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Name: Suvorexant
Synonyms: Belsomra, MK-4305
Chemical Name: [(7R)-4-(5-chloro-1,3-benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-yl][5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]methanone
Therapy Type: Small Molecule (timeline)
Target Type: Other (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Approved)
Company: Merck
Approved for: Insomnia, Insomnia in mild to moderate Alzheimer's disease


This orexin receptor antagonist was approved by the U.S. FDA in 2014 to treat insomnia. In February 2020, Suvorexant became the first medication to be approved for treating sleep disorders in Alzheimer’s disease (company press releaseFDA prescribing information). Suvorexant is taken by mouth.

Suvorexant was reported to have a lower potential for abuse, and be generally safer, than other sleep medications frequently used in aging populations, such as benzodiazepines (Okino et al., 2023Moline et al., 2023Pan et al., 2023Katsuta et al., 2023).

Orexin is a neuropeptide produced by the hypothalamus. It promotes wakefulness, and blocking its receptor promotes sleep. 

Many people with AD suffer from disruption of circadian rhythms that leads to poor sleep, nighttime activity and daytime sleepiness. Circadian disruption is a frequent cause of institutionalization (Harper et al., 2005). Changes in sleep/wake cycles also occur in preclinical AD, and are linked to increased amyloid deposition and risk of cognitive decline (Oct 2013 news; Ju et al., 2013; Musiek et al., 2018). Thus, sleep aids are of interest as potential disease modifiers. CSF orexin levels are elevated in Alzheimer's disease (Oct 2014 news).

In the APP/PS1 mouse model of AD, suvorexant was shown to improve circadian rhythms and cognitive function, restore hippocampal synaptic plasticity, and reduce Aβ plaque deposition in hippocampus and cortex (Zhou et al., 2020).


In May 2016, Merck began a Phase 3 trial to test whether suvorexant would ease sleep disturbances in 285 people with mild to moderate AD and insomnia. Participants took placebo for two weeks, followed by a baseline overnight polysomnography sleep study. They were then randomized to suvorexant or placebo for four weeks, starting at 10 mg daily and escalating after two weeks to 20 mg as tolerated. After four weeks, participants underwent a final overnight polysomnography session.

In May 2019, company scientists presented results at the American Academy of Neurology meeting (May 2019 conference news). Suvorexant was efficacious on both primary outcomes. It lengthened total nighttime sleep time by 28 minutes compared with placebo, and shortened nighttime waking time by 15 minutes. Importantly, suvorexant did not impair cognition. Adverse events occurred in fewer than 5 percent of participants, and included daytime drowsiness, dry mouth, and falls. Trial data are published (Herring et al., 2020).

In late 2016, a study conducted at Washington University, St. Louis, started to measure whether improving sleep efficiency with suvorexant affects CSF Aβ. Thirty-eight cognitively normal participants took 10 or 20 mg suvorexant or placebo on two consecutive nights, and slept in a research hospital while undergoing repeated CSF sampling to monitor Aβ production, clearance, and concentration, and tau levels. The study was completed in March 2021. According to published results, 20 mg suvorexant decreased the phospho-tau181/tau ratio by 10-15 percent within hours, but did not affect p-tau202 or p-tau217 to tau ratios. The drug lowered Aβ by 10 to 20 percent compared to placebo starting five hours after dosing (Lucey et al., 2023).

In May 2022, a Phase 2 study began at Washington University to assess the effect of two years of suvorexant on the accumulation of brain amyloid. The study plans to enroll 200 cognitively normal participants with PET evidence of amyloid accumulation and poor sleep, who will take 20 mg suvorexant or placebo nightly. The primary outcome will be change in brain amyloid by PET scan. Secondary outcomes include tau PET, cognitive measures, and changes in plasma and CSF markers of Aβ and tau, as well as blood and CSF transcriptomic, proteomic, and lipidomic analysis, and microbiome evaluation. Completion is anticipated in May 2026.

Suvorexant is also being evaluated for insomnia related to Parkinson’s disease, progressive supranuclear palsy, opioid and alcohol use disorder, multiple sclerosis, PTSD, major depressive disorder, and restless legs syndrome.

