Why it is time to move on from Benadryl (for most people)
Why many allergists are moving away from this old drug...
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 clearer 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. Any specific questions should be discussed with your personal physician. This post is meant for general educational purposes only and raising awareness for both patients and healthcare professionals.
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 10-15% of children may experience the opposite side effects known as paradoxical excitation. Instead of sedation, some people 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, leading to the accumulation of molecules that are more excitatory.
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, which 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 chronically.
Because Benadryl has become a household name, it has the reputation of working more quickly than the newer second-generation antihistamines such as Claritin (loratadine), Allegra (fexofenadine), Zyrtec (cetirizine), and Xyzal (levocetirizine). However, this is now 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 acute 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 15-30 minutes.
Also, second-generation antihistamines have significantly less 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 are highly unlikely. However, there is a concern about Benadryl toxicity. There was a “Benadryl challenge” that was ongoing in 2020, which lead the FDA to warn people against taking high doses of Benadryl.
Now, 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 only 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 less side effects. Talk with your doctor about newer antihistamines that are safer.
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Pharma chemist here (and huge former Benadryl-taker due to growing up in the 70s/80s with massive poorly treated allergies and asthma). The research about Benadryl and Alzheimers is quite interesting, but I think it's raising a lot more questions than it answers right now. This is a correlative relationship and not a causative one (for now).
We have also been able to correlate high inflammatory markers with dementia/Alzheimer's. People with some chronic illnesses or allergies are likely to have chronically higher inflammatory markers as well. So it may not be Benadryl causing the Alzheimers, but the underlying inflammatory issue that inspires the Benadryl treatment.
To be fair, I do think Benadryl is a terrible idea for a sleep aid and I wish it wasn't sold as one.
But for allergies, I think it's too early to know for certain. If the newer antihistamines work for people, that's fantastic and ideal, but I don't want to scare people into thinking Benadryl is going to give them Alzheimer's.
Personally, I have found that Zyrtec & friends can work very well if my symptoms are mild. But sometimes they don't have any impact on more severe symptoms and I need Benadryl. (I am adding this not to start any arguments or provide medical advice, but to validate anyone who reads this and feels like something is "wrong" with them because they have similar experiences. I know I am not alone and it can be really concerning to feel like I'm doing something wrong by doing what I need to do to stay out of the hospital.)
Prior to retiring, I was the nurse educator for The Mast Cell Disease Society. Our medical advisory board members were several allergists and immunologists in the US and abroad. I was instructed to educate our patients exactly as you described Dr. Rubin. Benadryl was reserved for emergent situations that required IV (intravenous) administration of antihistamines. One of our board members recommended Claritin Reditabs, since they dissolve so quickly and don’t require water to take. We also advised patients they could take the less expensive generic version. I appreciate your education.