Are orexin inhibitors, such as suvorexant (Belsomra), safe to use for treating insomnia?

Safety Profile of Orexin Inhibitors for Treating Insomnia

Orexin inhibitors such as suvorexant (Belsomra) are generally safe and effective for treating sleep maintenance insomnia, though they carry important safety considerations including potential for CNS depression, complex sleep behaviors, and neuropsychiatric effects.

Efficacy and Clinical Recommendations

• The American Academy of Sleep Medicine (AASM) suggests that clinicians use suvorexant as a treatment for sleep maintenance insomnia in adults (versus no treatment), based on trials of 10,15/20, and 20 mg doses 1
• Suvorexant is FDA-approved for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance 2
• Compared to placebo, suvorexant improves total sleep time by approximately 10 minutes and reduces wake after sleep onset by 16-28 minutes 1
• Suvorexant represents a novel option for treating chronic insomnia with its unique mechanism of action targeting the orexin system rather than GABA receptors 3, 4

Safety Considerations and Adverse Effects

• Suvorexant is a central nervous system (CNS) depressant that can impair daytime wakefulness even when used as prescribed, potentially affecting driving ability 2
• The most common adverse effect of suvorexant is somnolence, occurring in approximately 7% of patients (vs 3% for placebo) 1, 5
• FDA labeling warns of potential cognitive and behavioral changes, including amnesia, anxiety, hallucinations, and other neuropsychiatric symptoms 5, 2
• Complex sleep behaviors may occur, including sleep-walking, sleep-driving, and engaging in other activities while not fully awake, requiring immediate discontinuation if observed 2
• Sleep paralysis, hypnagogic/hypnopompic hallucinations, and cataplexy-like symptoms can occur with suvorexant use 2

Special Populations and Precautions

• Suvorexant is contraindicated in patients with narcolepsy 2
• Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, alcohol) increases the risk of CNS depression and may require dosage adjustments 2
• Suvorexant is not recommended for use with strong CYP3A inhibitors, and dosage adjustments are needed when used with moderate CYP3A inhibitors 2
• Patients with depression require careful monitoring as suvorexant may worsen depression and increase suicidal ideation 2
• Elderly patients may be at higher risk of falls due to the drowsiness caused by suvorexant 2

Advantages Over Traditional Hypnotics

• Unlike benzodiazepines and non-benzodiazepine receptor agonists, suvorexant appears to preserve natural sleep architecture, promoting more restful sleep 4, 6
• Suvorexant has demonstrated efficacy and safety over 12 months of use with a relative lack of withdrawal effects when discontinued 3
• The unique mechanism of action may represent an alternative for patients who cannot tolerate or do not benefit from traditional sleep agents 3, 6
• Suvorexant has shown minimal physical dependence, making it potentially suitable for chronic therapy 6

Clinical Application and Limitations

• Suvorexant has primarily been studied against placebo, with limited head-to-head trials comparing it directly with other FDA-approved medications for insomnia 3, 4, 7
• While effective, suvorexant is not likely to replace benzodiazepines or non-benzodiazepine receptor antagonists as first-line therapy but offers an alternative option 3
• The risk of next-day impairment increases if suvorexant is taken with less than a full night of sleep remaining, if a higher than recommended dose is taken, or if co-administered with other CNS depressants 2
• Prescribers should monitor for somnolence and CNS depressant effects, though impairment can occur without symptoms and may not be reliably detected by ordinary clinical examination 2