Doctors are taking aim at a medicine cabinet staple, arguing its risks outweigh its benefits.
Millions of adults and children take over-the-counter (OTC) diphenhydramine, the active ingredient in Benadryl, for allergies or for its drowsiness effect to help with sleep. It is one of the most recognizable allergy medicines on pharmacy shelves for its ability to alleviate allergy-related runny nose, sneezing, itchiness and watery eyes.
But internal medicine physicians argue that the FDA should eliminate the over-the-counter medicine from the US market based on concerns about potentially severe adverse effects, including ‘substantial’ brain damage.
Diphenhydramine is a first-generation antihistamine that easily enters the brain, where it causes strong drowsiness and impairs alertness and coordination. This sedation can reduce work productivity, hurt school performance and significantly increase the risk of car accidents. In some tests, its effects on driving were more severe than being over the legal alcohol limit.
Beyond sleepiness, diphenhydramine also causes a range of uncomfortable and sometimes dangerous side effects, including dry mouth, constipation, blurred vision, confusion and urinary difficulty, which are especially risky for older adults. Young people have also overdosed on the seemingly innocuous drug.
Long-term or frequent use of Benadryl has been linked to serious heart rhythm problems and an increased risk of dementia. Its drowsiness is considered severe enough that European labels warn against driving after taking it, and US pilots are banned from using it while flying.
Newer antihistamines, like fexofenadine, used in Allegra, and loratadine, used in Claritin, developed in the late 20th century, offer equal allergy relief with fewer side effects and longer-lasting action.
Despite these advantages and being similarly priced and available over-the-counter, the older drug diphenhydramine remains one of the most popular OTC antihistamines in the US. This is partly because it is included in hundreds of products targeting allergies, colds and sleep problems.
Doctors are pushing the FDA to eliminate the popular allergy and sleep aid diphenhydramine, most commonly marketed and sold under the brand Benadryl, from stores, citing evidence of potentially severe adverse effects, including ‘substantial’ brain damage (file photo)
Physicians at the Johns Hopkins University School of Medicine and the University of California, San Diego made the case in JAMA Internal Medicine that diphenhydramine should be supplanted by second-generation antihistamines, such as like fexofenadine and desloratadine, the active ingredients in Allegra and Clarinex.
They said: ‘Widespread advertisements, entrenched prescribing habits, and self-treatment behaviors developed over decades contribute to the persistent use of diphenhydramine.
‘However, we argue that OTC availability is the major contributor to the widespread use of diphenhydramine, the under-recognition of adverse effects, and the false perception of safety.’
A drug can only be sold over-the-counter if it is widely regarded as safe and effective. If new safety concerns arise, the FDA may appoint experts to review the evidence and recommend that the product be pulled from store shelves.
Adverse effects of diphenhydramine were seen when the ‘Benadryl Challenge’ exploded on social media. Young people encouraged one another to take dangerously high doses of Benadryl to induce hallucinations.
Kenvue, the company that makes and markets Benadryl, told the Daily Mail: ‘The health and safety of people who use our products is our top priority. We take the proper use of our products very seriously and work with non-profit partners and healthcare professionals to educate on appropriate use and safe storage of OTC products, including diphenhydramine-containing products.
‘As with any OTC medicine, we recommend that consumers carefully read and follow the instructions on the label and contact their health care professional should they have questions. Dosing instructions and additional safety information can also be found on Benadryl.com.’
Physicians argue that, despite its known risks, diphenhydramine is still exceedingly popular due to self-treatment behaviors, deeply-entrenched medical orthodoxy and positive advertisements have led people to believe it is relatively harmless (stock)
The trend took the life of Jacob Howard Stevens of Greenfield, Ohio, who died after taking 12 to 14 pills – one to two is a typical dose – which immediately caused seizures. The overdose left him brain-dead.
In May 2020, Cook Children’s Hospital in Fort Worth, Texas, issued a public warning about the trend after three teens were treated there for Benadryl overdose.
Each of these patients said they got the idea from videos on TikTok that claimed users could get high and hallucinate if they took a dozen or more of the allergy pills.
Based on research published a decade ago, long-term use of common anticholinergic medications like Benadryl may be linked to an increased risk of dementia.
A landmark 2015 study in JAMA Internal Medicine by American researchers followed more than 3,400 older adults for seven years.
The study found that frequent users of diphenhydramine and other antihistamines faced a 54 percent higher risk of developing dementia and a 63 percent higher risk of Alzheimer’s disease compared to non-users.
The physicians behind the pressure to remove diphenhydramine from the market added that the drug, most commonly seen under the brand Benadryl, is the driving force behind thousands of hospitalizations every year, driving up health-related costs nationwide.
These costs include emergency department visits, inpatient admissions, and physician office visits as well as indirect costs, such as decreased workplace and school productivity.
The researchers concluded that removing diphenhydramine from store shelves would protect patients and save the healthcare system money spent treating its side effects. They argued that the substantial public health benefit outweighs the minor inconvenience of limiting choice (stock)
A 10-year review of poison center data published last year in the journal Pediatrics revealed a sharp and alarming 87 percent increase in intentional overdoses of diphenhydramine among children and teens, with the leading cause being suicidal intent, a category that more than doubled.
The study found that 90 percent of these cases required treatment at a hospital or clinic, with one in five admitted to critical care.
Newer antihistamines are formulated to target allergy symptoms without crossing the blood-brain barrier, greatly reducing the sedative effects common with drugs like Benadryl.
As a result, they are considered non-impairing and are preferred for use during work, school or driving.
The researchers added: ‘Patients would benefit and the health care system would save money on the expenditures to treat adverse events if oral diphenhydramine were removed from the OTC market.
‘Although requiring a prescription would limit patient choice for those who prefer diphenhydramine over second-generation antihistamines, we believe this impact is outweighed by the substantial public health benefits. The consequence of maintaining the status quo is no longer acceptable.’
