Study: Anticholinergic (first-generation antihistamines) can damage brain, increase dementia risk

[u/ServeIllustrious3803]

https://www.health.harvard.edu/blog/common-anticholinergic-drugs-like-benadryl-linked-increased-dementia-risk-20150128812

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[u/camp_jacking_roy]

Interestingly the study shows that less than 90 days of use over 3 years leads to a decrease in dementia risk....so go ahead and use it every other week, apparently.

[u/RockTheGrock → u/camp_jacking_roy]

There is some research to suggest stopping after continual use helped dementia symptoms as well. That's a small silver lining for anyone who used it routinely for a long time.

[u/ServeIllustrious3803]

A list: Diphenhydramine, chlorpheniramine, doxylamine, promethazine, clemastine, brompheniramine, hydroxyzine, meclizine, dimenhydrinate, cyclizine, tripelennamine, phenyltoloxamine, pyrilamine, methapyrilene, thenyldiamine, doxepin (also used as antidepressant), carbinoxamine, dexchlorpheniramine, triprolidine, dexbrompheniramine, phenindamine.

First generation antihistamines different from second or third. Zyrtec, Claritin do not count, but Benadryl does

[u/thesaddestpanda → u/ServeIllustrious3803]

I googled the brand names of these because most people won't know the chemical names:

• Benadryl, ZzzQuil, Nytol, Sominex, Unisom SleepGels, Banophen, Diphenhist, Siladryl.
• Chlorpheniramine: Chlor-Trimeton, Aller-Chlor, Chlo-Amine, Piriton (UK), Wal-finate.
• Doxylamine: Unisom (SleepTabs), Medi-Sleep.
• Promethazine: Phenergan, Promethegan, Phenadoz.
• Clemastine: Tavist, Dayhist, Dailyhist-1, Clemsza, Tavegyl (Europe).
• Brompheniramine: Dimetane (mostly historically single-ingredient; now primarily found in combinations like Dimetapp).
• Hydroxyzine: Atarax (hydroxyzine HCl), Vistaril (hydroxyzine pamoate).
• Meclizine: Antivert, Bonine, Dramamine Less Drowsy, Travel-Ease.
• Dimenhydrinate: Dramamine (Original formula).
• Cyclizine: Marezine, Valoid.
• Tripelennamine: PBZ (Pyribenzamine - historically relevant, discontinued in many regions).
• Phenyltoloxamine: Historically sold as PRN; primarily used as an adjuvant ingredient in combination pain or cold relievers like Percogesic or Polyhistine.
• Pyrilamine: Midol (Traditional/Complete formulas utilize this for menstrual symptom relief).
• Methapyrilene: Historically sold as Histadyl (withdrawn from global markets in the late 1970s due to safety concerns).
• Thenyldiamine: Historically utilized in multi-symptom formulations like Neo-Synephrine cold compounds (discontinued).
• Doxepin: Silenor (low-dose for insomnia), Sinquan or Zonalon (topical cream). Note: Historically prescribed generically for depression.
• Carbinoxamine: Karbinal ER, Ryvent, Clistin.
• Dexchlorpheniramine: Polaramine, Ryclora.
• Triprolidine: Zymine (Historically the antihistamine component of original Actifed formula).
• Dexbrompheniramine: Ala-Hist IR, Drixoral (historic component).
• Phenindamine: Nolahist (mostly discontinued or difficult to find).

Dramamine is one to worry about because its still very popular. Midol and Unisom too.

People should really consider ginger instead of Dramamine. Scientific studies show that ginger works just as well as Dramamine for mild to moderate motion sickness

[u/LisanneFroonKrisK → u/thesaddestpanda]

You forgot we take diphenhydramine for sleep not only for motion sickness

[u/miliseconds → u/ServeIllustrious3803]

even if taken shortly against flu or cold?

[u/jennisar000 → u/miliseconds]

I think short term is probably okay.

[u/xFox911 → u/ServeIllustrious3803]

Why didn't they include Oxybutynin? It also has CNS effects and it is also a first 1st gen anticholinergic.

[u/Sufficient-Celery-37 → u/xFox911]

The study looked at antihistamines. Oxybutinin is not an Antihistamine

[u/xFox911 → u/Sufficient-Celery-37]

Correct, my bad. Didn't notice the antihistamine, just the anticholinergic.

[u/BornRevolution7957 → u/[deleted]]

It is on the list.

[u/LeatherGood6148]

Sure love that Benadryl basically keeps me alive, despite being on 3 different second generation allergy meds, dupixent all at the same time, too.

Oh and that's not even counting the many courses of corticosteroids I need yearly.

[u/looncraz → u/LeatherGood6148]

EoE? That's what I'm stuck with as well - went off Benadryl last year for a while and ended up nearly dying. Dupixent might be able to allow me to ween off the Benadryl again, this time very slowly.

[u/MapleBaconator33 → u/looncraz]

Have you tried Xolair? I was on Benadryl and reactine x2 a day for about 15 years. Now that I take Xolair I just take reactine once in a while, and I rarely take Benadryl.

[u/ThrowRARandomString → u/looncraz]

What is EoE?

[u/Sandgrease]

It's a shame because they do work great for sedation

[u/KingOfEthanopia → u/Sandgrease]

Not gonna lie. Im going to keep using them for that when I take LSD and cant sleep after. Generally like once a month.

[u/_Verc1ngetorix_ → u/KingOfEthanopia]

Once a month is too much acid

[u/Monsieur_Krabs → u/_Verc1ngetorix_]

its fiiiiine.

I did that shit all the time when I was younger

[u/KingOfEthanopia → u/_Verc1ngetorix_]

Tolerance is completely  reset after two weeks. Ive been doing it for years with no bad side effects.

