Is Quviviq (daridorexant) safer than Lunesta (eszopiclone) for older adults?

Quviviq (Daridorexant) is Safer Than Lunesta (Eszopiclone) for Older Adults

Quviviq (daridorexant) is safer than Lunesta (eszopiclone) for older adults with insomnia due to fewer cognitive side effects, lower risk of falls, and demonstrated safety in clinical trials specifically involving elderly populations.

Comparative Safety Profile

Eszopiclone (Lunesta) Concerns in Older Adults

• The American Geriatrics Society Beers Criteria® identifies nonbenzodiazepine hypnotics (including eszopiclone) as potentially inappropriate medications for older adults 1
• Eszopiclone and other "Z-drugs" are associated with:
  • Increased risk of falls and fractures
  • Cognitive impairment
  • Next-morning impairment
  • Possible increased mortality risk

Daridorexant (Quviviq) Advantages

• Clinical trials specifically demonstrated safety in older adults (≥65 years) 2, 3
• Key findings from research on daridorexant in older adults:
  • Similar or lower frequency of falls compared to placebo 2
  • No increased risk of adverse events in older adults compared to younger adults 2
  • Only one reported case of sleep paralysis and no cases of complex sleep behaviors in older adults 2
  • Well-tolerated across multiple studies 4, 5, 3

Mechanism of Action Differences

The safety advantage of daridorexant stems from its mechanism of action:

1. Daridorexant (Quviviq):

   • Dual orexin receptor antagonist (DORA) 6
   • Works by reducing wake drive rather than enhancing sedation 4
   • Designed with a half-life to minimize residual effects that might impair daytime functioning 6

2. Eszopiclone (Lunesta):

   • Nonbenzodiazepine benzodiazepine receptor agonist 1
   • Acts on GABA receptors, causing broader CNS depression
   • Associated with confusion, impaired motor performance, and anterograde amnesia 1

Clinical Evidence for Older Adults

Daridorexant Studies in Elderly

• In a randomized trial of adults ≥65 years with insomnia (n=58), daridorexant was well-tolerated with minimal side effects 3
• A secondary analysis of phase III trials showed:
  • Similar efficacy in older (≥65) and younger adults
  • No need to decrease dose for older patients
  • No increased risk of adverse events in older adults 2

Eszopiclone Concerns

• The American College of Physicians clinical practice guideline notes that hypnotic drugs may be associated with serious adverse effects in older adults, including dementia, serious injury, and fractures 1
• The 2019 AGS Beers Criteria® specifically warns against nonbenzodiazepine hypnotics (including eszopiclone) in older adults 1

Common Side Effects Comparison

Daridorexant (Quviviq)

• Most common adverse events: fatigue, nasopharyngitis, gait disturbance, and headache (≤7% in any group) 3
• Most adverse events were mild in severity 4
• Adverse event rates were not dose-dependent 4

Eszopiclone (Lunesta) and Similar Agents

• Higher rates of confusion, impaired motor performance, anterograde amnesia, and daytime sleepiness 1
• FDA warnings about daytime impairment, "sleep driving," and behavioral abnormalities 1

Practical Considerations

When considering medication for insomnia in older adults:

1. First-line approach: Cognitive behavioral therapy for insomnia (CBT-I) should be the first-line treatment 1

2. If medication is necessary:

   • Daridorexant 50 mg showed efficacy in older adults without requiring dose reduction 2
   • No evidence of increased morning sleepiness with daridorexant in older adults 2
   • Daridorexant improved daytime functioning in older adults 2

3. Special considerations:

   • The National Comprehensive Cancer Network advises against benzodiazepines and cautions against zolpidem in older patients due to cognitive impairment risk 7
   • Similar caution applies to eszopiclone and other Z-drugs

Conclusion

Based on the most recent and highest quality evidence, daridorexant (Quviviq) offers a safer alternative to eszopiclone (Lunesta) for older adults with insomnia. Its orexin receptor antagonist mechanism provides effective insomnia treatment with fewer cognitive side effects, lower fall risk, and better overall safety profile in the elderly population.