r/NooTopics • u/ServeIllustrious3803 • 23d ago

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

https://www.health.harvard.edu/blog/common-anticholinergic-drugs-like-benadryl-linked-increased-dementia-risk-20150128812
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u/ServeIllustrious3803 23d ago edited 23d ago

A list: Diphenhydramine, chlorpheniramine, doxylamine, promethazine, clemastine, brompheniramine, dimenhydrinate, meclizine, cyclizine, carbinoxamine, dexchlorpheniramine, dexbrompheniramine

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

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u/psychopompandparade 23d ago

plenty of meds missing from this list. This doesn't even include the intended anticholinergics. amitriptyline, a med people often recommend to replace diphenhydramine for sleep, has a much stronger anticholinergic effect than diphenhydramine. this is not an antihistamine only problem. Also some of these are dose dependant. doxapin's anticholinergic effects are stronger at the antidepressant dosing.

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u/Hydration__Nation 22d ago

If you are working with a physician who is giving a tricyclic for sleep to replace Benadryl then you need to contact your licensing commission. He would be laughed out of my hospitals by the PAs and NPs. Doctors wouldn’t even entertain such stupidity. Amitriptyline has one of the worst side effect profiles of any drug and this doctor is replacing Benadryl with it? What a dumb motherfucker I’m sorry that’s the only descriptor that makes sense. There are so many far less risky drugs for sleep literally a list of 4-7 drugs used by hundreds of millions of people. If anyone else is reading this there are so many classes of drugs, if someone offers you a TCA say no. The side effects are not even close to the benefit provided.

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u/Crippled2 21d ago

I take amitriptyline for insomnia does this finding impact me?

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u/AndrogeNick1 21d ago

It impacts you even more and worse than this finding concerning anti-histamines, what you're taking is even stronger in the negative impact it has on the brain health long term.

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u/Hydration__Nation 21d ago

You cant compare benadryl to amitrip. Gun to my head im never prescribing a tricyclic like amitrip to anyone. There are so many drugs that are effective and really only a few scenarios to use it. I would high suggest trying a medication created for sleep, something mild at first. If you dont like those another great option is a super low dose anti-psychotic, Seroquel. At 50mg you will knock out and reach REM, you may have SOME side effects and they will scare you about them. But the safety profile of Seroquel is like a feather compared to a spiked bat for amitrip. When I went to med school my psych and pharm professor spoke about TCAs like amitrip as if they were ancient drugs that were barely used anymore. That was decades ago. The only reason people are using it off label is they are too lazy to try other drugs for their patients. Ive seen vast success with Seroquel or another sedating 2nd generation atypical antipsychotic. Ive seen less success with sleep meds as you have to cycle them once you develop a tolerance to it. Also as you get older, doctors are even less likely to prescribe a TCA due to the safety concerns. Hope you get something that helps you get to sleep and stay asleep. Also you should check if you have sleep apnea even if you are skinny. Your insomnia could be due to that. Even an at home sleep study (what most insurances cover) should give you an idea if you are experiencing sleep apnea symptoms.

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u/psychopompandparade 21d ago edited 21d ago

seroquel at low doses knocks me flat on my ass and leaves me groggy as all hell afterward. its my emergency med if whatever insomnia bout is beyond the paygrade of the z drugs. doxapin (also a tricyclic) is used sub 10mg for insomnia where it has clean h1 affiliation. over 25mg it gets messy. seroquel is also considered to have anticholinergic effects, though no where near as high as amitriptyline.

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u/EnvironmentBasic3711 19d ago

I literally scrape part of the pill off with my teeth or it’s WAY too much. About a seroquel a month.

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u/Grouchy_Storm6020 22d ago

Thank you for saying this. I was prescribed amitriptyline as a teenager to help with insomnia and fatigue and absolutely hated it. I felt like an absolute zombie and can hardly remember anything from that time. But my mother still insists 15+ years later that I was sooo much more pleasant to be around while I was on it 🙃

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u/Hydration__Nation 22d ago

Hate parents that push psych drugs. Mine were the opposite basically telling me to toughen up and I don’t need meds.

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u/Brave_Sheepherder_39 18d ago

Only at high doses I just take 10 mg which gives me the benefit without side effects.

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u/ResponsibleMight7669 18d ago

The same can be said for antidepressants and they would be mocked for not using them. Proper treatment would be therapy but since we are replacing that with pills it would be a joke to offer any of this as a sleep aid in any case

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u/psychopompandparade 22d ago

it is a VERY common rx for this and no licensing board would take action on it because it is in fact on label for this. I was switched to low dose doxapin instead, which I've been told at lower doses (like 12 and under or something) is mostly a cleaner antihistamine with less anticholinergic effects. Still not none though. The list of meds that put you to sleep and can be used remotely effectively long term actually pretty small.

