Antihistamines’ role in Delirium: A systematic review and meta-analysis of observational studies

Abstract

Delirium is a prevalent condition, especially in intensive care units, postoperative settings, and long-term care facilities. While H1 and H2 Histamine receptor antagonists (H1RAs and H2RAs) are widely used, due to their sedative and anticholinergic activities, their impact on delirium remains controversial. This study aimed to quantify the association between antihistamine and delirium in the adult population. This systematic review and meta-analysis of observational studies followed PRISMA guidelines. Five online databases (PubMed, Scopus, Embase, CINAHL, and Web of Science), were searched from inception to July 2026. A meta-analysis of the overall effect, with subgroup analyses of postoperative delirium (POD) and non-surgical delirium (Delirium) was performed. Risk of Bias was assessed using the Joanna Briggs Institute Critical Appraisal tools. Pooled odds ratios (OR) were calculated using random-effects models. 24 observational studies were included, of which 22 contributed to the meta-analysis. Antihistamine exposure was robustly associated with an increased risk of All-cause delirium (OR = 1.26, 95% CI: 1.08–1.47, I 2 = 85.2%). Also, antihistamines showed a significant association with Delirium (OR = 1.24, 95% CI: 1.05–1.46, I 2 = 89.4%). Subgroup analyses showed that H2RAs had a significant and fragile association with All-cause delirium and Delirium and H1RAs with Delirium. H1RAs showed a significant association with Delirium, and H2RAs showed a significant association with All-cause delirium and non-surgical delirium, and an overall antihistamine association with all-cause delirium and non-surgical delirium. Due to the inherent limitation of observational studies, findings should be interpreted with caution.

The authors' abstract, as published at the source. Aging Clinical and Experimental Research, 2026 · DOI ↗