# First-Generation Antihistamine Use in Geriatric Emergency Department Patients: Retrospective Review

**Authors:** Emily Killen, Michael Cusumano, Zidong Zhang, Richard Newman, Jamie Voigtmann, Angela M. Sanford, Cindy C. Bitter

PMC · DOI: 10.5811/westjem.47491 · 2025-12-31

## TL;DR

This study found that first-generation antihistamines used in older ED patients often led to adverse effects like delirium and were frequently prescribed inappropriately.

## Contribution

The study provides ED-specific data on the risks and misuse of first-generation antihistamines in geriatric patients.

## Key findings

- 15% of encounters had adverse drug effects, with delirium and urinary retention being most common.
- Patients aged ≥85, those with cognitive impairment, and those receiving multiple doses had higher risk of adverse effects.
- 92% of antihistamine use was classified as potentially inappropriate, especially for non-allergic indications.

## Abstract

First-generation antihistamines are frequently used in the emergency department (ED) but are discouraged in older adults due to increased adverse drug effects. Whether concerns about adverse drug effects apply to the ED is uncertain, as ED-specific data are limited, and risks with single-dose administration may differ from risks with chronic use. In this study we assessed frequency of use, adverse drug effects, and indications of first-generation antihistamines administered to older adults during ED visits.

This retrospective cohort study identified adults ≥ 65 years of age who received first-generation antihistamines from January 1–December 31, 2022 in the ED at a single, urban, academic medical center. Abstractors blinded to study hypotheses identified indications for use and adverse effects through chart review. Indications other than severe allergic reactions and continuation of home use were classified as potentially inappropriate. We evaluated sex, age ≥ 85, history of cognitive impairment, drug received, and number of doses for association with adverse drug effects by regression analysis.

First-generation antihistamines were administered in 261 encounters (3% of geriatric ED encounters). Median patient age was 71 (range 65–107, interquartile range [IQR] 67–77) and 60.5% were female. Adverse drug effects occurred in 15% of encounters, with delirium (n = 20, 7.7%) and urinary retention (n = 11, 4.2%) being the most common. On multivariate analysis, patient age ≥ 85, history of cognitive impairment, and receipt of multiple doses were associated with elevated risk of adverse drug effects, with risk ratios of 5.5 (95% CI, 2.7–11.4), 3.1 (95% CI, 1.8–5.4), and 1.9 (95% CI, 1.1–3.6), respectively. Indications were classified as potentially inappropriate in 92% of encounters. Diphenhydramine was most used in patients with headache (n = 53, 30.1% of doses) and history of iodinated contrast media reaction (n = 46, 26.1% of doses), while hydroxyzine was most used for anxiety (n = 51, 60% of doses). The kappa value between abstractors was 0.84, indicating excellent agreement.

Emergency department use of first-generation antihistamines in older adults, especially those ≥ 85 years of age and with prior cognitive impairment, was associated with infrequent but clinically significant harm. Most use was potentially inappropriate. Prophylactic use of diphenhydramine for patients with a prior reaction to iodinated contrast media emerged as a common indication.

## Linked entities

- **Chemicals:** diphenhydramine (PubChem CID 3100), hydroxyzine (PubChem CID 3658)
- **Diseases:** delirium (MONDO:0045057)

## Full-text entities

- **Diseases:** urinary retention (MESH:D016055), headache (MESH:D006261), delirium (MESH:D003693), cognitive impairment (MESH:D003072), allergic reactions (MESH:D004342), anxiety (MESH:D001007)
- **Chemicals:** Diphenhydramine (MESH:D004155), hydroxyzine (MESH:D006919)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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Source: https://tomesphere.com/paper/PMC12815559