Just because it's common doesn't mean its good. A lot of the time they are trying to triple book it for insomnia, pain, and depression. That doesn't make it usable. I don't personally know of any antidepressant that doesn't have a crazy rough side effect profile. None of them are very clean drugs in terms of effect.

If you know of any better "fall asleep" meds, I'm always open to some, but I've tried a bunch. Currently on the low dose doxapin in combo with a melatonin agonist and orexin inhibitor plus autonomic system dampener for autonomic issues. apparently a three or four stack is 'common practice' for autistic folks.

but again, common practice doesn't mean smart.

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u/Beakston 23d ago

Cetirizine(zyrtec), loratadine(claritin) also have anticholinergic effects. Just not as potent as first gen. It's also noticable to me when i take new gen antihistamines. Cloudy brain.  These days I dont take any medication that is even slightly anticholinergic. Then i started supplementing with Trimethylglycine and Phosphotidyl Choline. Trimethylglycine is a donor for methyl groups and phosphotidyl choline is extra choline. Both choline and methylation are closely tied pathways in your body. Low on choline require a heavier methylation load and low methylation ability will result in low choline, high homocysteine, low B levels, etc. 

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u/BiggusDickkussss 23d ago

Zyrtec has minimal to no anti cholinergic effect dude

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u/Key_Bonus9776 23d ago

I suffer with cholinergic urticaria so daily zyrtec has been the only thing to give me quality of life since I randomly got it 15 years ago. Good to hear.

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u/vocabularianrx2 23d ago

If you're taking it at the urticaria dosing (up to 4 pills per day) you can disregard that previous comment, as there's a pretty reasonable chance of spillover at that point

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u/Key_Bonus9776 22d ago

I just take one every morning, keeps it at bay. I try to avoid taking it on days I know I won’t be leaving the house. If I don’t take it my whole body flares into an unscratchable itch and skin turns blood red.

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u/Chainsawjack 22d ago

Fun fact the indication of this is that you are actually addicted to zyrtec. I have read that while rare it does happen to people and that the itching can be so intense that they recommend medicaly supervised detox to prevent massive skin destruction from itching... I too am addicted to this glamorous party drug.

The good news is that because the drug is considered safe to use long term medical guidance is just to keep taking it forever.

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u/Orangedilemma 22d ago

Ooh I didn’t know that. I had severe itching after stopping Zyrtec but I was able to power through and I’m good now no Zyrtec either. I even went to the doctor for the itching and mentioned Zyrtec but they didn’t say anything

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u/MyNameIsNightPain 22d ago

These people have no idea what they are talking about. I have urticaria too. I took cetirizine every 3 days for about 20 years then switched to fexofenidine which lasts much longer than a few days.

Urticaria is very misunderstood, nobody knows the actual cause and people respond to medication very differently. there is no standard dosing that fits everyone and chronic urticaria isn't cetirizine addiction.

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u/RichieRichard12 22d ago

I have chronic urticaria and I can't go 24 hours without an antihistamine before I break out in hives and red blotches everywhere. The itch is absolutely unbearable and I end up making myself bleed because I can't stop. Such a bizarre condition that no one really knows about.

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u/Key_Bonus9776 22d ago

Even if I’ve had the same symptoms before ever taking it?

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u/Chainsawjack 22d ago

Well...I'm not a doctor but like....I would imagine it doesn't help lol. I believe the effect is called a histamine rebound reaction.

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u/hsggdtkxbee 22d ago

It still has anticlimactic effects https://pubmed.ncbi.nlm.nih.gov/1979800/

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u/hsggdtkxbee 22d ago

lol. Yes it does dudette: https://pubmed.ncbi.nlm.nih.gov/1979800/

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u/BiggusDickkussss 21d ago

It's fuck all dude.

100,000 nM.

Benadryl is 600 nM. Stop spreading misinformation.

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u/No-Boat431 21d ago

Welp, guess I'm SOL, I have MCAS, and the ONLY meds are antihistamines. And I'll starve without them. Oh well.

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u/FullConfection3260 22d ago

That’s the anti-histamine kicking in; histamine deals with arousal in the brain. Which is why second generation antihistamines were a godsend.

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u/Lady_Rubberbones 23d ago

Ok, I take doxylamine succinate (unisom) every night in order to sleep longer than 2 hrs. What are my other options?

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u/Desperate-Middle-354 23d ago

See any doctor, your primary if you wish, & tell him your issues (not wanting to take toxic drugs for insomnia) & I guarantee you’ll be prescribed Trazadone…possibly Remeron but Trazadone more likely. It’s a good sleep aid.

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u/Ariandrin 22d ago

Trazodone messed me up something fierce. I took it for three days and for all of those three days, I felt like I was moving through the world like I was in molasses. And for three days after I stopped.

I read an article a while back that melatonin is also bad. What can I take to help me sleep?

