Acetylcholinesterase Inhibitors for Delirium Prevention: A Systematic Review and Meta-Analysis

OBJECTIVES: Delirium is a frequent complication in hospitalized patients, particularly in older adults, and is associated with significant morbidity and mortality. Acetylcholinesterase inhibitors (AChEIs) have been proposed as potential agents to reduce occurrence and severity of delirium. This study aimed to evaluate the efficacy of AChEIs for both prophylaxis and treatment of delirium in hospitalized patients. DATA SOURCES: We searched PubMed, Embase, and Web of Science. The study was registered on PROSPERO (CRD42024563798). STUDY SELECTION: Studies comparing AChEIs and placebo for delirium in hospitalized patients. DATA EXTRACTION: The main outcome of interest was delirium occurrence, while secondary outcomes included duration, severity, and hospital length of stay (LOS). DATA SYNTHESIS: Subgroup analyses were performed based on prophylaxis or treatment of delirium. Statistical analysis was performed in RStudio 4.4.0 with a random effects model, and heterogeneity was assessed with I2 . Risk of Bias 2 was used for bias assessment. We screened 1306 records and included ten studies: eight studies focusing on prophylaxis after surgery and two on treatment of established delirium. A total of 731 patients were analyzed: 365 in the AChEIs group and 366 in the placebo group. AChEIs significantly reduced delirium occurrence (risk ratio = 0.68 [0.47-0.98]; p = 0.039). No significant effects were observed for delirium duration (mean difference [MD] = -0.16 d [-0.9 to 0.62 d]; p = 0.23), delirium severity (standardized mean difference [SMD] = -0.08 [-0.58 to 0.41]; p = 0.74), or LOS (MD = -0.82 d [-2.03 to 0.40 d]; p = 0.19). Subgroup analysis showed a tendency for better outcomes when AChEIs were used as prophylaxis, with a significant reduction in delirium duration in this subgroup (SMD= -0.32 [-0.56 to -0.07]; p < 0.01). No significant differences in adverse events were identified. CONCLUSIONS: AChEIs are effective in reducing occurrence of delirium when used prophylactically in patients undergoing elective surgery. AChEIs did not significantly impact on delirium duration, severity, or hospital LOS. Further studies are needed to explore the potential benefits or harms of AChEIs in different patient populations and settings.