HormonesMelatonin

Melatonin and melatonin receptor agonists reduce delirium risk in hospitalized patients

In a network meta-analysis of 33 randomized controlled trials involving 5045 patients, melatonin and melatonin receptor agonists were associated with a 23% lower risk of delirium compared with non-active control conditions (RR=0.77, 95% CI: 0.64-0.92). The effect was more evident in non-ICU and surgical populations, but the certainty of evidence was low to moderate.

Last updated: Sep 2, 2026•0 RCTs•1 Meta-analyses•📖 Read as article →

Evidence Score

Evidence Score49/100
Human RCT☆☆☆☆☆
Meta-analysis★★★☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. Sleep-modulating pharmacological interventions for delirium prevention: a systematic review and a network meta-analysis of randomized controlled trials.

observational

Chen H, Zhao Y, Li Y, Chen W, Tan X · Sleep medicine reviews (2026)

Participants: N/A
Duration: N/A
Intervention: Melatonin or melatonin receptor agonists (e.g., ramelteon) administered for delirium prevention
Outcome: Incidence of delirium
Effect Size: RR=0.77 (95% CI: 0.64-0.92)
Population: Hospitalized patients (including non-ICU and surgical populations) at risk for delirium

Result:

PubMed: 42673734DOI: 10.1016/j.smrv.2026.102365

Mechanism Graph

Melatonin agonists bind to melatonin receptors in the suprachiasmatic nucleus
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This regulates circadian rhythms and promotes sleep
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Improved sleep and circadian alignment may reduce neuroinflammation and delirium triggers
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Result: Lower incidence of delirium

Limitations

  • ⚠Certainty of evidence ranged from low to moderate
  • ⚠Limited direct comparisons between active interventions
  • ⚠Agent-specific evidence base; findings may not generalize to all melatonin receptor agonists

Frequently Asked Questions

What is the effect of melatonin on delirium prevention?▼

Melatonin and melatonin receptor agonists reduce delirium risk by 23% compared to control (RR=0.77, 95% CI: 0.64-0.92).

In which patient populations is melatonin most effective for delirium prevention?▼

Subgroup analyses suggest the effect is more evident in non-ICU and surgical populations.

How does melatonin compare to suvorexant for delirium prevention?▼

Both melatonin (RR=0.77) and suvorexant (RR=0.51) reduce delirium risk, but direct comparisons are limited.

Are benzodiazepines like midazolam effective for delirium prevention?▼

No, midazolam-based benzodiazepines did not show a statistically significant reduction in delirium risk (RR=1.64, 95% CI: 0.81-3.31).

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References

  1. 1.Chen H, Zhao Y, Li Y, Chen W, Tan X. "Sleep-modulating pharmacological interventions for delirium prevention: a systematic review and a network meta-analysis of randomized controlled trials.." Sleep medicine reviews, 2026. PMID: 42673734 DOI: 10.1016/j.smrv.2026.102365
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.