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, 19 (1), 272

Melatonin for the Prevention of Postoperative Delirium in Older Adults: A Systematic Review and Meta-Analysis


Melatonin for the Prevention of Postoperative Delirium in Older Adults: A Systematic Review and Meta-Analysis

Ashley M Campbell et al. BMC Geriatr.


Background: Older surgical patients are at high risk of developing postoperative delirium. Non-pharmacological strategies are recommended for delirium prevention, but no pharmacological agents have compelling evidence to decrease the incidence of delirium. The purpose of this study was to assess whether perioperative melatonin decreases the incidence of delirium in older adults undergoing surgical procedures.

Methods: A systematic search using PubMed/Medline, Embase, PsycINFO, CINAHL, and references of identified articles published in English between January 1990 and October 2017 was performed. Two independent reviewers screened titles and abstracts, and then extracted data following a full-text review of included articles with consensus generation and bias assessment. Studies reporting outcomes for melatonin or ramelteon use to prevent delirium in postoperative hospitalized patients (mean age ≥ 50 years) were eligible for inclusion. Data were pooled using a fixed-effects model to generate a forest plot and obtain a summary odds ratio for the outcome of interest (delirium incidence). Cochran's Q and I2 values were used to investigate heterogeneity.

Results: Of 335 records screened, 6 studies were selected for the qualitative analysis and 6 were included in the meta-analysis (n = 1155). The mean age of patients in included studies ranged from 59 to 84 years. Patients in intervention groups typically received melatonin or ramelteon at daily doses of two to eight milligrams around cardiothoracic, orthopedic, or hepatic surgeries for one to nine days, starting on the evening before or the day of surgery. The incidence of delirium ranged from 0 to 30% in the intervention groups versus 4-33% in the comparator groups, and was significantly reduced in the melatonin group, with a summary effect of the meta-analysis yielding an odds ratio of 0.63 (95% CI 0.46 to 0.87; 0.006; I2 = 72.1%). A one study removed analysis reduced overall odds ratio to 0.310 (95% CI 0.19 to 0.50), while reducing heterogeneity (Cochran's Q = 0.798, I2 = 0.000).

Conclusion: Perioperative melatonin reduced the incidence of delirium in older adults in the included studies. While optimal dosing remains an unanswered question, the potential benefit of melatonin and melatonin receptor agonists may make them a reasonable option to use for delirium prevention in older adults undergoing surgical procedures.

Keywords: Delirium; Geriatric; Melatonin; Postoperative; Ramelteon.

Conflict of interest statement

The authors declare that they have no competing interests.


Fig. 1
Fig. 1
PubMed search strategy
Fig. 2
Fig. 2
Study inclusion criteria
Fig. 3
Fig. 3
PRISMA 2009 Flow Diagram [35]
Fig. 4
Fig. 4
Forest plot of melatonin studies for the prevention of delirium in postoperative patients
Fig. 5
Fig. 5
Meta-analysis funnel plot

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    1. American Psychiatric Association, Diagnostic and Statistical Manual, 5th ed, APA Press, Washington, DC; 2013.
    1. Pitkala KH, Laurila JV, Strandberg TE, Tilvis RS. Prognostic significance of delirium in frail older people. Dement Geriatr Cogn Disord. 2005;19:158–163. doi: 10.1159/000082888. - DOI - PubMed
    1. Buurman BM, Hoogerduijn JG, de Haan RJ, et al. Geriatric conditions in acutely hospitalized older patients: prevalence and one-year survival and functional decline. PLoS One. 2011;6:e26951. doi: 10.1371/journal.pone.0026951. - DOI - PMC - PubMed
    1. Leslie DL, Zhang Y, Holford TR, Bogardus ST, Leo-Summers LS, Inouye SK. Premature death associated with delirium at 1-year follow-up. Arch Intern Med. 2005;165:1657–1662. doi: 10.1001/archinte.165.14.1657. - DOI - PubMed
    1. Saczynski JS, Marcantonio ER, Quach L, et al. Cognitive trajectories after postoperative delirium. N Engl J Med. 2012;367:30–39. doi: 10.1056/NEJMoa1112923. - DOI - PMC - PubMed

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