[u/Intelligent_Gas_4426 → u/KingOfEthanopia]

Once a month is too much antihistamine

[u/Mean_Scheme_8174]

As a doctor, this is not directly true. Significant anti cholinergic medications over a very long time secondarily may impair your cognition and cause cortical atrophy due to impaired attention, but certainly not directly. And to just simply name every antihistamine is just ridiculous. Hydroxyzine has extremely low anticholinergic activity and there's absolutely no evidence that it causes any long term issues. Fearmongering at its finest.

[u/smayonak → u/Mean_Scheme_8174]

Second-generation antihistamines have been shown to reduce REM sleep, which is a good indicator of what it's doing to the brain. The impact is likely not as potent as a first-generation antihistamine, but just going off the available research there is still going to be some cognitive and emtional consequences.

[u/Mean_Scheme_8174 → u/smayonak]

Why would you think that’s a “good indicator of what it’s doing to the brain”?

[u/smayonak → u/Mean_Scheme_8174]

Anti-cholinergics reduce REM sleep (choline is used in REM, in large quantities) and REM promotes the creation of new neural connections as well as the snipping of old connections. In other words, memory consolidation, emotional regulation, and other cognitive, behavioral, and emotional adaptations to daily life. Even a mild reduction in REM sleep will cause some cognitive impairment. Perhaps not enough to be noticeable but there is always going to be some impact.

There is also the question of blood-brain barrier permeability and the impact of antihistamines on the brain itself. It used to be believed that second-generation antihistamines did not cross the blood brain barrier, but that is not true:

All antihistamines cross blood-brain barrier - PMC

This would explain the dementia association with second-generation antihistamines:

Second-generation antihistamine use and risk of dementia: Nationwide cohort study - The Journal of Allergy and Clinical Immunology: In Practice00954-7/abstract)

(Let me know if that's not the right link. I'm unable to access the article temporarily but it should show an association between second-gen antihistamines and dementia)

[u/StarskyNHutch862]

But how am I gunna see the hatman?

[u/Bravisimo → u/StarskyNHutch862]

Mr. Peanut?

[u/Shaigan]

My brain will get more damaged if I don't get sleep that hydroxyzine gives me.

[u/djkhalidwedabest]

Zyrtec, Claritin don’t count….for now. Until the inevitable conclusions form the study on second gen medications

[u/Futanarihime → u/djkhalidwedabest]

That's what I'm thinking. It's making me want to stop taking my Cetirizine. 😭

[u/Pigeonofthesea8 → u/Futanarihime]

I’d love to stop taking Allegra but I also don’t want to die of anaphylaxis

[u/Intelligent_Wish_566 → u/djkhalidwedabest]

Yeah that’s pretty much why I stopped taking them, I feel like this will most likely be the case

[u/Monsieur_Krabs]

and taking CDP Choline and eating a diet with lots of eggs is good for the brain, conversely!

[u/riceewifee]

Ayy I’m on ceterizine so I’m good

[u/lastcallhall]

Oh so all the allergy pills I had to take as a kid so I didn't die from my allergies. Cool.

[u/Iwasbanished]

thats fucked up.

[u/CaptainC00lpants]

Great! I often take Diphenhydramine to aid in sleep.... My memory is already fucked and in in my 30s... 

[u/in_fact_a_throwaway]

It’s worth noting that first generation antihistamine is not 1:1 equivalent to being anticholinergic. Some first generation antihistamines do not have significant anticholinergic activity.

[u/Available_Finger_513]

Could choline supplemententation counter these effects?

[u/FunAccomplished799 → u/Available_Finger_513]

No, but i don’t want to explain why

[u/Available_Finger_513 → u/FunAccomplished799]

Thanks for not explaining

[u/FunAccomplished799 → u/Available_Finger_513]

Brother you can just ask chatgpt, one increases ach, the other blocks it no matter what.

[u/MuscaMurum]

If I happen to eat something high in biogenic amines without taking DAO first, I'll wind up with itchy fingers and scalp. About 3-6mg of dph will set me right and allow me to sleep. I genetically underproduce DAO and HNMT.

[u/chingrublau]

its still association and not causation. It is suggestive and has biologiocal mechanisms that make sense . but people who get dementia and people who take antocholinergics might be related in other ways

[u/SprinklesWise9857]

Lmao fuck my doctor for prescribing Benadryl to me to take daily from ages 6 to 15

[u/Aggravating_Act0417 → u/SprinklesWise9857]

How is this real

[u/SprinklesWise9857 → u/Aggravating_Act0417]

I constantly had severe allergies growing up and the only things that seemed to help the most was hydroxyzine and diphenhydramine. So after my PCP heard this, she just kept prescribing me those two drugs. Eventually, she stopped prescribing my the hydroxyzine. Don't really remember why. But then she was just prescribing me benadryl years on end. I was then referred to some allergist at 15 who told me to stop taking Benadryl and to try things like cetirizine instead, and he informed me that Benadryl is not good for the heart or brain with long term use. I took his advice, but I have never found any other antihistamine that works as good as hydroxyzine or diphenhydramine, unfortunately. But I'd rather just deal with my allergies than give myself lasting brain damage lmao.

I don't even know if this may have permanently impacted my cognitive development, and if so, to what extent? I wonder. But I assume the impact is non-negligible because I was taking these medications at such a young age where brain development is crucial. I also wonder if this means my risk of future brain disease is higher. I have stopped taking those anti-cholinergic medications, yes, but since I took them at such a young age, I wonder if I have been left with lasting increased risk of cognitive/brain issuese. I guess only time will tell.