For details on suvorexant trials, see

Last Updated: 15 May 2023


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News Citations

  1. Drug Reported to Help Alzheimer’s Patients Sleep Better
  2. From ApoE to Zzz’s—Does Sleep Quality Affect Dementia Risk?
  3. Wake Up and Smell the … Orexin? Peptide Percolates in Alzheimer’s Brain

Paper Citations

  1. . Polysomnographic assessment of suvorexant in patients with probable Alzheimer's disease dementia and insomnia: a randomized trial. Alzheimers Dement. 2020 Mar;16(3):541-551. Epub 2020 Jan 15 PubMed.
  2. . Suvorexant Acutely Decreases Tau Phosphorylation and Aβ in the Human CNS. Ann Neurol. 2023 Jul;94(1):27-40. Epub 2023 Apr 20 PubMed.
  3. . Efficacy and safety of lemborexant as an alternative drug for patients with insomnia taking gamma-aminobutyric acid-benzodiazepine receptor agonists or suvorexant. Hum Psychopharmacol. 2023 May;38(3):e2868. Epub 2023 Apr 13 PubMed.
  4. . The abuse potential of lemborexant, a dual orexin receptor antagonist, according to the 8 factors of the Controlled Substances Act. Psychopharmacology (Berl). 2023 Apr;240(4):699-711. Epub 2023 Feb 7 PubMed.
  5. . The Comparative Effectiveness and Safety of Insomnia Drugs: A Systematic Review and Network Meta-Analysis of 153 Randomized Trials. Drugs. 2023 Mar 22; PubMed.
  6. . Safety and real-world efficacy of lemborexant in the treatment of comorbid insomnia. Sleep Med X. 2023 Dec;5:100070. Epub 2023 Mar 27 PubMed.
  7. . Disturbance of endogenous circadian rhythm in aging and Alzheimer disease. Am J Geriatr Psychiatry. 2005 May;13(5):359-68. PubMed.
  8. . Sleep quality and preclinical Alzheimer disease. JAMA Neurol. 2013 May 1;70(5):587-93. PubMed.
  9. . Circadian Rest-Activity Pattern Changes in Aging and Preclinical Alzheimer Disease. JAMA Neurol. 2018 May 1;75(5):582-590. PubMed.
  10. . Suvorexant ameliorates cognitive impairments and pathology in APP/PS1 transgenic mice. Neurobiol Aging. 2020 Jul;91:66-75. Epub 2020 Mar 3 PubMed.

External Citations

  2. company press release
  3. FDA prescribing information

Further Reading


  1. . The Discovery of Suvorexant, the First Orexin Receptor Drug for Insomnia. Annu Rev Pharmacol Toxicol. 2017 Jan 6;57:509-533. PubMed.
  2. . Review of Safety and Efficacy of Sleep Medicines in Older Adults. Clin Ther. 2016 Nov;38(11):2340-2372. Epub 2016 Oct 15 PubMed.
  3. . Considerations and Current Trends in the Management of the Geriatric Patient on a Consultation-Liaison Service. Curr Psychiatry Rep. 2020 Apr 13;22(5):21. PubMed.
  4. . Suvorexant for the treatment of insomnia in patients with Alzheimer's disease. Aust N Z J Psychiatry. 2018 Feb;52(2):207-208. Epub 2017 Dec 14 PubMed.
  5. . Suvorexant for the treatment of primary insomnia: A systematic review and meta-analysis. Sleep Med Rev. 2017 Oct;35:1-7. Epub 2016 Oct 28 PubMed.
  6. . Preventive Effects of Suvorexant on Delirium: A Randomized Placebo-Controlled Trial. J Clin Psychiatry. 2017 Sep/Oct;78(8):e970-e979. PubMed.
  7. . A Review of Suvorexant, Doxepin, Ramelteon, and Tasimelteon for the Treatment of Insomnia in Geriatric Patients. Consult Pharm. 2017 Mar 1;32(3):156-160. PubMed.
  8. . Suvorexant in Elderly Patients with Insomnia: Pooled Analyses of Data from Phase III Randomized Controlled Clinical Trials. Am J Geriatr Psychiatry. 2017 Jul;25(7):791-802. Epub 2017 Mar 8 PubMed.
  9. . Dual orexin receptor antagonists for treatment of insomnia: A systematic review and meta-analysis on randomized, double-blind, placebo-controlled trials of suvorexant and lemborexant. Front Psychiatry. 2022;13:1070522. Epub 2022 Dec 12 PubMed.
  10. . Pilot evaluation of a consumer wearable device to assess sleep in a clinical polysomnography trial of suvorexant for treating insomnia in patients with Alzheimer's disease. J Sleep Res. 2021 Dec;30(6):e13328. Epub 2021 Aug 2 PubMed.
  11. . Comparison of polysomnography in people with Alzheimer's disease and insomnia versus non-demented elderly people with insomnia. Sleep Med. 2023 Jan;101:515-521. Epub 2022 Dec 1 PubMed.
  12. . Hypocretins (orexins): The ultimate translational neuropeptides. J Intern Med. 2022 May;291(5):533-556. Epub 2022 Jan 19 PubMed.
  13. . Pharmacological and non-pharmacological interventions to enhance sleep in mild cognitive impairment and mild Alzheimer's disease: A systematic review. J Sleep Res. 2020 Dec 2;:e13229. PubMed.