Melatonergic agents in the prevention of delirium: A network meta-analysis of randomized controlled trials

Area of Science:

• Geriatric Medicine
• Pharmacology
• Critical Care

Background:

• Disruption of the sleep-wake cycle is a known risk factor and prodromal indicator for delirium.
• Melatonergic agents, which regulate sleep, are being investigated for their potential role in delirium prevention.

Purpose of the Study:

• To systematically review and perform a network meta-analysis (NMA) on the efficacy and tolerability of melatonergic agents for delirium prevention.
• To identify the most effective melatonergic agent and dosage for preventing delirium in at-risk patients.

Main Methods:

• A literature search was conducted across eight databases.
• Six randomized controlled trials (RCTs) involving 913 adult participants (mean age 78.8 years, 59.4% female) were included.
• A frequentist model network meta-analysis (NMA) was used to compare the preventive effects of melatonergic agents against placebo.

Main Results:

• Melatonin (5 mg/day), melatonin (0.5 mg/day), and ramelteon (8 mg/day) demonstrated significant preventive effects against placebo.
• Odds Ratios (OR) for prevention were: melatonin (5 mg/day) [OR=0.21], melatonin (0.5 mg/day) [OR=0.16], and ramelteon (8 mg/day) [OR=0.28].
• The Surface Under the Cumulative Ranking Curve (SUCRA) indicated that 0.5 mg/day of melatonin had the highest preventive efficacy.

Conclusions:

• Low-dose melatonergic agents show significant efficacy in preventing delirium.
• Melatonin at 0.5 mg/day appears to be the most effective agent for delirium prevention.
• These findings support the recommendation of low-dose melatonergic agents in clinical practice guidelines for delirium prevention.