Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2024 Aug 1;7(8):e2427691.
doi: 10.1001/jamanetworkopen.2024.27691.

Suvorexant for Reduction of Delirium in Older Adults After Hospitalization: A Randomized Clinical Trial

Kotaro Hatta  1 , Yasuhiro Kishi  2 , Ken Wada  3 , Takashi Takeuchi  4 , Toshihiro Taira  5 , Keiichi Uemura  6 , Asao Ogawa  7 , Kanae Takahashi  8 , Asako Sato  8 , Masayoshi Shirakawa  8 , W Joseph Herring  9 , Ichiro Arano  8 ; Suvorexant 085 Study Group
Collaborators, Affiliations
Clinical Trial

Suvorexant for Reduction of Delirium in Older Adults After Hospitalization: A Randomized Clinical Trial

Kotaro Hatta et al. JAMA Netw Open. .

Abstract

Importance: Delirium is common among older hospitalized adults. In addition to presenting immediate management issues, delirium can increase the long-term risk of dementia, institutionalization, and mortality. Delirium is associated with disrupted sleep, and prior studies suggest that some specific sleep-promoting agents may reduce delirium.

Objective: To evaluate the orexin receptor antagonist suvorexant for reducing delirium in older adults at high risk for delirium after hospitalization.

Design, setting, and participants: This double-blind, placebo-controlled, phase 3 randomized clinical trial was conducted at 50 hospitals in Japan between October 22, 2020, and December 23, 2022. The study population included Japanese adults aged 65 to 90 years who were at high risk for delirium (mild cognitive impairment or mild dementia, history of delirium at prior hospitalization, or both) and had been hospitalized for acute disease or elective surgery. Data analysis was performed between January 23 and March 13, 2023.

Intervention: Participants were randomized 1:1 to suvorexant (15 mg) or placebo taken at bedtime for up to 7 days while in the hospital.

Main outcomes and measures: Delirium, the primary end point, was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria while participants were hospitalized. The treatment difference in the proportion of participants with delirium was analyzed.

Results: This study included 203 participants: 101 were treated with suvorexant (mean [SD] age, 81.5 [4.5]; years; 52 men [51.5%] and 49 women [48.5%]) and 102 received placebo (mean [SD] age, 82.0 [4.9] years; 45 men [44.1%] and 57 women [55.9%]). There were 17 participants with delirium (16.8%) in the suvorexant group compared with 27 (26.5%) in the placebo group (difference, -8.7% [95% CI, -20.1% to 2.6%]; P = .13). Adverse events were similar between the 2 groups.

Conclusions and relevance: In this randomized clinical trial of suvorexant in older adults at high risk for delirium after hospitalization, fewer participants taking suvorexant had delirium compared with placebo, but the difference was not statistically significant. Further studies are needed to determine whether suvorexant may be useful for reducing delirium, particularly delirium with a hyperactive component, in this population.

Trial registration: ClinicalTrials.gov Identifier: NCT04571944.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Hatta reported receiving honoraria from MSD K.K., Sumitomo Pharma, Eisai, Janssen Pharmaceuticals, Meiji Seika, and Otsuka Pharmaceutical as well as consulting fees from Hisamitsu Pharmaceutical and GEXVal outside the submitted work. Dr Kishi reported receiving personal fees from MSD during the conduct of the study. In addition, Dr Kishi reported receiving personal fees from Jansen Pharmaceuticals, GlaxoSmithKline, Otsuka Pharmaceutical, Eisai, Sumitomo Pharma, Daiichi Sankyo, Meiji, Takeda, and Hisamitsu Pharmaceutical outside the submitted work. Dr Wada reported receiving honoraria from Otsuka Pharmaceutical, Eizai, MSD, Sumitomo Pharma, Viatris, Takeda, and Yoshitomi outside the submitted work. Dr Takeuchi reported receiving personal fees from Otsuka Pharmaceutical, MSD, Sumitomo Pharma, Meiji Seika Pharma, Viatris, Eisai, Takeda Pharmaceutical, and Towa Pharmaceutical outside the submitted work. Dr Taira reported receiving grants from MSD K.K. during the conduct of the study and personal fees from MSD K.K. outside the submitted work. Dr Uemura reported receiving personal fees from Eisai, EA Pharma, MSD, Viatris, Sumitomo Pharma, Meiji Seika Pharma, Daiichi Sankyo, Maylan, Tsumura, Hisamitsu Pharmaceutical, Kyowa Kirin, Otsuka Pharmaceutical, Takeda Pharmaceutical, Janssen Pharmaceutical, and Astellas Pharma outside the submitted work. Dr Ogawa reported receiving personal fees from Eisai, Chugai, Daiichi Sankyo, Eli Lilly, Otsuka, Ono, MSD, Pfizer, Hisamitsu, Astellas, Novartis, and Meiji outside the submitted work. Ms Takahashi reported being employed by MSD K.K. during the conduct of the study. Ms Sato reported being employed by MSD K.K. during the conduct of the study. Mr Shirakawa reported being employed by and receiving fees from MSD K.K. outside the submitted work. Dr Herring reported being employed by Merck & Co Inc during the conduct of the study. Dr Arano reported being employed by MSD K.K. during the conduct of the study.

Figures

Figure 1.
Figure 1.. Trial Flow Diagram
Figure 2.
Figure 2.. Kaplan-Meier Plot of Time to Delirium
Tick marks indicate censored data.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; 2013.
    1. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014;383(9920):911-922. doi:10.1016/S0140-6736(13)60688-1 - DOI - PMC - PubMed
    1. Watt J, Tricco AC, Talbot-Hamon C, et al. . Identifying older adults at risk of delirium following elective surgery: a systematic review and meta-analysis. J Gen Intern Med. 2018;33(4):500-509. doi:10.1007/s11606-017-4204-x - DOI - PMC - PubMed
    1. Igarashi M, Okuyama K, Ueda N, et al. . Incremental medical cost of delirium in elderly patients with cognitive impairment: analysis of a nationwide administrative database in Japan. BMJ Open. 2022;12(12):e062141. doi:10.1136/bmjopen-2022-062141 - DOI - PMC - PubMed
    1. Witlox J, Eurelings LS, de Jonghe JF, Kalisvaart KJ, Eikelenboom P, van Gool WA. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA. 2010;304(4):443-451. doi:10.1001/jama.2010.1013 - DOI - PubMed

Publication types

Associated data