Melatonin Research

Melatonin Use in the ICU: A Systematic Review and Meta-Analysis

Tang BHY et al. • Critical care medicine (2025)

Our findings suggest that melatonin administration in the critically ill may improve perceived sleep and reduce delirium, without increasing adverse effects.

• Our findings suggest that melatonin administration in the critically ill may improve perceived sleep and reduce delirium, without increasing adverse effects.
• Certainty of evidence was negatively affected by the risk of bias and inconsistency.
• Future RCTs should focus on identifying optimal dosing, administration timing, improving measurements of sleep outcomes, and target populations.

Comparative Efficacy, Tolerability, and Acceptability of Donanemab, Lecanemab, Aducanumab, Melatonin, and Aerobic Exercise for a Short Time on Cognitive Function in Mild Cognitive Impairment and Mild Alzheimer's Disease: A Systematic Review and Network Meta-Analysis

Terao I et al. • Journal of Alzheimer's disease : JAD (2024)

Melatonin may be a better potential disease-modifying treatment for cognitive decline in mild AD and MCI.

• Melatonin may be a better potential disease-modifying treatment for cognitive decline in mild AD and MCI.
• Aerobic exercise for a short time might also be better than donanemab, lecanemab and aducanumab if continued, as it is well tolerated and more effective, although less valid due to heterogeneity.
• Another limitation is the small number of participants.

Efficacy and safety of perioperative melatonin for postoperative delirium in patients undergoing surgery: a systematic review and meta-analysis

Shin HW et al. • The Journal of international medical research (2024)

Perioperative melatonin or melatonin agonist treatment suppressed POD without severe adverse events, particularly at higher doses, during the early postoperative period, and after cardiopulmonary surgery.

• Perioperative melatonin or melatonin agonist treatment suppressed POD without severe adverse events, particularly at higher doses, during the early postoperative period, and after cardiopulmonary surgery.
• Published in The Journal of international medical research (2024)
• Further research warranted to confirm findings

Efficacy of melatonin and ramelteon for the acute and long-term management of insomnia disorder in adults: A systematic review and meta-analysis

Maruani J et al. • Journal of sleep research (2023)

PR melatonin for individuals with a mean age ≥ 55 and ramelteon show larger effect sizes.© 2023 European Sleep Research Society.

• For the subgroup mean age of patients ≥55, PR melatonin was efficacious on oSE with a large effect size (p < 0.001; weighted difference = 2.95%).
• Regarding long-term effects, ramelteon has a large effect size on oTST (p < 0.001; weighted difference = 2.02 min) and sTST (p < 0.001; weighted difference = 14.5 min).
• PR melatonin and ramelteon appear efficacious compared with placebo for insomnia symptoms with PR melatonin showing mostly small to medium effect sizes.

Efficacy and moderators of prevention and treatment of delirium with melatonin receptor agonists: A systematic review and meta-analysis of randomized controlled trials

Wada M et al. • General hospital psychiatry (2023)

This study provides evidence of the potential effects of MRAs in preventing delirium and reducing mortality.

• Additionally, MRAs were associated with a significant reduction in mortality rate (risk ratio = 0.90, p = 0.02) in delirium prevention studies.
• This study provides evidence of the potential effects of MRAs in preventing delirium and reducing mortality.
• Further research is required to elucidate the therapeutic potential of MRAs for delirium and identify specific patient populations that may benefit from this agent.

Melatonin intervention to prevent delirium in the intensive care units: a systematic review and meta-analysis of randomized controlled trials

Duan Y et al. • Frontiers in endocrinology (2023)

Melatonin reduced the incidence of delirium in CCU patients, but did not significantly reduce the incidence of delirium in GICU patients.

• The results of the meta-analysis showed that melatonin did not reduce the incidence of delirium in ICU patients (odds ratio [OR]: 0.71; 95% confidence interval [CI]: 0.46 to 1.12; p = 0.14).
• There was a strong hetero-geneity between the selected studies (I2 = 74%).
• Subgroup analysis results showed that melatonin reduced the incidence of delirium in cardiovascular care unit (CCU) patients (OR: 0.52; 95% CI: 0.37 to 0.73; p=0.0001), but did not in general intensive care unit (GICU) patients (OR: 1.14; 95% CI: 0.86 to 1.50; p=0.35).

