Sleep-modulating pharmacological interventions for delirium prevention: a systematic review and a network meta-analysis of randomized controlled trials
In brief
Suvorexant halves delirium risk in hospitalized patients, meta-analysis shows
A network meta-analysis of 33 randomized trials (5,045 patients) found that suvorexant reduced delirium incidence by about 50% compared with usual care, while melatonin lowered risk by roughly 23%. Benefits were most apparent in non-ICU and surgical settings, but the evidence is only low to moderate quality, and direct head-to-head trials are still needed.
- Journal
- Sleep medicine reviews (Q1)
- Published
- 27 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Haizhen Chen, Yuyan Zhao, Yun Li, Wei Chen, Xiao Tan
- PMID
- 42673734
- DOI
- 10.1016/j.smrv.2026.102365
Why clinicians should know about it
- Picked for Critical Care and Intensive Care Medicine (top studies of the week, 6 September 2026): Network meta-analysis of RCTs, delirium prevention
Abstract
Delirium is a common neuropsychiatric syndrome among hospitalized patients and has been linked to disturbances in sleep and circadian regulation. We conducted a network meta-analysis of randomized controlled trials evaluating sleep-modulating pharmacological interventions for delirium prevention. PubMed, Embase, and Web of Science were searched through August 2025. Thirty-three trials involving 5045 patients were included. In the random-effects model, melatonin and melatonin receptor agonists were associated with a lower risk of delirium compared with non-active control conditions (RR = 0.77, 95% CI: 0.64-0.92). Evidence from suvorexant trials was also associated with a lower delirium risk (RR = 0.51, 95% CI: 0.27-0.95), whereas midazolam-based benzodiazepine evidence did not demonstrate a statistically significant reduction in delirium risk (RR = 1.64, 95% CI: 0.81-3.31). Subgroup analyses suggested that the association for melatonin-based interventions was more evident in non-ICU and surgical populations. The certainty of evidence ranged from low to moderate. Melatonin-based interventions and suvorexant were associated with lower delirium incidence; however, evidence directly comparing different active interventions remains limited, and findings should be interpreted cautiously given the agent-specific evidence base. Further direct comparative trials are needed to clarify the effectiveness and safety of sleep-modulating pharmacological interventions for delirium prevention.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.