What do current guidelines say about treating allergies with Benadryl?

The Pediatric Insider

© 2017 Roy Benaroch, MD

Last week, I published an essay titled Goodbye, Benadryl – It is time for you to retire. It generated, to use a precise term, a butt-ton of comments, almost all of which vehemently disagreed with my assertion that Benadryl is neither the safest nor most effective choice for most allergic symptoms. Here, I’ve revised the topic, looking at the most-recent published guidelines on the topic of allergies and their treatment.

Executive summary (tl; dr)

A large number of well-documented, authoritative guidelines on the treatment of allergic rhinitis and urticaria call for the use of newer antihistamines for the first line treatment of these common manifestations of allergic disease. Benadryl (diphenhydramine) is no longer recommended as first-line treatment because it works more slowly, is less effective, and is less safe. Benadryl may be useful for other conditions, but it should not be considered the first line therapy for most common allergic diseases.

 

Introduction

A Pubmed search was undertaken to find current guidelines from national or international health organizations on the treatment of allergic rhinitis and urticaria. These two diseases were chosen because they are by far the most common allergic indications for the use of diphenhydramine. I included guidelines I could find that focused on children and/or adults, mostly from 2015 and later.

The most definitive statement on the recommended use of antihistamines from these guidelines will be reported. Interested parties are encouraged to review the links for supporting documentation – these guidelines often have hundreds of references, and I’m not going to reproduce them here. Some passages will be bolded for emphasis.

In these reports, “second-generation” and “newer, non-sedating” antihistamines typically include cetirizine, loratadine, and fexofenadine; they may also include other agents that are less widely used here. “Older”, “first-generation”, or similar terms typically refer to diphenhydramine, chlorpheniramine, and other products.

 

Guidelines for the treatment of allergic rhinitis (“hay fever”)

From Clinical Practice Guideline: Allergic Rhinitis from Otolaryngology-Head and Neck Surgery (2015): “The development group also made a strong recommendation that clinicians recommend oral second-generation/less sedating antihistamines for patients with AR and primary complaints of sneezing and itching.”

From International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (2018): “The AAO‐HNS concluded, based upon RCTs and a preponderance of benefit over harm, a “strong recommendation” for the use of newer‐generation oral H1 antihistamines for patients with AR….a favorable risk‐benefit ratio was determined for using newer‐generation oral H1 antihistamines over first‐generation oral antihistamines.1170 The evidence was further strengthened with several meta‐analyses of the current data, where accurate and robust effect estimations can be derived from a large population1171.

From Allergic Rhinitis, published as part of a series “Practical guide for allergy and immunology in Canada 2018”: “Second-generation oral antihistamines and intranasal corticosteroids are the mainstay of treatment.”

From Treatment of Seasonal Allergic Rhinitis: An evidence-based focused 2017 guideline update: “Antihistamines are available as oral (first- and second-generation) and intranasal preparations. First-generation antihistamines (eg, diphenhydramine, chlorpheniramine, and hydroxyzine) cross the blood-brain barrier easily and bind central H1-receptors abundantly, which can cause sedation. They also lack specificity because cross-binding also occurs with cholinergic, a-adrenergic, and serotonergic receptors, which can cause dry mouth, dry eyes, urinary retention, constipation, and tachycardia.18 Cumulative use of first-generation antihistamines with strong anticholinergic properties has been associated with higher risk of dementia.19 In contrast, second generation antihistamines (eg, fexofenadine, cetirizine, levocetirizine, loratadine, desloratadine, ebastine, epinastine, and bilastine) are more specific for peripheral H1-receptors and have limited penetration of the blood-brain barrier, thus reducing sedation.”

From Allergic Rhinitis, a clinical guideline from the American Academy of Family Physicians (2015): “Oral second-generation/less sedating antihistamines should be prescribed for patients with AR and primary complaints of sneezing and itching.”

It is clear that every major guideline for the treatment of AR prefers newer antihistamines over diphenhydramine. None of these agents, though, are as effective as other agents such as inhaled corticosteroids.

 

Guidelines for the treatment of urticaria (hives)

From BSACI guideline for the management of chronic urticaria and angioedema (2015): “Pharmacological treatment should be started with a standard dose of a non‐sedating H1‐antihistamine (grade of recommendation = A).”

From Clinical practice guideline for diagnosis and management of urticaria (2016) “With regard to side effects, EAACI/GA2LEN/DEF/WAO Guideline 2013 recommends the use of first-generation (sedating) -antihistamines only when second-generation non-sedating antihistamines are not available.”

From Consensus on the diagnostic and therapeutic management of chronic spontaneous urticaria in adults – Brazilian Society of Dermatology (2019): “Oral antihistamines are key drugs in the treatment of chronic urticaria, especially nonsedating and low-sedating agents… According to the Urticaria International Guideline, as second-line of treatment, use of up to fourfold doses of second-generation antihistamines is indicated, whenever licensed dose failed to control the disease. , The use of these drugs at maximum doses, such as desloratadine 20 mg/day, levocetirizine 20 mg/day, loratadine 40 mg/day, and cetirizine 40 mg/day, is not yet approved in Brazil, despite published international scientific literature.”

From Management of chronic urticaria in children: a clinical guideline, Italian Journal of Pediatrics (2019): “Question 20. What is the drug of choice for CU? Recommendation. Second-generation H1-antihistamines are the first-choice treatment for CU (Level of evidence I. Strength of recommendation B).”

The overwhelming consensus from multiple international guidelines supports the use of newer antihistamines over older agents.

 

Guidelines on the use of antihistamines

From CSACI position statement: Newer generation H1-antihistamines are safer than first-generation H1-antihistamines and should be the first-line antihistamines for the treatment of allergic rhinitis and urticaria (2019): “The Canadian Society of Allergy Clinical Immunology (CSACI) recommends that newer generation AHs should be preferred over first-generation AHs for the treatment of allergic rhino-conjunctivitis and urticaria.” This article summarized in a media account, here.

In addition, an extensive review from 2010 concluded, “This review raises the issue of better consumer protection by recommending that older first‐generation H1‐antihistamines should no longer be available over‐the‐counter as prescription‐free drugs for self‐medication of allergic and other diseases now that newer second‐ generation nonsedating H1‐antihistamines with superior risk/benefit ratios are widely available at competitive prices.”

 

Conclusion

Benadryl (diphenhydramine) and other older or first-generation antihistamines should not be considered first line therapy for urticaria or allergic rhinitis.

 

Caveats

There are certainly other uses of diphenhydramine, as an agent to treat extrapyramidal side effects and perhaps as a mild sedative. It can also be used to treat motion sickness and nausea. Evidence for its usefulness for nonspecific cough and cold symptoms is lacking, though it’s often included in multi-symptom “cold relief” medications. These should not be used under age 4, and should have a limited role in reducing symptoms in older children and adults as well.

Diphenhydramine is among the only antihistamines available for parenteral use, which can be uniquely advantageous in limited circumstances where use of an oral agent is not possible.

Though often used in a setting of serious allergic reactions, anaphylaxis should always be treated with epinephrine, not an antihistamine. Antihistamines can be considered adjunctive therapy for these reactions, but epinephrine should never be delayed while giving an antihistamine or awaiting a response to an antihistamine.

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