Melatonin for sleep disorders in people with autism: Systematic review and meta-analysis

Nogueira HA et al. • Progress in neuro-psychopharmacology & biological psychiatry (2023)

All rights reserved.

• According to the global analysis, the wake after sleep onset and night awakening parameters were not statistically significant.
• Melatonin has possible efficacy over total time, latency, and efficiency sleep parameters.Copyright © 2023 Elsevier Inc.
• All rights reserved.

Efficacy on sleep parameters and tolerability of melatonin in individuals with sleep or mental disorders

Falk E et al. • Neuroscience & Biobehavioral Reviews (2022)

Melatonin significantly improved sleep onset latency and total sleep time in both children/adolescents and adults.

• Effective in neurodevelopmental disorders
• Improves delayed sleep phase disorder
• Good tolerability profile

Safety of higher doses of melatonin in adults: A systematic review and meta-analysis

Menczel Schrire Z et al. • Journal of pineal research (2022)

Published by John Wiley & Sons Ltd.

• A total of 29 studies (37%) made no mention of the presence or absence of AEs.
• Overall, there has been limited AE reporting from high-dose melatonin studies.
• Based on this limited evidence, melatonin appears to have a good safety profile.

Hypnotic and Melatonin/Melatonin-Receptor Agonist Treatment in Bipolar Disorder: A Systematic Review and Meta-Analysis

McGowan NM et al. • CNS drugs (2022)

There is a paucity of studies examining pharmacological interventions for sleep and circadian rhythm disturbance in BD.

• The largest efficacy signal detected was for manic symptoms (four studies; g = - 0.44 [95% CI - 1.03 to 0.14]) but there was substantial heterogeneity between studies and patient characteristics.
• There is a paucity of studies examining pharmacological interventions for sleep and circadian rhythm disturbance in BD.
• Few studies assessed sleep-related symptoms, and none quantitatively examined endogenous melatonin patterns or other circadian rhythms.

Melatonin for delirium prevention in hospitalized patients: A systematic review and meta-analysis

Khaing K et al. • Journal of psychiatric research (2021)

Melatonin/ramelteon are associated with reduction in delirium incidence in hospitalized patients.

• Melatonin/ramelteon are associated with reduction in delirium incidence in hospitalized patients.
• However, this effect seems confined to surgical and ICU patients.
• The optimum dosage and formulation of melatonin, and treatment duration remain uncleared and open to further studies with larger sample sizes.

The effects of melatonin therapy on the treatment of patients with Non-alcoholic steatohepatitis: A systematic review and Meta-analysis on clinical trial studies

Akhavan Rezayat A et al. • European journal of pharmacology (2021)

All rights reserved.

• There was a significant reduction in cholesterol levels (P = 0.005).
• Melatonin could reduce the progress of NAFLD.
• It might also decrement hepatic function parameters.

Melatonin for preoperative and postoperative anxiety in adults

Madsen BK et al. • The Cochrane database of systematic reviews (2020)

When compared with placebo, melatonin given as premedication (as tablets or sublingually) probably reduces preoperative anxiety in adults (measured 50 to 120 minutes after administration), which is potentially clinically relevant.

• When compared with placebo, melatonin given as premedication (as tablets or sublingually) probably reduces preoperative anxiety in adults (measured 50 to 120 minutes after administration), which is potentially clinically relevant.
• The effect of melatonin on postoperative anxiety compared to placebo (measured in the recovery room and six hours after surgery) was also evident but was much smaller, and the clinical relevance of this finding is uncertain.
• There was little or no difference in anxiety when melatonin was compared with benzodiazepines.

Melatonin in cancer treatment

Yu ZY et al. • The Cochrane database of systematic reviews (2025)

The available evidence is of very low certainty, so we are unable to draw conclusions about the effects of melatonin on quality of life and sleep at three months in people receiving treatment for cancer.

