Melatonin and the Prevention and Management of Delirium: A Scoping Study

Choy, Sin Wei; Yeoh, Aun Chian; Lee, Zhao Zheng; Srikanth, Velandai; Moran, Chris

doi:10.3389/fmed.2017.00242

Cited by 17 publications

(11 citation statements)

References 65 publications

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“…However, trials investigating this have shown inconclusive results. [ 43 – 45 ] The complex diurnal regulation of melatonin and its effect on its multitude of receptors and inflammation feedback loops, may lead to unforeseen effects of exogenous administration. Specifically, inappropriately high melatonin levels may have deleterious effects such as hypoactive delirium.…”

Section: Discussionmentioning

confidence: 99%

Does the melatonin receptor 1B gene polymorphism have a role in postoperative delirium?

et al. 2018

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IntroductionPatients undergoing cardiac surgery are at high risk for postoperative delirium, which is associated with longer hospital and intensive care lengths of stays, increased morbidity and mortality. Because sleep disturbances are common in delirium, melatonin has been an area of interest in the treatment of delirium. The rs10830963 single nucleotide polymorphism of the melatonin receptor 1B gene can cause pathological dysfunction of this receptor and is associated with delayed morning offset of melatonin. We hypothesized patients undergoing aortic cardiac surgery who have the risk genotype of a melatonin receptor 1B polymorphism would have a higher incidence of postoperative delirium.MethodsNinety-eight patients undergoing aortic root or valve surgery underwent analysis for melatonin receptor 1B single nucleotide polymorphism, rs10830963. Using a validated method, CHART-DEL, all charts were retrospectively reviewed and scored for the presence of delirium while blinded to the results of the melatonin receptor 1B gene polymorphism.ResultsGenotyping for melatonin receptor 1B polymorphism was acceptable in 76 subjects of European descent of which 18 (23.7%) had delirium. Four of seven subjects with the risk genotype had delirium versus only 20.3% of subjects without the risk genotype. This carried an odds ratio of 5.2 (1.0, 26.1), p = 0.050.ConclusionThis observation suggests a role of the risk genotype of a melatonin receptor 1B polymorphism in the development of postoperative delirium. These hypotheses generating results warrant further prospective studies in a larger cohort group with delirium, circadian rhythm and melatonin assessments.

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Section: Discussionmentioning

confidence: 99%

Does the melatonin receptor 1B gene polymorphism have a role in postoperative delirium?

et al. 2018

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“…Melatonin has shown conflicting results as a preventative agent for POD in a few small RCTs. 144 Tryptophan was not effective in reducing either delirium incidence or duration in a randomised control trial. 145 The multiple negative trials for pharmacological prevention of delirium raise the possibility that we need to better understand the pathophysiology of delirium in order to prevent specific pathophysiological processes that play an aetiological role in delirium.…”

Section: Preventionmentioning

confidence: 93%

“…In retrospective cohort studies, melatonin and ramelteon have been associated with decreased use of antipsychotics, but no difference in severity. 144 A multicentre RCT investigating rivastigmine, a cholinesterase inhibitor, as an adjuvant to haloperidol was halted early, as mortality was increased in the rivastigmine group in addition to longer duration of delirium. 178 Studies specifically investigating how to mitigate dNCR and NCD (postoperative) are lacking.…”

Section: Treatmentmentioning

confidence: 99%

State of the clinical science of perioperative brain health: report from the American Society of Anesthesiologists Brain Health Initiative Summit 2018

Mahanna‐Gabrielli

Schenning

Eriksson

et al. 2019

British Journal of Anaesthesia

165

187

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Cognitive recovery after anaesthesia and surgery is a concern for older adults, their families, and caregivers. Reports of patients who were 'never the same' prompted a scientific inquiry into the nature of what patients have experienced. In June 2018, the ASA Brain Health Initiative held a summit to discuss the state of the science on perioperative cognition, and to create an implementation plan for patients and providers leveraging the current evidence. This group included representatives from the AARP (Area. This paper summarises the state of the relevant clinical science, including risk factors, identification and diagnosis, prognosis, disparities, outcomes, and treatment of perioperative neurocognitive disorders. Finally, we discuss gaps in current knowledge with suggestions for future directions and opportunities for clinical and translational projects.

