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Melatonin Receptor Agonists for the Prevention of Delirium: An Updated Systematic Review and Meta-Analysis of
Benchalak Maneeton1, Subsai Kongsaengdao2,3, Narong Maneeton1
1Department of Psychiatry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Background:
Although a previous review illustrated the efficacy of melatonin receptor agonists (MRAs) in preventing delirium, some recent randomized controlled trials (RCTs) did not confirm these effects.
Objectives:
This study systematically reviewed the efficacy, acceptability, and tolerability of MRAs for delirium prevention.
Materials And Methods:
We searched electronic databases, including Scopus, PubMed, CINAHL, and Controlled Trials Register, from their inception to February 20, 2022. The primary efficacy outcome was delirium incidence rate after MRA administration; relative risks (RRs), overall discontinuation, and discontinuation due to adverse events are also presented.
Results:
The overall pooled incidence rates of delirium in MRA-treated and placebo-treated groups were significantly different with RR (95% CI)=0.66(0.52, 0.84, ), I2=59%. Similarly, the incidence rate was significantly lower in the melatonin-treated group than in the placebo-treated group [RR (95% CI) =0.65 (0.49, 0.88), I2=65%]. Unfortunately, incidence rates were not significantly different between ramelteon-treated and placebo-treated groups [RR (95% CI) =0.67 (0.42, 1.08), I2=50%]. The pooled incidence rate of delirium in either melatonin or ramelteon-treated groups was not significantly different from the placebo-treated group in elderly patients. The pooled incidence rate of delirium was significantly lower in the melatonin-treated group than in the benzodiazepinetreated group.
Conclusion:
Based on this review, melatonin could prevent delirium with a small effect size. However, ramelteon did not show efficacy in preventing delirium. Additionally, neither melatonin nor ramelteon individually showed effectiveness in preventing delirium in elderly patients. Therefore, using MRAs to prevent delirium in clinical practice should be cautious. However, future welldefined and large sample size studies could verify these findings.
Insights
Melatonin may help prevent delirium, but ramelteon does not show efficacy. Caution is advised when using melatonin receptor agonists (MRAs) for delirium prevention, especially in elderly patients, pending further research.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Geriatrics
Background:
- Previous reviews indicated melatonin receptor agonists (MRAs) efficacy in delirium prevention.
- Recent randomized controlled trials (RCTs) have yielded conflicting results regarding MRA effectiveness.
Purpose of the Study:
- To systematically review the efficacy, acceptability, and tolerability of MRAs for delirium prevention.
- To analyze the incidence rates of delirium following MRA administration.
Main Methods:
- Systematic literature search of multiple electronic databases (Scopus, PubMed, CINAHL, etc.) up to February 20, 2022.
- Meta-analysis of primary efficacy outcome (delirium incidence rate) and secondary outcomes (discontinuation rates).
Main Results:
- Melatonin significantly reduced delirium incidence compared to placebo (RR=0.65).
- Ramelteon did not show a significant difference in delirium incidence compared to placebo.
- Neither melatonin nor ramelteon demonstrated significant efficacy in preventing delirium in elderly patients.
Conclusions:
- Melatonin shows a small effect in preventing delirium, while ramelteon lacks demonstrated efficacy.
- Current evidence suggests cautious use of MRAs for delirium prevention in clinical practice.
- Further large-scale, well-defined studies are needed to confirm these findings.
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