What is the comparison between diphenhydramine (Benadryl) and hydroxyzine (Vistaril)?

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From the Guidelines

Diphenhydramine and hydroxyzine are both first-generation antihistamines, but hydroxyzine is generally considered a better option due to its additional anxiolytic effects and potential benefits in treating interstitial cystitis/bladder pain syndrome, as shown in a 2022 study 1. When comparing diphenhydramine and hydroxyzine, it's essential to consider their sedative effects, anticholinergic properties, and potential for performance impairment.

  • Both medications can cause sedation, drowsiness, and impaired cognitive function, especially in older adults or when combined with other CNS-active substances 1.
  • Hydroxyzine has been shown to be effective in treating anxiety and allergies, with doses ranging from 10mg to 50mg, and its effects can last for 4-6 hours 1.
  • Diphenhydramine, on the other hand, is not recommended as a treatment for sleep onset and sleep maintenance insomnia in adults, according to a 2017 clinical practice guideline 1.
  • A 2008 study suggests that first-generation antihistamines like diphenhydramine and hydroxyzine can have significant anticholinergic effects, including dry mouth, constipation, and increased risk of narrow-angle glaucoma 1.
  • However, hydroxyzine has been found to have potential benefits in treating interstitial cystitis/bladder pain syndrome, with clinically significant improvement compared to placebo, as shown in a 2022 study 1. Overall, while both medications have their uses and side effects, hydroxyzine is generally considered a better option due to its additional anxiolytic effects and potential benefits in treating interstitial cystitis/bladder pain syndrome.

From the Research

Comparison of Diphenhydramine (Benadryl) and Hydroxyzine (Vistaril)

There are no direct comparisons between diphenhydramine (Benadryl) and hydroxyzine (Vistaril) in the provided studies. However, the studies provide information on the efficacy and side effects of hydroxyzine.

Efficacy of Hydroxyzine

  • Hydroxyzine has been shown to be effective in reducing anxiety symptoms in patients with generalized anxiety disorder (GAD) 2, 3, 4.
  • Hydroxyzine has been found to be equivalent in terms of efficacy to other anxiolytic agents such as benzodiazepines and buspirone 2.
  • Hydroxyzine has also been used to reduce stress and anxiety associated with coronary disease 3.

Side Effects of Hydroxyzine

  • Hydroxyzine has been associated with a higher rate of sleepiness/drowsiness compared to other anxiolytic agents 2.
  • Common side effects of hydroxyzine include sleepiness, weight gain, dry mouth, loss of concentration, and insomnia 4.
  • Sleepiness is often transient and disappears later during treatment 4.

Other Uses of Hydroxyzine

  • Hydroxyzine has been used in the treatment of interstitial cystitis, with preliminary results indicating its effectiveness in reducing symptoms 5.
  • Hydroxyzine has been used in combination with morphine to relieve pain and anxiety in patients with acute severe pain, but its addition did not reduce pain or anxiety in one study 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hydroxyzine for generalised anxiety disorder.

The Cochrane database of systematic reviews, 2010

Research

Recent clinical trials of hydroxyzine in generalized anxiety disorder.

Acta psychiatrica Scandinavica. Supplementum, 1998

Research

Hydroxyzine in the treatment of interstitial cystitis.

The Urologic clinics of North America, 1994

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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