July 27, 2020

Lemborexant: Is it the Newest Wonder Drug for Insomnia in the Elderly?

UAMS logo

By Hayley Harrington, PharmD candidate and Lisa C. Hutchison, PharmD, MPH, BCPS, BCGP
University of Arkansas for Medical Sciences (UAMS) College of Pharmacy

 

Many older adults suffer from insomnia and struggle to find a treatment that works for them. 1 Untreated insomnia can increase the risk of cognitive impairment, cardiovascular disease, depression, and metabolic syndrome. 1  Nonpharmacologic approaches such as improving sleep hygiene, relaxation techniques, and cognitive behavioral therapy are first line treatments for insomnia, especially in older adults. 1,2  When these methods fail, healthcare providers turn to pharmacologic interventions. The options for medication include benzodiazepines, nonbenzodiazepines, sedating antidepressants, melatonin receptor agonists, and orexin receptor antagonists, 1,2,7  The newest insomnia medication is an orexin receptor antagonist called lemborexant (Dayvigo). This medication was evaluated in two drug company-sponsored randomized control trials, SUNRISE 1 and SUNRISE 2, and compared to suvorexant (Belsomra), the only other orexin receptor antagonist on the market, in a meta-analysis.

The SUNRISE 1 study compared lemborexant 5 mg to placebo on sleep onset in patients 55 years and older with insomnia disorder. 3  The results showed a statistically significant reduction in sleep onset after one month of treatment with lemborexant when compared with placebo (least square mean (LSM) for lemborexant vs. placebo, 0.77; 95% CI, 0.67-0.89; P<0.001). The mean change in sleep efficiency (LSM for lemborexant vs. placebo, 7.1%; 95% CI, 5.6-8.5%; P<0.001) and wake-after-sleep onset (WASO) (LSM lemborexant vs. placebo, -24.0 min; 95% CI, -30.0 to -18.0 min; P <0.001) were significantly better for patients taking lemborexant.  This study also compared lemborexant to zolpidem 6.25 mg (Ambien CR) for WASO during the second half of the night. Lemborexant showed a statistically significant improvement over zolpidem extended release for this value (LSM lemborexant vs. zolpidem, -6.7 min; 95% CI, -11.2 to -2.2 min; P = 0.004). However, lemborexant also showed increased occurrence of next day drowsiness when compared to placebo and zolpidem.

SUNRISE 2 evaluated change in patient reported sleep onset after 6 months of treatment with either lemborexant 5 mg or placebo. 4,6 The median age of subjects in this study was 55 (range of 19-88) and 28% were ≥ 65 years. This study found statistically significant improvements in sleep onset (LSM lemborexant vs. placebo, 0.7; 95% CI, 0.6-0.8; P <0.0001), as well as the secondary endpoints of sleep efficiency (LSM lemborexant vs. placebo, 4.5%; 95% CI, 2.2-6.9; P <0.0001) and wake after sleep onset (LSM lemborexant vs. placebo, -17.5 min; 95% CI, -27.3 to -7.6 min; P<0.0005).

A systemic review and network meta-analysis, which included four double-bind, randomized control trials (n=3237), was conducted to compare lemborexant and suvorexant in treatment of insomnia. 5,6  The 10 mg dose of lemborexant appeared more effective then suvorexant at one week, but this benefit was not seen after one month. This dose of lemborexant also showed increased occurrence of next day drowsiness compared to suvorexant. Overall, these two medications appear to be generally equivalent in subjective sleep onset, total sleep time, and WASO.

Lemborexant will be available in 5 mg and 10 mg tablets and is a schedule IV medication similar to suvorexant (see Table 1). 6,7,8   It is contraindicated in narcolepsy and comes with several warnings and precautions similar to other sedatives. 6  Lemborexant can interact with the alcohol, CYP3A4 inducers, CYP3A4 inhibitors, CNS depressants, and other medications. 6   This medication was not associated with withdrawal effects, rebound insomnia, or effects on next-day postural stability and memory. 6

Table 1. Cost and Side Effects Comparison

Medication Schedule Cost (6/26/2020) Side Effects
Lemborexant (Dayvigo) IV $11/tablet Drowsiness

Fatigue

Headache

Suvorexant

(Belsomra)

 

IV

$14.63/tablet Headache

Drowsiness

Dizziness

Zolpidem

(Ambien, Ambien CR, generics for both)

 

IV

<$10/tablet

(generics)

 

 

Headache

Drowsiness

Dizziness

Nausea

Anxiety

Hallucinations

Memory impairment

 

In summary, although lemborexant has shown benefits in insomnia, the studies also show increased risk of next day drowsiness when compared to zolpidem and suvorexant. 3,4,5   Because of this side effect and the warnings associated with this medication, it is NOT a new wonder drug to treat insomnia in the elderly. However, it is another medication to consider when trying to help patients manage this condition.

 

 

References:

  1. Patel D, Steinberg J, Patel P. Insomnia in the Elderly: A Review. Journal of Clinical Sleep Medicine. 2018;14(06):1017-1024. doi:10.5664/jcsm.7172
  2. Current and Emerging Therapies for Insomnia. AJMC. https://www.ajmc.com/journals/supplement/2020/managed-care-review-on-insomnia/current-and-emerging-therapies-for-insomnia. Published 2020.
  3. Rosenberg R, Murphy P, Zammit G, et al. Comparison of Lemborexant With Placebo and Zolpidem Tartrate Extended Release for the Treatment of Older Adults With Insomnia Disorder. JAMA Network Open. 2019;2(12): e1918254. doi:10.1001/jamanetworkopen.2019.18254
  4. Long-term Study of Lemborexant in Insomnia Disorder (SUNRISE 2) – Study Results – ClinicalTrials.gov. Clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/results/NCT02952820. Published 2016. Accessed June 22, 2020.
  5. Kishi T, Nomura I, Matsuda Y, et al. Lemborexant vs suvorexant for insomnia: A systematic review and network meta-analysis. Journal of Psychiatric Research. 2020; 128:68-74. doi: 10.1016/j.jpsychires.2020.05.025
  6. Dayvigo (lemborexant) [prescribing information]. Woodcliff Lake, NJ: Eisai Inc; December 2019.
  7. Uptodate.com. https://www.uptodate.com/contents/behavioral-and-pharmacologic-therapies-for-chronic-insomnia-in-adults?search=insomnia%20elderly&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H3553718232. Published 2020. Accessed June 22, 2020.
  8. Lemborexant, Suvorexant, Zolpidem. Accessed June 26, 2020.