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Promoting Healthy Sleep–Wake and Circadian Rhythms to Prevent Delirium: Next Step, Target Engagement
Mark A. Oldham. Journal of the American Geriatrics Society, 2026-03-05
Topic: Risk, prevention and care in population studies
First, based on pooled results of RCTs, the melatonin agonists melatonin and ramelteon were not found to reduce delirium incidence (RR 0.94, 95% CI 0.72–1.22, k = 16 studies; RR 0.63, 95% CI 0.39–1.03, k = 8, respectively). However, pooled results from 3 RCTs found that the DORA suvorexant significantly reduced the incidence of delirium versus placebo (RR 0.55, 95% CI 0.35–0.87). In observational studies, which are susceptible to several sources of bias such as confounding by indication and selection bias, the authors again found that melatonin was not associated with lower delirium incidence (k = 3). However, in observational studies, both ramelteon and DORAs were associated with a statistically lower incidence of delirium relative to comparison groups (four studies each). The only significant finding in subgroup analyses was that, in observational studies, a greater effect was found in study arm subjects in surgical-only cohorts than in medical or mixed cohorts. When interpreting the results of this review, it is important to differentiate sleep–wake and circadian rhythms, as these two are related but distinct and dissociable biological constructs. This review's null results for melatonin, both in RCTs and observational studies, question the role of melatonin in preventing delirium. The discrepant results between RCTs and observational studies for ramelteon are less clear. It could be that there is a true but weak signal in favor of ramelteon, or the results from observational studies could be a false positive due to confounding by the limitations of observational study designs. In either event, the results do not support the routine use of either melatonin or ramelteon for delirium prevention. Conversely, the American Psychiatric Association's Practice Guideline for the Prevention and Treatment of Delirium [9] suggests that melatonin and ramelteon not be used to prevent or treat delirium. The current results [2] are more in line with the latter of these two positions. Although this suggests that ramelteon did not exert a circadian effect in this study, rest-activity patterns are only a proxy for circadian phase. The pooled results for DORAs are promising, but the authors are appropriate to regard these findings as hypothesis-generating given the small size of most included studies. Second, the DORA studies have not investigated objective sleep outcomes as a demonstration of target engagement, though the results of the recent REPOSE study, which does eva
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Oldham, M. A. (2026). Promoting Healthy Sleep–Wake and Circadian Rhythms to Prevent Delirium: Next Step, Target Engagement. Journal of the American Geriatrics Society. https://doi.org/10.1111/jgs.70369
Vancouver
Oldham MA. Promoting Healthy Sleep–Wake and Circadian Rhythms to Prevent Delirium: Next Step, Target Engagement. Journal of the American Geriatrics Society. 2026. doi:10.1111/jgs.70369. PMID: 41784080.
BibTeX
@article{oldham2026-41784080,
author = {Oldham, Mark A.},
title = {{Promoting Healthy Sleep–Wake and Circadian Rhythms to Prevent Delirium: Next Step, Target Engagement}},
journal = {Journal of the American Geriatrics Society},
year = {2026},
doi = {10.1111/jgs.70369},
pmid = {41784080},
url = {https://doi.org/10.1111/jgs.70369}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- First, based on pooled results of RCTs, the melatonin agonists melatonin and ramelteon were not found to reduce delirium incidence (RR 0.94, 95% CI 0.72–1.22, k = 16 studies; RR 0.63, 95% CI 0.39–1.03, k = 8, respectively).
- However, pooled results from 3 RCTs found that the DORA suvorexant significantly reduced the incidence of delirium versus placebo (RR 0.55, 95% CI 0.35–0.87).
- In observational studies, which are susceptible to several sources of bias such as confounding by indication and selection bias, the authors again found that melatonin was not associated with lower delirium incidence (k = 3).
- However, in observational studies, both ramelteon and DORAs were associated with a statistically lower incidence of delirium relative to comparison groups (four studies each).
- The only significant finding in subgroup analyses was that, in observational studies, a greater effect was found in study arm subjects in surgical-only cohorts than in medical or mixed cohorts.
Why it matters
Pooled results from randomized trials found that melatonin and ramelteon did not reduce delirium incidence, while suvorexant did reduce it versus placebo. Because delirium is a modifiable risk factor for dementia, these findings may inform prevention efforts, but the review notes that observational studies are susceptible to bias.
Study details
- Study designsystematic review
- Participants203
- Effect sizeRR 0.94; RR 0.63; RR 0.55
- Evidence strengthHigh
How this study scored 60/100
Published in a peer-reviewed journal, and it is a systematic review of all the studies on the question.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of the American Geriatrics Society) |
| Journal's citation record | 3 / 4 | Journal of the American Geriatrics Society: journal h-index 344 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A systematic review of all the studies on the question |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 203 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | A review of other studies — randomization is not credited here |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 3 / 6 | Cited 5.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Mark A. Oldham: h-index 51 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Rochester Medicine: institution h-index 953 (OpenAlex) |
| Multicenter collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41784080) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 60 / 100 | — |
What each of these 20 components measures, and what this score is not →
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