For generations, Benadryl (diphenhydramine) has been the go-to allergy medication. It is the pink pill that sits in your grandma’s medicine cabinet, the quick fix for sneezing, a sudden rash, or to fall asleep. However, as our understanding of allergies and medications has evolved, it has become clear that it’s time for most people to move on from Benadryl.
A quick disclaimer: I am not your doctor, and this should not be considered direct medical advice. Please discuss any specific questions with your personal physician.
Benadryl is known as a first-generation antihistamine because it was one of the earliest antihistamine medications invented back in the 1940s. Its main mechanism of action is to block histamine, which is released during allergic reactions.
However, histamine has other functions such as helping you stay awake, and Benadryl can easily get into your brain to make you feel sleepy. The medication can linger in your body and cause sleepiness for many hours. That is why the FAA does not allow pilots to fly for 60 hours after taking Benadryl. It also can impair your driving performance.
While many people may feel sleepy after taking Benadryl, approximately 10 to 15 percent of children may experience the opposite side effects known as “paradoxical excitation”. Instead of sedation, people like these children will experience agitation, restlessness, hyperactivity, insomnia and/or irritability.
This may be due to some people having the ability to metabolize the medication more quickly. This leads to the accumulation of molecules that are more excitatory.
Risks and Why Not a Sleep Aid
Benadryl is not just an antihistamine, but it also has anticholinergic properties. This means that it can block the neurotransmitter acetylcholine in the brain, which is an important chemical that is involved in memory and learning functions. There is some potential concern that chronic use of anticholinergic medications may increase the risk of developing dementia. More studies are needed to understand the potential risk, however.
Also, if you have seen products such as ZzzQuil that are used as sleep aids, they often contain diphenhydramine as their active ingredient. While the medication can help people fall asleep faster, it does not necessarily improve your sleep quality.
People who take Benadryl for sleep may have a significant increase in REM latency. That is the time it takes from falling asleep to your first period of rapid eye movement sleep (REM). This means that there is less total REM during a sleep session, causing reduced restorative sleep. Therefore, Benadryl should not be used as a sleep aid on a regular basis.
Benadryl’s Quickest? Not So Fast
Because Benadryl has become a household name, it has the reputation of working more quickly than the newer second-generation antihistamines. The newer medications include Claritin (loratadine), Allegra (fexofenadine), Zyrtec (cetirizine), and Xyzal (levocetirizine). However, this turns out to be a myth.
As an example, there is a study titled “Comparison of Cetirizine to Diphenhydramine in the Treatment of Acute Food Allergic Reactions” that was published in Pediatrics in 2011. This randomized, double-blind study compared Zyrtec (cetirizine) and Benadryl (diphenhydramine) in treating allergic reactions during oral food challenges in children aged 3 to 19 years.
The findings indicated that Zyrtec was as effective as Benadryl in managing allergic symptoms, with the added benefit of causing less sedation. The time it takes for Zyrtec and Benadryl to work are both roughly 15 to 30 minutes.
Also, second-generation antihistamines have significantly fewer side effects compared to Benadryl or other first-generation antihistamines. The newer medications do not generally have anticholinergic side effects. Overdosing on second-generation antihistamines is highly unlikely.
However, with Benadryl, there is a concern about toxicity. There was a “Benadryl challenge” that was ongoing in 2020, which lead the FDA to warn people against taking high doses of Benadryl.
When it comes to food allergies, I must stress that epinephrine is the only first-line medication for treating a severe food-allergic reaction (or anaphylaxis). With a mild food reaction, say hives or itching, your doctor may say an antihistamine is enough. But here again, allergists prefer second-generation antihistamines to Benadryl.
However, if you or your food-allergic child start experiencing symptoms involving more than one body system (skin, gastrointestinal, respiratory, cardiac), please don’t hesitate. Then it’s time for the epinephrine.
Rethink Benadryl: Speak to Your MD
Now with Benadryl, are there exceptions? Sure. For example, in an emergency room setting, people may not be able to take medications by mouth and need an intravenous route. In that case, Benadryl is usually the option because second-generation antihistamines in an intravenous formulation are usually not available. Also, this decision should be made between you and your doctor.
So why is Benadryl still so popular? It’s partly habit, partly marketing, and partly cost. This medication has been around a long time, so many people may assume that Benadryl is safe and effective. However, our understanding of these medications has changed.
If you are reaching for Benadryl, then it is time to rethink. For most people, the benefits of second-generation antihistamines are similar to Benadryl and have fewer side effects. Talk with your doctor about newer antihistamines that are safer.
This post is meant for general educational purposes only and raising awareness for both patients and healthcare professionals.
Dr. Zachary Rubin, a prolific communicator on allergy and medical topics, is double board-certified in allergy/immunology and in pediatrics. Follow his widely read reports on his Substack account and see his videos on Instagram or TikTok.
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