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