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

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.