Bye-bye Benadryl?

- Jennifer Middleton, MD, MPH

The Canadian Society of Allergy and Clinical Immunology (CSACI) released a statement last month asserting that newer generation antihistamines "should be the first-line antihistamines for the treatment of allergic rhinitis and urticaria." They cite studies demonstrating that first-generation antihistamines (diphenhydramine, chlorpheniramine, and hydroxyzine) have more worrisome side effects than newer generation antihistamines (loratidine, cetirizine, and fexofenadine), and both generations have equal treatment efficacy. They end their statement with a call to move diphenhydramine products behind the counter.

The CSACI discuses studies showing that many physicians perceive first-generation antihistamines to have a faster onset of action, but this perception is inaccurate; in one double-blind study, cetirizine and loradatine were even found to have faster onset than chlorpheniramine. First-generation antihistamines do not relieve allergic symptoms better than newer generation antihistamines, and first-generation antihistamines have more serious side effects. First-generation antihistamines have been implicated in accidental overdoses, torsades de pointes, and significant sedation. This sedation has led to the use of first-generation antihistamines as sleep aids, but they have not been found to improve the quality or duration of sleep in adults. A 2006 randomized controlled trial also found that diphenhydramine use resulted in no sleep benefit to infants.

The 2016 AFP review on "Treatment of Allergic Rhinitis" is consistent with the CSACI's statement. One of the authors' Key Recommendations for Practice states that, "[c]ompared with first-generation antihistamines, second-generation antihistamines have a better adverse effect profile and cause less sedation." Impermeable dust-mite bedding covers, household air filters, and delayed exposure to foods or pets in early childhood have not been found to benefit patients. On the other hand, nasal saline irrigation, nasal corticosteroids, and newer generation oral antihistamines all receive endorsements from the authors' evidence review.

It seems unlikely that diphenhydramine will disappear any time soon. Johnson & Johnson, the manufacturers of Benadryl, released their own statement shortly after the CSACI's: "Benadryl products have been trusted..for more than 60 years" and are "safe and effective." The lay press in the United States has not shown great interest in covering the CSACI statement, and changing well-established habits may be challenging for patients and physicians alike. Recommending safer, more effective treatments, however, can be a first step for family physicians. There's an AFP By Topic on Allergy and Anaphylaxis if you'd like to read more.