Suvorexant for Reduction of Delirium in Older Adults After Hospitalization

Author:

Hatta Kotaro1,Kishi Yasuhiro2,Wada Ken3,Takeuchi Takashi4,Taira Toshihiro5,Uemura Keiichi6,Ogawa Asao7,Takahashi Kanae8,Sato Asako8,Shirakawa Masayoshi8,Herring W. Joseph9,Arano Ichiro8, ,Hatta Kotaro10,Kishi Yasuhiro10,Takeuchi Takashi10,Wada Ken10,Omori Takashi10,Inoue Shinichiro10,Edahiro Satoru10,Hashimoto Satoshi10,Uemura Keiichi10,Kawasaki Yasuhiro10,Yoshimi Asuka10,Furuno Taku10,Seki Tomoe10,Matsubara Toshio10,Furutsuka Daisuke10,Kai Toshihiro10,Ishikawa Ichiro10,Matsuoka Hiromichi10,Hashimoto Chiho10,Morihara Takashi10,Kondo Tadayuki10,Wada Hisashi10,Ikeda Manabu10,Suda Shiro10,Ishii Hironobu10,Akaho Rie10,Taira Toshihiro10,Furuno Takehiko10,Morisaki Yohei10,Saito Satoru10,Ishikawa Kensuke10,Maebayashi Yoshiro10,Inamoto Atsuko10,Yamano Sumihiro10,Tamiya Hiroko10,Miki Koji10,Kishi Nobuyuki10,Mitsuyasu Hiroshi10,Suzuki Masahiro10,Yanagisawa Toru10,Fukuda Takahiro10,Kawano Jiro10,Tsuneyama Nobuto10,Iwaya Akira10,Hashijiri Koyo10,Yamamori Hidenaga10,Takayama Takeshi10,Inoue Yukiyo10,Obokata Kaoru10,Kitamura Naoya10,Sugawara Hiroko10,Yamaga Kuniaki10,Takahashi Rei10,Kidani Tomokazu10,Tamura Kazuya10,Kitaura Yuichi10

Affiliation:

1. Department of Psychiatry, Juntendo University Nerima Hospital, Tokyo, Japan

2. Department of Psychiatry, Nippon Medical School Musashikosugi Hospital, Kawasaki, Japan

3. Department of Psychiatry, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan

4. Department of Psychiatry, Tokyo Medical and Dental University Hospital, Tokyo, Japan

5. Department of Psychiatry and Psycho-Oncology, Fukuyama City Hospital, Fukuyama, Japan

6. Department of Psychiatry and Palliative Care, Tonan Hospital, Sapporo, Japan

7. Department of Psycho-Oncology, National Cancer Center Hospital East, Kashiwa, Japan

8. MDS K.K. (Merck Sharp & Dohme LLC, a subsidiary of Merck & Co Inc), Tokyo Japan

9. Merck & Co Inc, Rahway, New Jersey

10. for the Suvorexant 085 Study Group

Abstract

ImportanceDelirium 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.ObjectiveTo evaluate the orexin receptor antagonist suvorexant for reducing delirium in older adults at high risk for delirium after hospitalization.Design, Setting, and ParticipantsThis 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.InterventionParticipants 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 MeasuresDelirium, 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.ResultsThis 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 RelevanceIn 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 RegistrationClinicalTrials.gov Identifier: NCT04571944

Publisher

American Medical Association (AMA)

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