What is the controversy surrounding Diphenhydramine (Benadryl) and what are the preferred alternatives?

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Last updated: May 5, 2025View editorial policy

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From the Guidelines

Benadryl (diphenhydramine) is not a preferred treatment option due to its significant side effects, and second-generation antihistamines like Claritin (loratadine), Zyrtec (cetirizine), Allegra (fexofenadine), and Xyzal (levocetirizine) are recommended as safer alternatives. The controversy surrounding Benadryl stems from its potential to cause sedation, performance impairment, and anticholinergic effects, which can be particularly problematic in older adults and children 1.

Side Effects of Benadryl

The use of Benadryl has been associated with:

  • Sedative effects, including drowsiness and performance impairment
  • Anticholinergic effects, such as dry mouth, constipation, and increased risk of narrow angle glaucoma
  • Paradoxical CNS stimulation, particularly in children
  • Potential cognitive impairment and increased dementia risk with long-term use

Preferred Alternatives

Second-generation antihistamines are generally preferred over first-generation antihistamines like Benadryl due to their lower likelihood of adverse effects 1. These alternatives include:

  • Claritin (loratadine): 10mg daily
  • Zyrtec (cetirizine): 10mg daily
  • Allegra (fexofenadine): 180mg daily
  • Xyzal (levocetirizine): 5mg daily

Sleep Aid Alternatives

For those seeking sleep aid, dedicated sleep medications or melatonin are safer options than using Benadryl regularly 1. The American Academy of Sleep Medicine suggests using eszopiclone, zaleplon, or zolpidem as treatment for sleep onset and sleep maintenance insomnia, rather than diphenhydramine.

Important Considerations

It is essential to consult with a healthcare provider before switching medications, especially for children, pregnant women, or those with chronic conditions. Additionally, older adults should be cautious when using first-generation antihistamines due to their increased sensitivity to psychomotor impairment and adverse anticholinergic effects 1.

From the Research

Controversy Around Benadryl

  • The controversy around Benadryl, also known as diphenhydramine, stems from its potential to cause adverse effects on the central nervous system, such as sedation and impairment of cognitive function 2, 3.
  • Diphenhydramine is a first-generation antihistamine, which can lead to complications in discharge planning from emergency departments due to its sedative effects 2.

Preferred Alternatives

  • Newer, second-generation antihistamines, such as loratadine, desloratadine, cetirizine, and fexofenadine, are considered safer alternatives to Benadryl, causing less sedation and similar efficacy 2, 3, 4, 5.
  • These second-generation antihistamines are preferred for managing acute allergic reactions, especially when sedation is a concern, due to their lower risk of adverse effects and similar efficacy to first-generation antihistamines 2, 3.
  • Cetirizine and fexofenadine are noted for their faster onset of action and lower incidence of sedation compared to diphenhydramine, making them suitable options for patients requiring quick relief from allergic symptoms 2, 5.
  • The choice of antihistamine should be based on the severity and frequency of symptoms, as well as patient preference, with second-generation antihistamines being the preferred first-line treatment option for allergic rhinitis and urticaria 4, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

First do no harm: managing antihistamine impairment in patients with allergic rhinitis.

The Journal of allergy and clinical immunology, 2003

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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