• We downgraded the certainty of the evidence because of high risk of bias, small sample size, the width of the 95% confidence interval, and indirectness due to inadequate reporting of cancer type.
• Melatonin likely reduces the incidence of fatigue (RR 0.46, 95% CI 0.39 to 0.55; 10 studies, 1359 participants; moderate-certainty evidence) and may reduce nausea (RR 0.85, 95% CI 0.72 to 1.00; 6 studies, 710 participants; low-certainty evidence).
• We downgraded the certainty of the evidence because of the high risk of bias and the width of the 95% confidence interval.

Meta-analysis of melatonin for sleep disorders

Ferracioli-Oda E et al. • PLOS ONE (2013)

Melatonin significantly reduced sleep onset latency, increased total sleep time, and improved overall sleep quality.

• Reduces time to fall asleep by 7 minutes on average
• Increases total sleep time
• Improves sleep quality scores

EFFICACY OF MELATONIN AS AN ADJUNCT TO NONSURGICAL PERIODONTAL THERAPY: A SYSTEMATIC REVIEW AND META-ANALYSIS.

Abusamak M, Al-Tamimi M, Elananza A, Alshdaifat I, Quadier N, Abdalkader Y • J Evid Based Dent Pract (2026)

Melatonin as a Novel Drug to Improve Cardiac Function and Quality of Life in Heart Failure Patients: A Systematic Review and Meta-Analysis

Daliri AS et al. • Clinical cardiology (2025)

Thus, melatonin, by increasing psychologic parameters and cardiac potency, could be advised as a novel drug for treatment and palliating heart failure patients.

• As the effect of melatonin, fatigue, and NT-Pro BNP were reduced but on the contrary sleep quality, appetite, and FMD (Flow-Mediated Dilation) significantly increased.
• Thus, melatonin, by increasing psychologic parameters and cardiac potency, could be advised as a novel drug for treatment and palliating heart failure patients.
• Further research warranted to confirm findings

Pharmacotherapies for sleep disturbances in dementia

McCleery J et al. • The Cochrane database of systematic reviews (2020)

We discovered a distinct lack of evidence to guide decisions about drug treatment of sleep problems in dementia.

• We could synthesise data for two of our primary sleep outcomes: total nocturnal sleep time (TNST) (MD 10.68 minutes, 95% CI -16.22 to 37.59; 2 studies, n = 184), and the ratio of day-time to night-time sleep (MD -0.13, 95% CI -0.29 to 0.03; 2 studies; n = 184).
• We found low-certainty evidence that trazodone 50 mg for two weeks may improve TNST (MD 42.46 minutes, 95% CI 0.9 to 84.0; 1 study, n = 30), and sleep efficiency (MD 8.53%, 95% CI 1.9 to 15.1; 1 study, n = 30) in people with moderate-to-severe AD.
• The effect on time awake after sleep onset was uncertain due to very serious imprecision (MD -20.41 minutes, 95% CI -60.4 to 19.6; 1 study, n = 30).

Optimizing the Time and Dose of Melatonin as a Sleep-Promoting Drug: A Systematic Review of Randomized Controlled Trials and Dose-Response Meta-Analysis

Cruz-Sanabria F et al. • Journal of pineal research (2024)

Published by John Wiley & Sons Ltd.

• Dose-response meta-analysis showed that melatonin gradually reduces sleep onset latency and increases total sleep time, peaking at 4 mg/day.
• Published by John Wiley & Sons Ltd.
• Further research warranted to confirm findings

Effect of melatonin supplementation on cardiometabolic risk factors, oxidative stress and hormonal profile in PCOS patients: a systematic review and meta-analysis of randomized clinical trials

Ziaei S et al. • Journal of ovarian research (2024)

Melatonin is a potential antioxidant that may prevent damage from oxidative stress in patients with PCOS.

• Melatonin is a potential antioxidant that may prevent damage from oxidative stress in patients with PCOS.
• However, the clear effect of melatonin supplementation on cardiometabolic risk factors, hormonal outcomes, and pregnancy-related outcomes needs to be evaluated further in large populations and long-term RCTs.
• Further research warranted to confirm findings