Real-World Effectiveness of Ramelteon and Suvorexant for Delirium Prevention in 948 Patients With Delirium Risk Factors

Hatta, Kotaro; Kishi, Yasuhiro; Wada, Ken; Takeuchi, Takashi; Hashimoto, Naoko; Suda, K; Taira, Toshihiro; Tsuchida, Kazuo; Ohmori, Takashi; Akizuki, Nobuya; Nishio, Y.; Nakanishi, Yukiko; Usui, Chie; Kurata, Akiko; Horikawa, Naoki; Eguchi, Hiroshi; Ito, Sayuri; Muto, Hitoshi; Nakamura, Hiroyuki; Uchimura, Naohisa

doi:10.4088/jcp.19m12865

Cited by 40 publications

(50 citation statements)

References 28 publications

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“…Finally, 7 studies (suvorexant treatment group, n = 402; control group, n = 487) were included in our meta-analysis. [ 16 – 21 , 24 ]…”

Section: Resultsmentioning

confidence: 99%

“…Three studies were designed as prospective RCTs, [ 17 , 20 , 24 ] while the other 4 were retrospective case-control studies. [ 16 , 18 , 19 , 21 ] Two trials were performed for patients in ICU, [ 19 , 20 ] 4 for non-ICU population [ 16 , 18 , 21 , 24 ] and 1 included both of the ICU and non-ICU patients. [ 17 ] The average daily dose was 15 or 20 mg.…”

Section: Resultsmentioning

confidence: 99%

“…In addition to studies by Hatta et al, [ 17 , 24 ] the control group in the remaining 5 studies underwent treatment with other sleep inducers (such as ramelteon, zolpidem, rilmazafone, etizolam, brotizolam, flunitrazepam, or diazepam). Delirium was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) in 4 studies, [ 17 , 20 , 21 , 24 ] Confusion Assessment Method for Intensive Care Unit (CAM-ICU) in 2 studies [ 18 , 19 ] and Intensive Care Delirium Screening Checklist (ICDSC) in 1 study. [ 16 ] The total NOS scores varied from 8 to 9, indicating all eligible studies of high-quality (Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…All 7 studies evaluated the prevention effects of suvorexant on the incidence of delirium [ 16 – 21 , 24 ] (Table 3 ). A fixed-effect model was used for the meta-analysis because there was no heterogeneity present among the studies ( I 2 = 15.9%, P = .311).…”

Section: Resultsmentioning

confidence: 99%

“…This hypothesis was proved by previous studies which investigated the improvement in sleep and delirium simultaneously. [ 18 , 24 , 30 ] In addition, orexin was reported to increase sympathetic nerve activity by promoting expression of pro-inflammatory cytokines [interleukin (IL)-1β, 2.7-fold; IL-6, 1.7-fold; tumor necrosis factor-α, 1.5-fold] [ 31 ] ; while there was also a strong relationship between inflammatory factors and delirium incidence (such as high C-reactive protein: relative risk, 3.0; 95% CI, 1.4–6.7 [ 32 ] ; IL-6: OR, 1.61; 95%CI, 1.00–2.58, P = .04 [ 33 ] ). Hereby, suvorexant may also exert preventative effects for delirium by inhibiting the inflammatory pathways.…”

Section: Discussionmentioning

confidence: 99%

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Suvorexant for the prevention of delirium

Xu¹,

Cui²,

Shen

et al. 2020

Medicine

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Background: Delirium is a frequently encountered complication, which is associated with increased mortality. Suvorexant, an approved agent for the treatment of insomnia, is recently suggested to be also effective for prevention of delirium by some authors. However, a consensus has yet to be reached. The goal of this study was to perform a meta-analysis to overall estimate the effectiveness of suvorexant in preventing delirium and its related consequences. Methods: Eligible studies were identified by searching online databases of PubMed, EMBASE, and Cochrane Library. The pooled OR was calculated for binary outcomes (e.g., the incidence of delirium, mortality, or adverse events), while standardized mean difference (SMD) were expressed for continuous outcomes (e.g., time to delirium onset, length of stay in hospital and ICU, time on ventilation). Results: Seven studies which comprised 402 suvorexant treatment patients and 487 patients with control treatment were included in this meta-analysis. Overall, pooled analysis indicated the incidence of delirium could be significantly reduced (OR, 0.30; P < .001) and time to delirium onset was significantly lengthened (SMD, 0.44; P = .006) in patients undergoing suvorexant treatment compared with controls. Suvorexant had no beneficial effects on the secondary outcomes [length of stay in hospital (SMD, −0.65; P = .161) and ICU (SMD, 0.34; P = .297), time on ventilation (SMD, 1.09; P = .318), drug-related adverse events (OR, drug-related adverse events (OR, 1.66; P = .319) and mortality (OR, 2.21; P = .261)]. Subgroup analysis also confirmed the benefit of suvorexant on the development of delirium, which was significant in any subgroup. Conclusion: Suvorexant should be recommended for the prevention of delirium in clinic.

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“…Finally, 7 studies (suvorexant treatment group, n = 402; control group, n = 487) were included in our meta-analysis. [ 16 – 21 , 24 ]…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Suvorexant for the prevention of delirium

Xu¹,

Cui²,

Shen

et al. 2020

Medicine

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Predisposing and Precipitating Factors Associated With Delirium

et al. 2023

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ImportanceDespite discrete etiologies leading to delirium, it is treated as a common end point in hospital and in clinical trials, and delirium research may be hampered by the attempt to treat all instances of delirium similarly, leaving delirium management as an unmet need. An individualized approach based on unique patterns of delirium pathophysiology, as reflected in predisposing factors and precipitants, may be necessary, but there exists no accepted method of grouping delirium into distinct etiologic subgroups.ObjectiveTo conduct a systematic review to identify potential predisposing and precipitating factors associated with delirium in adult patients agnostic to setting.Evidence ReviewA literature search was performed of PubMed, Embase, Web of Science, and PsycINFO from database inception to December 2021 using search Medical Subject Headings (MeSH) terms consciousness disorders, confusion, causality, and disease susceptibility, with constraints of cohort or case-control studies. Two reviewers selected studies that met the following criteria for inclusion: published in English, prospective cohort or case-control study, at least 50 participants, delirium assessment in person by a physician or trained research personnel using a reference standard, and results including a multivariable model to identify independent factors associated with delirium.FindingsA total of 315 studies were included with a mean (SD) Newcastle-Ottawa Scale score of 8.3 (0.8) out of 9. Across 101 144 patients (50 006 [50.0%] male and 49 766 [49.1%] female patients) represented (24 015 with delirium), studies reported 33 predisposing and 112 precipitating factors associated with delirium. There was a diversity of factors associated with delirium, with substantial physiological heterogeneity.Conclusions and RelevanceIn this systematic review, a comprehensive list of potential predisposing and precipitating factors associated with delirium was found across all clinical settings. These findings may be used to inform more precise study of delirium’s heterogeneous pathophysiology and treatment.

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Suvorexant for Reduction of Delirium in Older Adults After Hospitalization

Hatta,

Kishi,

Wada

et al. 2024

JAMA Netw Open

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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

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Real-World Effectiveness of Ramelteon and Suvorexant for Delirium Prevention in 948 Patients With Delirium Risk Factors

Cited by 40 publications

References 28 publications

Suvorexant for the prevention of delirium

Suvorexant for the prevention of delirium

Predisposing and Precipitating Factors Associated With Delirium

Suvorexant for Reduction of Delirium in Older Adults After Hospitalization

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