What is the most efficacious dual receptor orexin antagonist for the treatment of insomnia?

From the Guidelines

Suvorexant is currently considered the most efficacious dual orexin receptor antagonist (DORA) for treating insomnia, with a recommended starting dose of 10 mg taken once nightly within 30 minutes of bedtime, with at least 7 hours remaining before planned awakening, as supported by moderate-strength evidence from studies such as 1 and 1.

Key Points

• The dose can be increased to a maximum of 20 mg if needed, as shown in studies 1 and 1.
• Suvorexant works by blocking both orexin receptors (OX1R and OX2R), which inhibits the wake-promoting effects of orexin neuropeptides in the brain, offering advantages such as less next-day impairment, less tolerance development, and minimal rebound insomnia upon discontinuation, as noted in 1 and 1.
• Suvorexant is particularly effective for sleep maintenance insomnia and has demonstrated sustained efficacy for up to one year of nightly use, as reported in 1 and 1.
• Patients should avoid alcohol consumption while taking suvorexant, as this combination can increase sedation, and the medication should be taken on an empty stomach for optimal absorption, with common side effects including daytime somnolence, headache, and abnormal dreams, as mentioned in 1 and 1.

Mechanism and Efficacy

• Suvorexant's mechanism of action differs from traditional sleep medications like benzodiazepines and Z-drugs, potentially offering advantages such as less next-day impairment, less tolerance development, and minimal rebound insomnia upon discontinuation, as discussed in 1 and 1.
• The medication has demonstrated efficacy in improving sleep quality, reducing sleep latency, and increasing sleep duration, as shown in studies 1, 1, and 1.

Safety and Tolerability

• Suvorexant is generally well-tolerated, with common side effects including daytime somnolence, headache, and abnormal dreams, as reported in 1 and 1.
• The medication is not a controlled substance, though it still requires prescription, as noted in 1 and 1.

From the FDA Drug Label

BELSOMRA is an orexin receptor antagonist indicated for the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance (1). The mechanism of action of suvorexant in the treatment of insomnia is presumed to be through antagonism of orexin receptors. Suvorexant binds to orexin receptors, OX1R and OX2R (Ki= 0.55 and 0. 35 nM, respectively).

The most efficacious dual receptor orexin antagonist for the treatment of insomnia is suvorexant 2.

• Key points:
  • Indication: treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance
  • Mechanism of action: antagonism of orexin receptors
  • Binding: suvorexant binds to orexin receptors, OX1R and OX2R However, the FDA label does not provide a direct comparison with other dual receptor orexin antagonists to conclusively determine the most efficacious one.

From the Research

Dual Receptor Orexin Antagonists for Insomnia Treatment

• Suvorexant is a dual orexin receptor antagonist that has been shown to be effective in the treatment of insomnia, improving subjective total sleep time, wake after sleep onset, and latency to persistent sleep 3, 4, 5, 6.
• Clinical trials have demonstrated that suvorexant is relatively safe and effective for the treatment of both sleep onset and sleep maintenance insomnia at doses of 20 mg or less 3, 4.
• A systematic review and meta-analysis found that suvorexant was associated with significant improvements in subjective time to sleep onset, subjective total sleep time, and subjective quality of sleep at 1 and 3 months 4.
• Another study found that suvorexant helps improve sleep in patients with comorbidities such as obstructive sleep apnea, Alzheimer's disease, dementia, acute stroke, and delirium 5.
• A network meta-analysis compared the efficacy of different dual orexin receptor antagonists, including suvorexant and lemborexant, and found that both were effective in improving sleep outcomes, with lemborexant 10mg providing the largest reduction in wake time after sleep onset 7.

Comparison of Dual Receptor Orexin Antagonists

• Suvorexant and lemborexant are both dual orexin receptor antagonists that have been shown to be effective in the treatment of insomnia 5, 7.
• A network meta-analysis found that lemborexant 10mg provided the largest reduction in wake time after sleep onset, followed by suvorexant 20/15mg 7.
• The most frequent adverse events associated with dual orexin receptor antagonists are somnolence, nasopharyngitis, and headache, with rates of up to 14.8% 7.

Efficacy and Safety of Suvorexant

• Suvorexant has been shown to be effective in improving sleep outcomes, including subjective total sleep time, wake after sleep onset, and latency to persistent sleep 3, 4, 5, 6.
• Suvorexant is relatively safe and effective for the treatment of both sleep onset and sleep maintenance insomnia at doses of 20 mg or less 3, 4.
• The most common adverse effects associated with suvorexant are dizziness, somnolence, headaches, and cognitive impairment 5.