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“…Although there is growing interest in the role of melatonin and melatonin receptor agonists in promoting sleep and preventing delirium in critical care and other high-risk populations, [ 34 ] heterogeneity among delirium prevention studies with melatonin supplementation precludes broad conclusive recommendations [ 35 ]. Although two systematic reviews and meta-analyses failed to show statistically significant benefit in delirium prevention for melatonin or its agonist, ramelteon across postoperative, intensive care and older medical populations, [ 36 , 37 ] a sub-group analysis estimated that melatonin administration decreased the incidence of delirium by 75% in older (> 65 years) medical patients [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

Melatonin to prevent delirium in patients with advanced cancer: a double blind, parallel, randomized, controlled, feasibility trial

et al. 2020

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Background Delirium is highly problematic in palliative care (PC). Preliminary data indicate a potential role for melatonin to prevent delirium, but no randomized controlled trials (RCTs) are reported in PC. Methods Patients aged ≥18 years, with advanced cancer, admitted to an inpatient Palliative Care Unit (PCU), having a Palliative Performance Scale rating ≥ 30%, and for whom consent was obtained, were included in the study. Patients with delirium on admission were excluded. The main study objectives were to assess the feasibility issues of conducting a double-blind RCT of exogenous melatonin to prevent delirium in PC: recruitment, retention, procedural acceptability, appropriateness of outcome measures, and preliminary efficacy and safety data. Study participants were randomized in a double-blind, parallel designed study to receive daily melatonin 3 mg or placebo orally at 21:00 over 28 days or less if incident delirium, death, discharge or withdrawal occurred earlier. Delirium was diagnosed using the Confusion Assessment Method. Efficacy endpoints in the melatonin and placebo groups were compared using time-to-event analysis: days from study entry to onset of incident delirium. Results Over 16 months, 60/616 (9.7%; 95% CI: 7.5–12.4%) screened subjects were enrolled. The respective melatonin (n = 30) vs placebo (n = 30) outcomes were: incident delirium in 11/30 (36.7%; 95%CI: 19.9–56.1%) vs 10/30 (33%; 95% CI: 17.3–52.8%); early discharge (6 vs 5); withdrawal (6 vs 3); death (0 vs 1); and 7 (23%) vs 11 (37%) reached the 28-day end point. The 25th percentile time-to-event were 9 and 18 days (log rank, χ2 = 0.62, p = 0.43) in melatonin and placebo groups, respectively. No serious trial medication-related adverse effects occurred and the core study procedures were acceptable. Compared to those who remained delirium-free during their study participation, those who developed delirium (n = 21) had poorer functional (p = 0.036) and cognitive performance (p = 0.013), and in particular, poorer attentional capacity (p = 0.003) at study entry. Conclusions A larger double-blind RCT is feasible, but both subject accrual and withdrawal rates signal a need for multisite collaboration. The apparent trend for shorter time to incident delirium in the melatonin group bodes for careful monitoring in a larger trial. Trial registration Registered on July 21st 2014 with ClinicalTrials.gov: NCT02200172.

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Melatonin and the Prevention and Management of Delirium: A Scoping Study

Cited by 17 publications

References 65 publications

Does the melatonin receptor 1B gene polymorphism have a role in postoperative delirium?

Does the melatonin receptor 1B gene polymorphism have a role in postoperative delirium?

State of the clinical science of perioperative brain health: report from the American Society of Anesthesiologists Brain Health Initiative Summit 2018

Melatonin to prevent delirium in patients with advanced cancer: a double blind, parallel, randomized, controlled, feasibility trial

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