This article was first published on October 28, 2022. It was last reviewed and updated on October 28, 2022.
In another article on this website, we briefly discussed what the brain’s orexin system is and why it is important. Please see the following article on this website:
What is the orexin system and why is it so important?
Dual orexin receptor antagonists (DORAs)
The three Dual Orexin Receptor Antagonists (DORAs) that are FDA-approved as of October 2022 for the treatment of insomnia are (alphabetically):
– Daridorexant (Quviviq®)
– Lemborexant (Davigo®)
– Suvorexant (Belsomra®)
These currently available orexin receptor antagonists block both orexin-1 and orexin-2 receptors. That’s the reason for their being called dual orexin receptor antagonists (DORAs).
FDA indications
All 3 of the DORAs have the exact same FDA indication—the treatment of insomnia (difficulties with sleep onset and/or maintenance).
Efficacy
The DORAs have been shown in many placebo-controlled clinical trials to improve different aspects of sleep (Xue et al., 2022; Mignott et al., 2022).
Some of the key outcome measures used in the clinical trials are listed below. Note: This should not be taken to mean that every dose of the drugs was shown to be more effective than placebo for every one of these outcome measures.
Evaluated based on sleep studies (polysomnography)
– Latency to persistent sleep (LPS). This is a measure of falling asleep (“sleep induction”).
– Wakefulness after sleep onset (WASO). This is a measure of staying asleep (“sleep maintenance”).
– Total sleep time (TST)
Evaluated based on patient ratings
The subjective measures were recorded in a diary every morning by the participants. Note: the “s” before the acronyms denotes “subjective”.
– Time to sleep onset (sTSO)
– Wakefulness after sleep onset (sWASO)
– Total sleep time (sTST)
In a simple way, we can think of the most important measures, both those based on sleep studies and on self-report to be about:
– How soon they fell asleep
– How well they were able to stay asleep
– Total amount of sleep they got.
Is any one of the 3 DORAs more effective than the others? No, we don’t have any convincing reason to believe that one of these DORAs is any more effective than the others.
Ideally, to compare their efficacy against each other, we need studies in which two or more of them are studied in the same clinical trial (“head to head”). But it is not likely that anyone would finance such as study.
Next, please see the following article on this website:
Potential side effects of dual orexin receptor antagonists (DORAs)
Related Pages
Orexin receptor antagonists
What is the orexin system and why is it so important?
An overview of the dual orexin receptor antagonists (DORAs)
Potential side effects of dual orexin receptor antagonists (DORAs)
Daridorexant (Quviviq®): Basic Information
Lemborexant (Dayvigo®): Basic information
Suvorexant (Belsomra®): Basic Information
Main menu
Treatments: Main menu
References
Wu X, Xue T, Chen Z, Wang Z, Chen G. Orexin Receptor Antagonists and Insomnia. Curr Psychiatry Rep. 2022 Oct;24(10):509-521. doi: 10.1007/s11920-022-01357-w. Epub 2022 Aug 16. PMID: 35972717.
Xue T, Wu X, Chen S, Yang Y, Yan Z, Song Z, Zhang W, Zhang J, Chen Z, Wang Z. The efficacy and safety of dual orexin receptor antagonists in primary insomnia: A systematic review and network meta-analysis. Sleep Med Rev. 2022 Feb;61:101573. doi: 10.1016/j.smrv.2021.101573. Epub 2021 Nov 26. PMID: 34902823.
Daridorexant
Mignot E, Mayleben D, Fietze I, Leger D, Zammit G, Bassetti CLA, Pain S, Kinter DS, Roth T; investigators. Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. Lancet Neurol. 2022 Feb;21(2):125-139. doi: 10.1016/S1474-4422(21)00436-1. Erratum in: Lancet Neurol. 2022 Jan 20;: Erratum in: Lancet Neurol. 2022 Jun;21(6):e6. PMID: 35065036.
Lemborexant
Murphy P, Moline M, Mayleben D, Rosenberg R, Zammit G, Pinner K, Dhadda S, Hong Q, Giorgi L, Satlin A. Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of Insomnia Disorder: Results From a Bayesian, Adaptive, Randomized, Double-Blind, Placebo-Controlled Study. J Clin Sleep Med. 2017 Nov 15;13(11):1289-1299. doi: 10.5664/jcsm.6800. PMID: 29065953; PMCID: PMC5656478.
Citrome L, Juday T, Frech F, Atkins N Jr. Lemborexant for the Treatment of Insomnia: Direct and Indirect Comparisons With Other Hypnotics Using Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed. J Clin Psychiatry. 2021 Jun 1;82:20m13795. doi: 10.4088/JCP.20m13795. PMID: 34077032.
McElroy H, O’Leary B, Adena M, Campbell R, Monfared AAT, Meier G. Comparative efficacy of lemborexant and other insomnia treatments: a network meta-analysis. J Manag Care Spec Pharm. 2021 Sep;27(9):1296-1308. doi: 10.18553/jmcp.2021.21011. Epub 2021 Jun 12. PMID: 34121443.
Rosenberg R, Murphy P, Zammit G, Mayleben D, Kumar D, Dhadda S, Filippov G, LoPresti A, Moline M. Comparison of Lemborexant With Placebo and Zolpidem Tartrate Extended Release for the Treatment of Older Adults With Insomnia Disorder: A Phase 3 Randomized Clinical Trial. JAMA Netw Open. 2019 Dec 2;2(12):e1918254. doi: 10.1001/jamanetworkopen.2019.18254. Erratum in: JAMA Netw Open. 2020 Apr 1;3(4):e206497. Erratum in: JAMA Netw Open. 2021 Aug 2;4(8):e2127643. PMID: 31880796; PMCID: PMC6991236.
Suvorexant
Herring WJ, Connor KM, Ivgy-May N, Snyder E, Liu K, Snavely DB, Krystal AD, Walsh JK, Benca RM, Rosenberg R, Sangal RB, Budd K, Hutzelmann J, Leibensperger H, Froman S, Lines C, Roth T, Michelson D. Suvorexant in Patients With Insomnia: Results From Two 3-Month Randomized Controlled Clinical Trials. Biol Psychiatry. 2016 Jan 15;79(2):136-48. doi: 10.1016/j.biopsych.2014.10.003. Epub 2014 Oct 23. PMID: 25526970.
Herring WJ, Connor KM, Snyder E, Snavely DB, Zhang Y, Hutzelmann J, Matzura-Wolfe D, Benca RM, Krystal AD, Walsh JK, Lines C, Roth T, Michelson D. 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. doi: 10.1016/j.jagp.2017.03.004. Epub 2017 Mar 8. PMID: 28427826.
Herring WJ, Connor KM, Snyder E, Snavely DB, Zhang Y, Hutzelmann J, Matzura-Wolfe D, Benca RM, Krystal AD, Walsh JK, Lines C, Roth T, Michelson D. Suvorexant in Patients with Insomnia: Pooled Analyses of Three-Month Data from Phase-3 Randomized Controlled Clinical Trials. J Clin Sleep Med. 2016 Sep 15;12(9):1215-25. doi: 10.5664/jcsm.6116. PMID: 27397664; PMCID: PMC4990943.
Herring WJ, Snyder E, Budd K, Hutzelmann J, Snavely D, Liu K, Lines C, Roth T, Michelson D. Orexin receptor antagonism for treatment of insomnia: a randomized clinical trial of suvorexant. Neurology. 2012 Dec 4;79(23):2265-74. doi: 10.1212/WNL.0b013e31827688ee. Epub 2012 Nov 28. PMID: 23197752.
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