering non-pharmacologic interventions like cognitive behavioral therapy for insomnia (CBT-I) as first-line treatment.
Suvorexant demonstrated efficacy over 3 months of nightly use with minimal withdrawal or rebound effects upon discontinuation, which may represent an advantage over traditional benzodiazepines. 7