J Am Geriatr Soc

First-generation antihistamines tied to higher delirium risk in hospitalized older adults

October 28, 2025

Study details: This cross-sectional study analyzed 328,140 admissions of adults aged ≥65 years across 17 hospitals in Ontario (2015–2022), using the GEMINI database. The exposure was the quartile of attending physicians' first-generation antihistamine prescribing rates. Delirium was identified via a validated machine learning tool. Multivariable mixed-effects logistic regression adjusted for confounders.

Results: First-generation antihistamines were prescribed in 3.5% of admissions overall. Physicians in the lowest quartile prescribed a first-generation antihistamine during 2.1% of admissions vs. 5.4% in the highest quartile. Delirium occurred in 32.3% of admissions to the lowest-prescribing quartile and 36.6% in the highest. Each 1% absolute increase in antihistamine prescribing was associated with 8% higher odds of delirium (adjusted odds ratio [aOR], 1.08; 95% confidence interval [CI], 1.05–1.10). Patients admitted to physicians in the highest quartile had 41% increased odds of delirium compared with the lowest (aOR, 1.41; 95% CI, 1.28–1.56).

Clinical impact: These findings reinforce the need for caution when prescribing first-generation antihistamines to older inpatients, given the strong association with delirium. Reducing exposure to these agents may lower delirium incidence and improve outcomes in this vulnerable population.

Source:

Bridgman AC, et al. (2025, October 22). J Am Geriatr Soc. Association of Inpatient Prescribing of First-Generation Antihistamines With Delirium in Older Adults: A Cross-Sectional Study. https://pubmed.ncbi.nlm.nih.gov/41121962/