A recent comprehensive study published in the esteemed Journal of the American Geriatrics Society sheds new light on the complex relationship between the inpatient prescribing habits of first-generation antihistamines and the onset of delirium among older hospitalized adults. This research presents a critical evaluation of the risks associated with these medications, which, despite their common use, may contribute substantially to adverse cognitive outcomes in a vulnerable population.
First-generation antihistamines, including well-known agents such as diphenhydramine, are traditionally utilized for the management of allergic reactions, including urticaria and anaphylaxis, due to their histamine H1 receptor antagonism. However, their pharmacological profile encompasses pronounced anticholinergic and sedative properties, which are increasingly implicated in contributing to medication-related harms. These effects are particularly concerning in geriatric patients, who are physiologically more susceptible to central nervous system side effects due to altered pharmacodynamics and pharmacokinetics inherent to aging.
The investigators conducted a rigorous population-based cohort study spanning from 2015 to 2022, encompassing data from 328,140 patients aged 65 and older admitted to 17 hospitals in Ontario, Canada. These patients were managed by 755 attending physicians whose prescribing patterns of first-generation antihistamines were meticulously analyzed. The study identified an alarmingly high overall delirium prevalence rate of 34.8% among the inpatient cohort, a statistic that underscores the pervasive nature of cognitive disturbances in hospitalized elderly patients.
Significantly, the findings reveal that patients admitted under the care of physicians with higher rates of first-generation antihistamine prescriptions exhibited a 41% increase in the odds of developing delirium compared to those treated by physicians who rarely prescribed these agents. This association persisted even after adjusting for confounding variables, suggesting a robust link between the use of sedating antihistamines and cognitive impairment during hospitalization. The study’s methodological strengths, including its vast sample size and multi-institutional data collection, lend considerable weight to the validity of these outcomes.
Delirium, characterized by an acute fluctuating disturbance in attention and cognition, poses a grave clinical challenge in geriatric medicine given its association with increased morbidity, extended hospital stays, and elevated mortality rates. The pathophysiological underpinnings of delirium are multifactorial, often involving neurotransmitter imbalances, systemic inflammation, and alterations in brain metabolism. Medications with anticholinergic activity exacerbate these disturbances by precipitating cholinergic deficits, further impairing cognitive function. Therefore, the iatrogenic contribution of antihistamines, many of which share such properties, demands careful reevaluation in clinical practice.
Current prescribing practices may inadvertently place elderly inpatients at heightened risk due to the frequent utilization of first-generation antihistamines in hospital settings, either for allergic reactions or off-label uses such as sleep aid or anxiety management. This study highlights the critical need to balance therapeutic benefits with potential harms, particularly when safer alternatives, including second-generation antihistamines with minimal sedative effects, are available. Moreover, increased awareness among hospitalists and multidisciplinary teams regarding the psychotropic side effects of these medications is imperative to enhance patient safety.
Corresponding author Dr. Aaron M. Drucker of the University of Toronto and Women’s College Hospital emphasized the importance of judicious prescription, stating that the sedative nature of first-generation antihistamines should compel healthcare providers to exercise caution, especially when treating elderly patients at risk for cognitive decline. This call to action aligns with broader initiatives aiming to minimize polypharmacy and promote deprescribing strategies tailored toward preserving mental faculties in aging populations.
Mechanistically, first-generation antihistamines readily cross the blood-brain barrier, antagonizing central histamine receptors and precipitating sedation. Their anticholinergic effects further disrupt neurotransmitter networks vital for cognition and alertness. In older adults, these pharmacological actions are magnified by age-related decreases in hepatic and renal clearance, enhancing both the intensity and duration of drug effects. Such factors cumulatively contribute to the observed vulnerability to delirium among hospitalized seniors receiving these medications.
This landmark study also opens avenues for future research to explore the pathogenesis of medication-induced delirium, potentially incorporating pharmacogenomic profiling to identify patients with heightened sensitivity. Moreover, longitudinal investigations could determine whether minimizing or avoiding first-generation antihistamines translates to lower delirium incidence and improved clinical outcomes, fostering evidence-based guidelines for safer prescribing in geriatrics.
In light of these findings, healthcare institutions may consider implementing clinical decision support tools and educational programs that alert prescribers to the risks associated with first-generation antihistamines. Integrating such measures within electronic health record systems could curtail unnecessary prescriptions, promote alternative therapies, and ultimately ameliorate the burden of delirium on patients, caregivers, and healthcare resources.
To conclude, this study underscores a profound and clinically relevant association between the inpatient use of first-generation antihistamines and the heightened risk of delirium in older adults. Its implications resonate across geriatric medicine, hospital medicine, pharmacology, and patient safety initiatives, calling for an urgent reassessment of antihistamine prescribing paradigms. As the aging population continues to grow globally, optimizing medication regimens to safeguard cognitive health remains a paramount priority.
Subject of Research: Medication prescribing patterns of first-generation antihistamines and their association with delirium risk in hospitalized older adults
Article Title: Association of inpatient prescribing of first-generation antihistamines with delirium in older adults
News Publication Date: 22-Oct-2025
Web References:
- Journal of the American Geriatrics Society: https://agsjournals.onlinelibrary.wiley.com/journal/15325415
- DOI link to the article: http://dx.doi.org/10.1111/jgs.70121
Keywords: Antihistamines, Older adults, Hospitals, Delirium, Geriatrics, Epidemiology, Drug safety
