Effect of melatonin on incidence of delirium among patients with hip fracture: a multicentre, double-blind randomized controlled trial

Jonghe, Annemarieke de; Munster, Barbara C. Van; Goslings, J. Carel; Kloen, Peter; Rees, C. van; Wolvius, R.; Velde, Romuald van; Levi, Marcel; Haan, Rob J. de; Rooij, Sophia E. de

doi:10.1503/cmaj.140495

Cited by 144 publications

(150 citation statements)

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“…Excluding the ramelteon trial [28], analysis of the outcomes from the three melatonin trials showed similar results (RR 0.53, 95 % CI 0.20 to 1.43; P=0.21), and heterogeneity of the data was still apparent (I 2 =85.0 %, P=0.001). Excluding the Jonghe 2014 trial [29], analysis showed a significant decrease in the incidence of delirium (RR 0.30, 95 % CI 0.17 to 0.53; P <0.0001) compared with control group. The trial by Jonghe 2014 [29] was the main cause to influence the stability of the incidence of delirium.…”

Section: Outcomes Analysismentioning

confidence: 91%

“…Ramelteon administered nightly to elderly patients with serious medical problems provided protection against delirium [28]. While Jonghe et al indicated that melatonin treatment has no significant effect on the incidence of delirium in elderly individuals with hip fracture but decreased the longlasting episode of delirium [29]. Thus, first, we performed a systemic review and meta-analysis to clarify the exact benefit of melatonin and ramelteon in delirium prevention.…”

Section: Introductionmentioning

confidence: 99%

“…Previous case reports indicated that administration of melatonin at 2 to 4 mg or ramelteon at 8 mg has some beneficial effects leading to prevention and management of delirium and has showed no adverse effects [22][23][24][25][26][27]. Through a systematic literature search, we obtained four clinical randomized controlled trials (RCTs) about exogenous melatonin for delirium prevention [28][29][30][31]. Unfortunately, the results of these published clinical trials were inconsistent.…”

Section: Introductionmentioning

confidence: 99%

“…Two of these doubleblinded RCTs showed a potential beneficial prevention of melatonin via decreasing the incidence of delirium with internal disease or surgical procedure [30,31]. However, the recent two high-quality clinical RCTs drew inconsistent conclusions [28,29]. Ramelteon administered nightly to elderly patients with serious medical problems provided protection against delirium [28].…”

Section: Introductionmentioning

confidence: 99%

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Exogenous Melatonin for Delirium Prevention: a Meta-analysis of Randomized Controlled Trials

et al. 2015

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Recently, two high-quality clinical randomized controlled trials (RCTs) regarding the preventive effect of exogenous melatonin on delirium drew inconsistent conclusions. We therefore performed a systemic review to explore whether melatonin had a benefit on delirium prevention. MEDLINE, EMBASE, and Cochrane Library were searched from January 1980 to April 2015 for English language studies. After strict selection and evaluation, the data were extracted from the included four RCTs. The primary outcome of this meta-analysis was the incidence of delirium. The secondary outcome was the improvement of sleep-wake rhythm. A total of four RCTs with 669 elderly patients were included in the present study. Melatonin group showed a tendency to decrease the incidence of delirium (relative risk [RR] 0.41, 95 % confidence interval [CI] 0.15 to 1.13; P = 0.08) compared with control group. In subgroup analysis of the elderly patients in medical wards, melatonin supplementation decreased the incidence of delirium by 75 % (RR 0.25, 95 % CI 0.07 to 0.88; P = 0.03), but not in sleep-wake disturbance (RR 1.24, 95 % CI 0.51 to 3.00; P = 0.64). No differences were found in the incidence of delirium between the two groups in the elderly patients that were presented to surgical wards. In conclusion, melatonin supplementation had a significant preventive effect in decreasing the incidence of delirium in elderly patients that were presented to medical wards. Further studies should provide sufficient evidence about the effect of melatonin on delirium in a large sample size.

