Molecular Neurobiology

, Volume 53, Issue 6, pp 4046–4053 | Cite as

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

  • Sheng Chen
  • LiGen Shi
  • Feng Liang
  • Liang Xu
  • Doycheva Desislava
  • Qun Wu
  • Jianmin Zhang


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.


Delirium Melatonin Sleep–wake cycle Meta-analysis 



This study was supported by National Natural Science Foundation of China (No. 81171096 and No. 81371433) to JM Zhang and National Natural Science Foundation of China (No. 81271273) to Q Wu.

Conflict of interest

The authors report no financial or other relationship relevant to the subject of this article.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Sheng Chen
    • 1
  • LiGen Shi
    • 1
  • Feng Liang
    • 1
  • Liang Xu
    • 1
  • Doycheva Desislava
    • 2
  • Qun Wu
    • 1
  • Jianmin Zhang
    • 1
  1. 1.Department of Neurosurgery, Second Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
  2. 2.Department of Physiology and PharmacologyLoma Linda UniversityLoma LindaUSA

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