By Jennifer Henderson

A paper that calls for saying a "final goodbye" to diphenhydramine -- best known as Benadryl -- has physicians talking on social media.

Published in the World Allergy Organization Journal, the paper gives several reasons why it's time to move on from Benadryl, including the "presence of effective and safer second-generation antihistamines, frequent and sometimes severe adverse reactions to first-generation agents, [and] its demonstrated abuse potential."

Lead author James Clark, MD, of Johns Hopkins University School of Medicine in Baltimore, noted that despite its known downsides, use of diphenhydramine in both prescription and over-the-counter forms remain prevalent in the U.S.

"Often when patients come into my clinic, they're already on an oral antihistamine, and it will be something like Benadryl," said Clark. "I see it quite frequently in kids too, and it's talking to their parents and trying to educate them on the different options and the potential downsides of Benadryl as a medication."

Other experts in allergy and immunology agree, and have recently started sharing the paper on social media, though it was published earlier this year.

"Anything you would use Benadryl for can be replaced with cetirizine (Zyrtec), loratadine (Claritin), fexofenadine (Allegra), or [levocetirizine (Xyzal)]," David Stukus, MD, of Nationwide Children's Hospital in Columbus, Ohio, wrote in an Instagram post about the paper. "If you're asking if any of these are safer or better, the answer is YES!!!"

"Can I use one of these for an acute allergic reaction? Yes!" he added. "Hives? Yes! Seasonal allergies? Yes! What if I take one of these daily and need another one? Yes! The answer is going to be yes!"

Diphenhydramine is a non-selective binder; it doesn't only target histamine receptors in the body, said Stukus. "It actually binds to receptors throughout the body, and it can impact just about any organ system," he said, and accordingly, there can be significant side effects.

In their paper, Clark and colleagues said diphenhydramine can interfere with sleep quality, and side effects include sedation, drowsiness, and psychomotor impairment. They also cited the TikTok "Benadryl challenge" during the pandemic -- which led to deaths and hospitalizations -- as an example of its abuse potential.

"Diphenhydramine is not recommended for people with specific health problems, including closed-angle glaucoma, dry eyes, peptic ulcer, constipation, and urinary retention," they wrote. "In addition, regular use of diphenhydramine poses risks for women who are pregnant or breastfeeding. Due to anticholinergic properties, cumulative use of first-generation antihistamines confers risks for people over age 65, including Alzheimer's disease and other forms of dementia."

Conversely, second-generation antihistamines "mostly target histamine receptors with very few side effects," Stukus said.

"They also have equivalent onset and longer-lasting treatment effects," Clark and colleagues wrote in the paper. "Thus, they have much better therapeutic ratios than diphenhydramine." And they are similarly priced and widely available, they added.

Stukus added that he shared the paper because "people are getting their information on social media these days, and that's part of the reason that I'm out there."

Zachary Rubin, MD, a pediatrician specializing in allergy and immunology who practices near Chicago, said in a post on Instagram that "while [Benadryl] is one of the oldest antihistamines available, [that] does not mean that it is the most effective, nor is it the most safe."

Neither the American College of Allergy, Asthma, & Immunology nor the American Academy of Allergy, Asthma, & Immunology (AAAAI) has an official policy or recommendations about the use of Benadryl.

However, AAAAI's Rhinitis Practice Parameter from 2020 recommends against prescribing first-generation antihistamines such as Benadryl in favor of second-generation antihistamines for allergic rhinitis.

Outside the U.S., there are countries that have moved -- at least in part -- away from diphenhydramine. In their paper, Clark and colleagues noted that Germany, the Netherlands, and Sweden have taken action to make diphenhydramine available by prescription only, and that the Canadian Society of Allergy and Clinical Immunology has recommended first-generation antihistamines be considered solely as behind-the-counter medications.

However, it is unlikely that diphenhydramine will disappear from the U.S. market, experts said.

"Benadryl has its place," Rubin said. "When you talk about intravenous antihistamines, that's the only one that's readily available in most places."

He also emphasized that any time a person is making certain changes related to their health, it is important they talk with their doctor about it, "because every case is unique."

"Science involves evolution and accumulation of evidence, and we should always be looking at best practices," Stukus said. "Why are we doing the things we're doing today, not just from a practice level ... but on a patient level." He said he believes the larger message is that this is just one of many examples because medicine is lifelong learning.

"If a patient has been taking a medication for years and years, we should always be reevaluating," he continued. "Do they actually need that? Are there better options available? We should revisit things over time."