Tolerance to Dayvigo (Lemborexant) for Insomnia Treatment
Based on the available evidence, tolerance to Dayvigo (lemborexant) has not been observed in clinical studies, even with long-term use up to 12 months. 1, 2
Evidence on Tolerance Development
The 2022 review in Australasian Psychiatry specifically states that "neither tolerance to sedation nor withdrawal effects on discontinuation have been observed" with lemborexant 1
A 2024 study examining lemborexant in adults ≥65 years found that improvements in sleep parameters were:
- Observed as early as the first week of treatment
- Sustained through 12 months of continuous use
- Showed no evidence of diminishing efficacy over time 2
Long-term efficacy data from clinical trials indicates that lemborexant maintains its effectiveness beyond 6 months of regular use 1
Mechanism and Pharmacological Properties
Lemborexant works as a dual orexin receptor antagonist (DORA), which differs from traditional sedative-hypnotics:
- Unlike benzodiazepines and Z-drugs that act on GABA receptors, lemborexant targets the wake-promoting orexin system 3
- This mechanism may contribute to its sustained efficacy profile
- Lemborexant has a half-life of 17-19 hours, which is longer than some other sleep medications 1
Clinical Considerations
When using lemborexant for insomnia:
- Starting dose is 5 mg, which can be increased to 10 mg if needed 1
- Should be taken at least 7 hours before planned awakening
- Common side effects include somnolence (10%), headache (2-5%), and nightmares (2-5%) 1
- Metabolized by CYP3A4/5, so potential drug interactions should be monitored 1
Safety Profile
- Lemborexant has minimal residual effects on morning alertness or next-day function 4
- Studies have shown that lemborexant does not significantly impair:
- Next-morning postural stability
- Cognitive performance (with limited exceptions)
- Driving performance 4
- In fact, morning alertness was significantly improved with lemborexant compared to placebo in long-term studies 4, 2
Important Considerations
- While tolerance has not been observed in studies up to 12 months, individual responses may vary
- Rare side effects to monitor include sleep paralysis, hypnagogic/hypnopompic hallucinations, and complex sleep behaviors 1
- As with all insomnia medications, combining lemborexant with cognitive behavioral therapy for insomnia (CBT-I) is recommended for optimal outcomes 5