Suvorexant for Reduction of Delirium in Older Adults After Hospitalization
Authors: Hatta Kotaro , Kishi Yasuhiro , Wada Ken , Takeuchi Takashi , Taira Toshihiro , Uemura Keiichi , Ogawa Asao , Takahashi Kanae , Sato Asako , Shirakawa Masayoshi , Herring W. Joseph , Arano Ichiro ,   Suvorexant 085 Study Group, Hatta Kotaro , Kishi Yasuhiro , Takeuchi Takashi , Wada Ken , Omori Takashi , Inoue Shinichiro , Edahiro Satoru , Hashimoto Satoshi , Uemura Keiichi , Kawasaki Yasuhiro , Yoshimi Asuka , Furuno Taku , Seki Tomoe , Matsubara Toshio , Furutsuka Daisuke , Kai Toshihiro , Ishikawa Ichiro , Matsuoka Hiromichi , Hashimoto Chiho , Morihara Takashi , Kondo Tadayuki , Wada Hisashi , Ikeda Manabu , Suda Shiro , Ishii Hironobu , Akaho Rie , Taira Toshihiro , Furuno Takehiko , Morisaki Yohei , Saito Satoru , Ishikawa Kensuke , Maebayashi Yoshiro , Inamoto Atsuko , Yamano Sumihiro , Tamiya Hiroko , Miki Koji , Kishi Nobuyuki , Mitsuyasu Hiroshi , Suzuki Masahiro , Yanagisawa Toru , Fukuda Takahiro , Kawano Jiro , Tsuneyama Nobuto , Iwaya Akira , Hashijiri Koyo , Yamamori Hidenaga , Takayama Takeshi , Inoue Yukiyo , Obokata Kaoru , Kitamura Naoya , Sugawara Hiroko , Yamaga Kuniaki , Takahashi Rei , Kidani Tomokazu , Tamura Kazuya , Kitaura Yuichi 
Published: August 2024

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