Association of Inpatient Prescribing of First-Generation Antihistamines With Delirium in Older Adults: A Cross-Sectional Study

Abstract

Background: Small studies have reported associations between first-generation antihistamines and delirium. It is unclear whether first-generation antihistamines cause clinically important delirium among older adult inpatients.

Objective: To estimate the association between inpatient physician prescribing of first-generation antihistamines and delirium among older general medicine inpatients.

Methods: Cross-sectional study using the GEMINI database of inpatient admissions between April 1, 2015, and March 31, 2022, across 17 hospitals in Ontario, Canada, among people aged 65 years and older. The main exposure was the proportion of attending physicians' admissions by quartile that included a first-generation antihistamine prescription. The primary outcome was inpatient delirium identified using a machine learning tool. We estimated the association between attending physicians' first-generation antihistamine prescribing rate and individual inpatients' risk of delirium using multivariable mixed-effects logistic regression.

Results: Among 328,140 inpatient admissions to 755 physicians, 11,507 (3.5%) admissions included a first-generation antihistamine prescription. Physicians in the lowest quartile prescribed a first-generation antihistamine during 2.1% of admissions compared to 5.4% of physicians in the highest quartile. Delirium occurred in 32.3% of admissions to the lowest-prescribing quartile and 36.6% of the highest-prescribing quartile of physicians. In adjusted analyses, every 1% absolute increase in first-generation antihistamine prescribing was associated with 8% increased odds of delirium (aOR: 1.08, 95% CI: 1.05-1.10). Patients admitted to physicians in the highest quartile had 41% increased odds of delirium compared to the lowest quartile (aOR: 1.41, 95% CI: 1.28-1.56).

Conclusions: Older adults admitted to physicians who prescribe first-generation antihistamines more commonly were more likely to experience delirium in the hospital.

Keywords: delirium; drug safety; epidemiology; geriatrics; inpatient medicine.