EFFICACY AND SAFETY OF LEMBOREXANT IN ELDERLY PATIENTS WITH INSOMNIA DISORDER: A RANDOMIZED CONTROLLED STUDY
DOI:
https://doi.org/10.48047/rh8h0912Keywords:
Insomnia disorder, Lemborexant, Dual orexin receptor antagonist, Elderly population, PolysomnographyAbstract
Insomnia disorder is very common in the older adults and tends to be accompanied with poor functioning during the day and likelihood of adverse outcomes. Hypnotics like benzodiazepines and Z-drugs are contraindicated because of their side effects on safety in older patients. This was a randomized, double-blind, placebo-controlled trial that compared the effectiveness and safety of a dual orexin receptor antagonist, lemborexant, in patients with insomnia disorder aged 55 years and above. One thousand one hundred subjects were randomized to get lemborexant 5 mg, lemborexant 10 mg, zolpidem extended-release 6.25 mg and placebo during 30 nights. There were subjective and polysomnographic outcomes of sleep. Both lemborexant doses showed a significant improvement in the sleep onset, sleep maintenance and sleep efficiency among the placebo and zolpidem in terms of effects lasting one month. The severity of insomnia and the functioning in the daytime were also improved significantly. There was an overall positive safety profile of lemborexant and it was generally well tolerated.
Downloads
References
Rodriguez JC, Dzierzewski JM, Alessi CA. Sleep problems in the elderly. Med Clin North Am. 2015;99(2):-. doi: 10.1016/j.mcna.2014.11.013
Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med. 2008;4(5):487-504.
Morin CM, Colecchi C, Stone J, Sood R, Brink D. Behavioral and pharmacological therapies for late-life insomnia: a randomized controlled trial. JAMA. 1999;281(11):991-999. doi: 10.1001/jama.281.11.991
Buenaver LF, Townsend D, Ong JC. Delivering cognitive behavioral therapy for insomnia in the real world: considerations and controversies. Sleep Med Clin. 2019;14(2):275-281. doi: 10.1016/j.jsmc.2019.01.008
Cooke JR, Ancoli-Israel S. Normal and abnormal sleep in the elderly. Handb Clin Neurol. 2011;98:653-665. doi: 10.1016/B978-0-444-52006-7.00041-1
Matheson E, Hainer BL. Insomnia: pharmacologic therapy. Am Fam Physician. 2017;96(1):29-35.
Hohagen F, Kappler C, Schramm E, Riemann D, Weyerer S, Berger M. Sleep onset insomnia, sleep maintaining insomnia and insomnia with early morning awakening—temporal stability of subtypes in a longitudinal study on general practice attenders. Sleep. 1994;17(6):551-554.
Glass J, Lanctot KL, Herrmann N, Sproule BA, Busto UE. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ. 2005;331(7526):1169. doi: 10.1136/bmj.38623.768588.47
Schroeck JL, Ford J, Conway EL, et al. Review of safety and efficacy of sleep medicines in older adults. Clin Ther. 2016;38(11):2340-2372. doi: 10.1016/j.clinthera.2016.09.010
Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13(2):307-349. doi: 10.5664/jcsm.6470
American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227-2246. doi: 10.1111/jgs.13702
Wang C, Wang Q, Ji B, et al. The orexin/receptor system: molecular mechanism and therapeutic potential for neurological diseases. Front Mol Neurosci. 2018;11:220. doi: 10.3389/fnmol.2018.00220
Beuckmann CT, Suzuki M, Ueno T, Nagaoka K, Arai T, Higashiyama H. In vitro and in silico characterization of lemborexant (E2006), a novel dual orexin receptor antagonist. J Pharmacol Exp Ther. 2017;362(2):287-295. doi: 10.1124/jpet.117.241422
Murphy P, Moline M, Mayleben D, et al. 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;13(11):1289-1299. doi: 10.5664/jcsm.6800
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH Harmonised Tripartite Guideline. Guideline for Good Clinical Practice E6 (R1). https://apps.who.int/medicinedocs/documents/s22154en/s22154en.pdf. Published June 10, 1996. Accessed November 8, 2019.
World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191-2194. doi: 10.1001/jama.2013.281053
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013. https://dsm.psychiatryonline.org/doi/book/10.1176/appi.books.9780890425596. Accessed January 7, 2019.
Ambien CR tablets [package insert]. Bridgewater, NJ: Sanofi-Aventis US LLC; 2014.
Bastien CH, Vallières A, Morin CM. Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med. 2001;2(4):297-307. doi: 10.1016/S1389-9457(00)00065-4
Tyrer P, Murphy S, Riley P. The benzodiazepine withdrawal symptom questionnaire. J Affect Disord. 1990;19(1):53-61. doi: 10.1016/0165-0327(90)90009-W
Ohayon MM, Carskadon MA, Guilleminault C, Vitiello MV. Meta-analysis of quantitative sleep parameters from childhood to old age in healthy individuals: developing normative sleep values across the human lifespan. Sleep. 2004;27(7):1255-1273. doi: 10.1093/sleep/27.7.1255
Walsh JK, Soubrane C, Roth T. Efficacy and safety of zolpidem extended release in elderly primary insomnia patients. Am J Geriatr Psychiatry. 2008;16(1):44-57. doi: 10.1097/JGP.0b013e3181256b01
Herring WJ, Connor KM, Snyder E, et al. Suvorexant in patients with insomnia: pooled analyses of three-month data from phase-3 randomized controlled clinical trials. J Clin Sleep Med. 2016;12(9):1215-1225. doi: 10.5664/jcsm.6116.
Downloads
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format for any purpose, even commercially.
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
- The licensor cannot revoke these freedoms as long as you follow the license terms.
Under the following terms:
- Attribution — You must give appropriate credit , provide a link to the license, and indicate if changes were made . You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
Notices:
You do not have to comply with the license for elements of the material in the public domain or where your use is permitted by an applicable exception or limitation .
No warranties are given. The license may not give you all of the permissions necessary for your intended use. For example, other rights such as publicity, privacy, or moral rights may limit how you use the material.
