Melatonin does not reduce delirium severity in hospitalized older adults: Results of a randomized placebo‐controlled trial.

Background: Delirium is common in older inpatients, causing distress, cognitive decline, and death. Current therapies are unsatisfactory, limited by lack of efficacy and adverse effects. There is an urgent need for effective delirium treatment. Sleep wake cycle is disturbed in delirium; endogenous M...

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Publicado en:Journal of the American Geriatrics Society Vol. 72; no. 6; pp. 1802 - 1810
Autores principales: Lange, Peter W., Turbić, Alisa, Soh, Cheng Hwee, Clayton‐Chubb, Daniel, Lim, Wen Kwang, Conyers, Rachel, Watson, Rosie, Maier, Andrea B.
Formato: Artículo
Publicado: Wiley-Blackwell Jun2024
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Acceso en línea:Ver este registro en EBSCOhost
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      dt: Jun2024
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      pub: Wiley-Blackwell
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        10.1111/jgs.18825
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        atl: Melatonin does not reduce delirium severity in hospitalized older adults: Results of a randomized placebo‐controlled trial.
      aug:
        au:
          Lange, Peter W.
          Turbić, Alisa
          Soh, Cheng Hwee
          Clayton‐Chubb, Daniel
          Lim, Wen Kwang
          Conyers, Rachel
          Watson, Rosie
          Maier, Andrea B.
        affil:
          Department of Aged Care and Medicine, The Royal Melbourne Hospital, Melbourne Medical School, The University of Melbourne, Parkville Victoria,, Australia
          Department of Geriatrics and General Medicine, Werribee Mercy Hospital, Werribee Victoria,, Australia
          Bone and Fractures Research Program, Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne Victoria,, Australia
          Department of Gastroenterology, Alfred Health, Prahran Victoria,, Australia
          Department of Gastroenterology, Eastern Health, Box Hill Victoria,, Australia
          Department of Medicine, Central Clinical School, Monash University, Victoria,, Australia
          Department of Paediatrics, The University of Melbourne, Parkville Victoria,, Australia
          Heart Disease, Stem Cell Biology, Murdoch Children's Research Institute, Parkville Victoria,, Australia
          Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
          Department of Human Movement Sciences, @AgeAmsterdam, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands
          Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
          Centre for Healthy Longevity, @AgeSingapore, National University Health System, Singapore, Singapore
      su:
        Placebos
        Blind experiment
        Randomized controlled trials
        Hospital care of older people
        Old age
        Controlled release preparations
        Data analysis
        Research funding
        Statistical sampling
        Severity of illness index
        Melatonin
        Oral drug administration
        Treatment effectiveness
        Tertiary care
        Descriptive statistics
        Mann Whitney U Test
        Delirium
        Statistics
        Internal medicine
        Comparative studies
        Length of stay in hospitals
        Sleep quality
        Sleep disorders
        Drug tolerance
      sug:
        subj:
          Placebos
          Blind experiment
          Randomized controlled trials
          Hospital care of older people
          Old age
          Marketing Research and Public Opinion Polling
          Specialty (except Psychiatric and Substance Abuse) Hospitals
          Controlled release preparations
          Data analysis
          Research funding
          Statistical sampling
          Severity of illness index
          Melatonin
          Oral drug administration
          Treatment effectiveness
          Tertiary care
          Descriptive statistics
          Mann Whitney U Test
          Delirium
          Statistics
          Internal medicine
          Comparative studies
          Length of stay in hospitals
          Sleep quality
          Sleep disorders
          Drug tolerance
      keyword:
        aged neurocognitive disorders
        delirium
        inpatients
        melatonin
        sepsis‐associated encephalopathy
        sleep wake disorders
        aged neurocognitive disorders
        delirium
        inpatients
        melatonin
        sepsis‐associated encephalopathy
        sleep wake disorders
      ab: Background: Delirium is common in older inpatients, causing distress, cognitive decline, and death. Current therapies are unsatisfactory, limited by lack of efficacy and adverse effects. There is an urgent need for effective delirium treatment. Sleep wake cycle is disturbed in delirium; endogenous Melatonin is perturbed, and exogenous Melatonin is a safe and effective medication for sleep disorders. This study aims to determine the effect of oral Melatonin 5 mg immediate release (IR) nightly for five nights on the severity of delirium in older (≥65 years) medical inpatients. Methods: This was a double‐blinded, randomized controlled trial in general internal medicine units of a tertiary teaching hospital. Older inpatients with Confusion Assessment Method positive, hyperactive or mixed delirium within 48 h of admission or onset of in‐hospital delirium were included. The primary outcome was change in delirium severity measured with the Memorial Delirium Assessment Scale (MDAS). A previous pilot trial showed 120 participants randomized 1:1 to Melatonin or Placebo would provide 90% power to demonstrate a 3‐point reduction in the MDAS. Results: One hundred and twenty participants were randomized, 61 to Melatonin 5 mg and 59 to Placebo. The medication was well tolerated. The mean MDAS improvement was 4.9 (SD 7.6) in the Melatonin group and 5.4 (SD 7.2) in the Placebo group, p‐value 0.42, a non‐significant difference. A post‐hoc analysis showed length of stay (LOS) was shorter in the intervention group (median 9 days [Interquartile Range (IQR) 4, 12] vs. Placebo group 10 [IQR 6, 16] p‐value = 0.033, Wilcoxon Rank Sum test). Conclusions: This trial does not support the hypothesis that Melatonin reduces the severity of delirium. This may be due to no effect of Melatonin, a smaller effect than anticipated, an effect not captured on a multidimensional delirium assessment scale, or a type II statistical error. Melatonin may improve LOS; this hypothesis should be studied.
      pubtype: Academic Journal
      doctype: Article
      src: R
    language: English
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