For decades, diphenhydramine—best known by the brand name Benadryl—has been a go-to medication for relieving allergy symptoms, such as runny noses, watery eyes, and rashes. But despite its longstanding presence in many medicine cabinets, some experts say it’s time to retire the popular drug.
The drug’s side effects and other risks are so concerning that it should no longer be readily available over the counter or widely prescribed, several doctors argued in a paper published in the World Allergy Organization Journal earlier this year titled “Diphenhydramine: It is time to say a final goodbye.”
“If Benadryl underwent clinical trials today, in my opinion, it would certainly not be approved for the OTC market due to adverse reactions,” Lawrence B. Schwartz, MD, PhD, an allergy and immunology specialist at VCU Health who did not work on the paper, told Health.
Here’s why Schwartz and others say it’s time to move on from Benadryl—and whether that means you should, too.
Diphenhydramine can be taken by adults and children and is used to treat seasonal allergies, hives, motion sickness, and insomnia, according to the American Academy of Allergy, Asthma and Immunology.
The medication is what’s known as a “first-generation” antihistamine, meaning that it’s an older drug that works by binding to and blocking the body’s histamine receptors, specifically the H1 receptors. Cells throughout the body produce histamine during allergic reactions in blood vessels, airways, and nerves, and it’s also produced in the brain and plays a part in wakefulness.
Approved as a prescription drug in 1946 and over the counter in the 1980s, diphenhydramine is now available in approximately 300 formulations either on its own or combined with other ingredients. While there’s no available data on OTC use, more than 1 million prescriptions for stronger versions of diphenhydramine are written in the United States every year.
Benadryl is widely used because it’s affordable—the average prescription costs less than $8—and can effectively treat a variety of allergy-related symptoms, from watery, itchy eyes to hives and bug bite reactions, according to the recent paper.
Like all antihistamines, Benadryl causes drowsiness by blocking H1 receptors and crossing the blood-brain barrier.
But it also does other things that can create side effects. For instance, it blocks sodium channels, helping it to act as a local anesthetic and potentially leading to dangerous cardiac effects.
Additionally, it can cause dry mouth, blurry vision, constipation, urinary retention, and an elevated heart rate because it blocks acetylcholine, a neurotransmitter in the central nervous system, Trisha Ray, MD, clinical director of Allergy and Immunology at Beth Israel Deaconess Medical Center, told Health.
Due to these significant side effects, manufacturers eventually developed “second-generation” antihistamines, such as loratadine (Claritin), cetirizine (Zyrtec), or fexofenadine (Allegra), to offer gentler options for the body.
These newer medications bind only to H1 receptors and cross the blood-brain barrier at much lower levels than Benadryl, making them less likely to cause drowsiness and other adverse effects, said Ray.
Some experts say that second-generation antihistamines are simply safer than Benadryl.
Benadryl’s sedating effects—so effective that the pharmaceutical industry began marketing it as a sleep aid in the 1970s—can affect concentration, attention, memory, and performance well into the next day, authors of the February paper noted.
“Patients are frequently unaware of the potential for these well-established effects,” said James H. Clark, MD, the co-director of the Johns Hopkins Dysphagia and Deglutition Clinic at The Johns Hopkins School of Medicine and a co-author of the paper. “This scenario has resulted in vehicular accidents in patients who have underestimated their sedation after taking such medications.”
One study found that a single dose of diphenhydramine impaired driving more than a 0.1% blood alcohol level, but fexofenadine (Allegra) did not affect driving.
Experts cite other reasons Benadryl should be phased out, including its ability to cause:
- Additional side effects, such as heart rhythm disruptions, constipation, urinary retention, dry eyes, blurry vision, and skin flushing
- Cognitive effects, such as an increased risk of confusion and dementia, including Alzheimer’s, from cumulative use in adults ages 65 and up
- An increased risk of agitation and confusion in children, which can be followed by extreme sedation and coma
- Potential for abuse, as illustrated by the TikTok “Benadryl Challenge” that led to hospitalizations and deaths
While no direct head-to-head studies have compared the effectiveness of second-generation medications with that of Benadryl, numerous studies suggest that these medications relieve allergy symptoms as effectively, with fewer side effects, the paper’s authors said.
“The presence of effective and safer second-generation antihistamines, frequent and sometimes severe adverse reactions to first-generation agents, as well as its demonstrated abuse potential, strongly suggest it is time to remove diphenhydramine’s availability from both the prescription and over-the-counter markets,” they concluded.
The study authors aren’t the only ones who advise against Benadryl as a first-line defense.
In guidance from 2020, the American Academy of Allergy, Asthma, and Immunology and the American College of Asthma, Allergy, and Immunology recommends that when treating rhinitis, a collection of symptoms affecting the nose and nasal passages, clinicians prescribe second-generation oral antihistamines over first-generation options to reduce the risk of adverse effects. Many global guidelines also favor second-generation antihistamines for hives and rhinitis.
For those with chronic allergies, second-generation antihistamines are superior not only because they have fewer side effects but also because they last longer, allowing for consistent use at higher doses, said Ray.
But Benadryl still has its place in certain situations, Jessica Hui, MD, a pediatric allergist and immunologist at National Jewish Health, told Health.
For example, Benadryl can be preferable if you don’t want to take a medication that lasts as long in the body or in situations where drowsiness is desired, such as before a procedure, said Hui.
In cases of acute allergic reactions or anaphylaxis, Benadryl’s rapid onset of action—15 to 30 minutes versus 20 to 60 minutes for second-generation antihistamines—can also make it the top choice, explained Ray.
“This may not be a major difference in most cases, but in my clinical experience, I have witnessed firsthand the rapid improvement in symptoms from administration of Benadryl in an acute setting,” she said.
Other than select uses, Hui said she advises allergy sufferers to turn to second-generation antihistamines for relief. “In general,” she said, “second-generation antihistamines will be safer, especially in populations like the elderly.”
