| Sumario: | Background Delirium is a serious neuropsychiatric condition common among older adults, associated with prolonged hospital stays, increased morbidity and mortality. Although guidelines emphasise prevention, identifying most effective measures is crucial. Objective To evaluate the efficacy of non-pharmacological and pharmacological interventions in preventing delirium in older adults (≥65 years). Methods We conducted a systematic review and meta-analysis of randomised controlled trials across settings, excluding ICU-only studies. MEDLINE, Cochrane, Web of Science and PsycINFO were searched through October 2024. Comparators included standard care, placebo, or other drugs. Random-effects models estimated pooled risk ratios. Risk of bias was assessed using RoB 2.0. Subgroup analyses were performed by setting and drug type. PROSPERO: CRD42024500387. Results Eighty-seven trials (19,289 randomised patients) were included. Non-pharmacological multicomponent interventions (k = 17) significantly reduced delirium occurrence (risk ratio [RR] = 0.56, 95% CI 0.45–0.72; I = 63%) versus usual care, although certainty of evidence was very low. Effects were significant in non-cardiovascular surgical and medical patients. Single-component non-pharmacological interventions (k = 9) showed mixed or inconclusive findings. Among pharmacological trials (k = 53), dexmedetomidine reduced delirium risk (RR = 0.49; 95% CI 0.43–0.57; low-certainty) in non-cardiovascular surgical patients. Corticosteroids and intranasal insulin showed significant effects (high-certainty), based on a small number of trials. Mixed strategies, such as haemodynamic or cerebral oxygen-guided approaches, suggested potential benefit but were heterogeneous. Conclusions Non-pharmacological multicomponent interventions reduce delirium occurrence and should be prioritised. Dexmedetomidine showed benefit in non-cardiac surgical populations, while evidence for other drugs remains inconclusive. Overall, certainty was low to very low, highlighting the need for further high-quality randomised trials to ensure generalisability.
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