To evaluate the efficacy of acetylcholinesterase inhibitors (AChEIs) for the prevention and treatment of delirium in hospitalized patients.

Delirium is a common condition in hospitalized patients, contributing to increased morbidity and mortality. The role of AChEIs in preventing and treating delirium remains controversial.

We conducted a systematic review and meta-analysis of studies from PubMed, Embase, and Web of Science, screening articles from inception to June 2024. RCTs comparing AChEIs with placebo were included, excluding patients with chronic AChEI use. The study was registered on PROSPERO (CRD42024563798). The primary outcome was delirium incidence, while secondary outcomes included delirium duration, severity, length of hospital stay (LOS), and adverse events. Bias was assessed using the ROB2 tool, and a random-effects meta-analysis was performed. Heterogeneity was evaluated with I². Subgroup analysis compared AChEIs' efficacy for delirium prophylaxis versus treatment.

Of 1,306 records screened, 10 RCTs were included, comprising 731 patients — 365 in the AChEI group and 366 in the placebo group. Eight studies evaluated AChEIs for delirium prophylaxis initiated before or immediately after surgery, while two studies assessed AChEIs for the treatment of established delirium. AChEIs significantly reduced the incidence of delirium (RR=0.68 [0.47 - 0.98]; p=0.039). There was no significant reduction in delirium duration (MD=-0.16 days [-0.95 - 0.62]; p=0.23), severity (SMD=-0.08 [-0.58 - 0.41]; p=0.74), or LOS (MD=-0.82 days [-2.03 - 0.40]; p=0.19). Subgroup analysis showed a significant reduction in delirium severity in patients receiving AChEIs prophylactically (SMD=-0.32 [-0.56 - -0.07], p<0.01). No differences were observed in the rate of serious adverse events between groups.

AChEIs effectively reduce the incidence and severity of delirium when used prophylactically in patients undergoing surgery. However, AChEIs are not effective for treating patients who already have delirium. These findings highlight the potential role of AChEIs in delirium prevention, particularly in an older population.