What are the risks of anticholinergic effects with hydroxyzine (antihistamine)?

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From the Guidelines

Hydroxyzine carries significant anticholinergic effects that can increase the risk of morbidity and mortality, particularly in elderly patients, and patients should be aware of these risks before use. The anticholinergic effects of hydroxyzine include dry mouth, blurred vision, urinary retention, constipation, confusion, and cognitive impairment 1. These effects occur because hydroxyzine blocks muscarinic acetylcholine receptors in addition to its primary antihistamine action. Elderly patients are particularly vulnerable to these side effects, which can worsen cognitive function, and potentially contribute to delirium, falls, and other adverse outcomes 1.

Some key points to consider when prescribing hydroxyzine include:

  • Using the lowest effective dose (typically starting at 10-25mg for adults) to minimize risks
  • Avoiding combination with other medications that have anticholinergic properties to prevent additive effects and increased toxicity
  • Monitoring patients for anticholinergic symptoms, particularly elderly patients or those with certain conditions like glaucoma, prostatic hyperplasia, or urinary retention
  • Considering alternative antihistamines with lower anticholinergic activity, such as loratadine or cetirizine, if anticholinergic symptoms become problematic 1

It is essential to weigh the benefits and risks of hydroxyzine use, particularly in vulnerable populations, and to closely monitor patients for adverse effects to minimize morbidity and mortality. The most recent and highest quality study 1 highlights the importance of considering the anticholinergic burden of medications like hydroxyzine in older adults, and the need for careful prescribing and monitoring to prevent adverse outcomes.

From the FDA Drug Label

Anticholinergic: Dry mouth The anticholinergic effects of hydroxyzine include dry mouth.

  • Key risks: Anticholinergic effects may be a concern, particularly in patients with pre-existing conditions or those taking concomitant medications that may exacerbate these effects. 2 2

From the Research

Anticholinergic Effects of Hydroxyzine

  • Hydroxyzine, an antihistamine, has anticholinergic effects, which can pose risks to patients, especially when driving 3.
  • The anticholinergic effects of hydroxyzine can include dry mouth, constipation, visual impairments, confusion, delirium, and severe cognitive decline 4.
  • Antihistamines, including hydroxyzine, can cause significant autonomic and central nervous system effects, as well as direct cardiac toxicity 5.

Risks and Side Effects

  • Hydroxyzine is associated with a higher rate of sleepiness/drowsiness compared to other anxiolytic agents 6.
  • The use of hydroxyzine can lead to anticholinergic toxicity, particularly in elderly patients, which can result from the cumulative anticholinergic burden of multiple prescription medications and metabolites 4.
  • Hydroxyzine has been shown to be effective in alleviating the acute symptoms of generalized anxiety disorder (GAD), but its use is not without risks, and it may not be recommended as a reliable first-line treatment due to the high risk of bias in included studies 6.

Comparison with Other Medications

  • Hydroxyzine has been compared to other medications, such as haloperidol, in the treatment of delirium, and has been shown to be not inferior in terms of time to delirium improvement and superior in terms of rate of delirium improvement 7.
  • Compared to other anxiolytic agents, such as benzodiazepines and buspirone, hydroxyzine has been shown to be equivalent in terms of efficacy, acceptability, and tolerability 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Anticholinergic effects of medication in elderly patients.

The Journal of clinical psychiatry, 2001

Research

Non-traumatic rhabdomyolysis complicating antihistamine overdose.

Journal of toxicology. Clinical toxicology, 1993

Research

Hydroxyzine for generalised anxiety disorder.

The Cochrane database of systematic reviews, 2010

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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