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Section: Outcomes Analysismentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exogenous Melatonin for Delirium Prevention: a Meta-analysis of Randomized Controlled Trials

et al. 2015

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“…Almost all trials of cholinesterase inhibitors failed, 2 and effects of antipsychotics are controversial. [5][6][7][8][9][10][11] There is some emerging literature suggesting that melatonin prophylaxis may reduce delirium incidence or a long-lasting episode of delirium [12][13][14][15][16] and that PER Clock gene function may be disturbed in delirium. 17,18 Further, sleep-wake cycle disturbances including insomnia, excessive daytime napping, and disintegration of the expected circadian patterns have been described as a characteristic component of delirium for decades and demonstrated to be a core symptom domain of delirium.…”

mentioning

confidence: 99%

Preventive Effects of Suvorexant on Delirium

Hatta¹,

Kishi²,

Wada³

et al. 2017

J. Clin. Psychiatry

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Objective: No highly effective pharmacologic interventions to prevent delirium have been identified. We examined whether suvorexant, a potent and selective orexin receptor antagonist, is effective for the prevention of delirium. Methods: We conducted a multicenter, rater-blinded, randomized, placebo-controlled clinical trial in intensive care units and regular acute wards between April 2015 and March 2016. Eligible patients were 65 to 89 years old, newly admitted due to emergency, and able to take medicine orally and had an expected stay or life expectancy of 48 hours or more. Seventy-two patients were randomly assigned using the sealed envelope method to receive suvorexant (15 mg/d; 36 patients) or placebo (36 patients) every night for 3 days. The primary outcome measure was incidence of delirium as determined by the DSM-5. Trained psychiatrists assessed for delirium. Results: We found that delirium developed significantly less often among patients taking suvorexant than among those taking placebo (0% [n/N = 0/36] vs 17% [6/36], respectively, P = .025).Comparison by log-rank test also showed that delirium developed significantly less often among patients taking suvorexant than among those taking placebo (χ 2 = 6.46, P = .011). Analysis of variance revealed a tendency for main effect of treatment (F = 3.79, P = .053) on the sleep-wake cycle disturbance score (item 1) of the Japanese version of the Delirium Rating Scale-Revised-98 (DRS-R-98-J). There were no significant differences in adverse events.

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Delirium in Older Persons

Fong

Hshieh

et al. 2017

JAMA

656

306

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Importance-Delirium is defined as an acute disorder of attention and cognition. It is a common, serious, and often fatal condition among older patients. Although often underrecognized, delirium has serious adverse effects on the individual's function and quality of life, as well as broad societal effect with substantial health care costs.Objective-To summarize the current state of the art in diagnosis and treatment of delirium and to highlight critical areas for future research to advance the field.Evidence Review-We searched Ovid MEDLINE, Embase, and the Cochrane Library for the past 6 years, from January 1, 2011 until March 16, 2017 using a combination of controlled vocabulary and keyword terms. Since delirium is more prevalent in older adults, the focus was on studies in elderly populations; studies based solely in the intensive care unit (ICU) and non-English-language articles were excluded.Findings-Of 127 articles included, 25 were clinical trials, 42 cohort studies, 5 systematic reviews and meta-analyses, and 55 were other categories. A total of 11 616 patients were represented in the treatment studies. Advances in diagnosis have included the development of brief screening tools with high sensitivity and specificity, such as the 3-Minute Diagnostic Assessment, 4 A's test, and proxy-based measures such as the Family Confusion Assessment Method. Measures of severity, such as the Confusion Assessment Method-Severity Score, can aid in monitoring response to treatment, risk stratification, and assessing prognosis. Nonpharmacologic approaches focused on risk factors such as immobility, functional decline, visual or hearing impairment, dehydration, and sleep deprivation are effective for delirium prevention and also are recommended for delirium treatment. Current recommendations for pharmacologic treatment of

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Effect of melatonin on incidence of delirium among patients with hip fracture: a multicentre, double-blind randomized controlled trial

Cited by 144 publications

References 61 publications

Exogenous Melatonin for Delirium Prevention: a Meta-analysis of Randomized Controlled Trials

Exogenous Melatonin for Delirium Prevention: a Meta-analysis of Randomized Controlled Trials

Preventive Effects of Suvorexant on Delirium

Delirium in Older Persons

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