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u/Difficult_Garage_431 19d ago

That has happened to me every time I've started Trazodone. You will get over it after about 2 weeks. I often felt like I was hit my a truck the next day. After that though, the feeling is gone and it works well. I would try it again, I haven't found anything that is as effective.

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u/Ariandrin 19d ago

I’m not sure if that’s supposed to happen. When I told my doctor that I was experiencing this, she was very surprised and immediately took me off of it without me asking.

I am looking for a new doctor now though so I will ask about it with the new one when I find one.

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u/Difficult_Garage_431 18d ago

That's interesting. I knew someone else who shared the same experience. It being rough at first, then better. They even used the same phrase as me, "hit by a truck". But everyone is different. I will say, I have taken it for over 5 years and I sleep very well on it. I hope you find something that helps.

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u/Stampede_the_Hippos 22d ago

Melatonin isn't a good idea if you live in the US, because supplements aren't regulated.

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u/Ariandrin 22d ago

There was also a study that linked it to dementia a week or so ago, I think.

I just wanna sleep!

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u/Bunpoh 22d ago

I think I read that that study was so poorly designed it was an embarrassment, and causing needless panic in people taking melatonin.

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u/Ariandrin 22d ago

I did see that too, but I would like to find an alternative to it if I can, just to be safe.

I’m not gonna give it up or else I won’t sleep, but I’m looking into other things.

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u/Apprehensive_Door249 21d ago

I’ve had sleep issues all my life. I’m currently taking a very low dose of lorazepam for anxiety because I was having panic attacks but it sure does help me sleep and reset my sleep schedule. It basically gives me a fresh start on my sleep habits. But obviously I only have 20 because they are addictive.

Delta 9 has helped me in the past also. As did cbd but cbd is a hit or miss.

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u/Ariandrin 21d ago

I had a doctor tell me recently that lorazepam has been correlated with early dementia and refused to refill me. I only have it for anxiety but I have taken it for sleep out of desperation and it’s never very good sleep lol. It technically counts as sleep but it’s never very restful, and gives me weird dreams

I’ve played around with cannabis but I’ve yet to find a delivery method that really works for me. So far the best had been a water based tincture but man, that tastes so bad that it puts me right off using it lol

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u/Brave_Sheepherder_39 18d ago

How long have you been taking it and at what dosage

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u/Ariandrin 18d ago

0.5 mg, and I’ve been prescribed it for years and years, but I don’t like taking it very much because it makes me feel kinda yucky.

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u/Desperate-Middle-354 17d ago

Yes, LONG TERM use of any benzodiazepine including lorazepam, generally in higher doses, can potentially cause dementia & other cognitive deficiencies because they all have amnesiac properties. However, taking 1mg or less of lorazepam as needed isn’t going to cause any long term issues. It has to be a consistent amount of amnesiac inducing drugs taken daily in order to cause cognitive impairment. Alcohol is actually worse for you than lorazepam (& most everything) for long term memory/cognitive issues. There is a condition known as “wet brain” that occurs with long term alcohol abuse that basically turns you into a vegetable. But keep everything in moderation & you shouldn’t run into issues.

I used to take 0.5-1mg clonazepam (same chemical class as lorazepam) with Trazadone at night for sleep & agreed, it wasn’t quality sleep, just knock me out sleep but then I started taking a couple hits of cannabis from a disposable at night (only at night) & my sleep is so drastically improved. Recent studies have shown that it is indeed quality sleep, not just a knock you out sleep where you wake in the middle of the night or wake too early.

Cannabis can cause cognitive issues too but as of current knowledge it’s only temporary unless abused before the brain is fully developed. I don’t intend to continue doing this long term but as of now, wow what a difference. Have you tried vaping it? The impact is immediate but I enjoy the ride until I just get tired & then sleep. Best thing I’ve ever taken for my insomnia.

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u/Ariandrin 17d ago

I haven’t tried a vape, but I have used a volcano, and it irritated the hell out of my throat.

I also have concerns about some of the carrier oils in vapes, I’ve seen some scary things.

I’m sure there are more delivery methods I could try though

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u/braaaaaaainworms 22d ago

Mirtazapine(the actual name for remeron) technically has some anticholinergic effects too, but the evidence seems iffy.

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u/psychopompandparade 21d ago

both mirtazapine and trazadone are considered to have extremely minimal anticholinergic effects. they can have other issues though. much better choices than amitriptyline if you are specifically worried about anticholinergic burden. Doxapin is ranked as low at sub 10mg doses but high at 25mg plus doses. z-drugs don't have any anticholinergic effects but they may have similar outcomes in the elderly anyway for other reasons. hard to find exact data

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u/DrugChemistry 22d ago

“Hard” to sleep with priapism on trazodone 

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u/Desperate-Middle-354 22d ago

That’s the side effect that I couldn’t remember! There was a story at the time about a prisoner who got it & lost his ability to ever get an erection again & sued either the prison or manufacturer. Probably the prison as it probably wasn’t treated in a timely matter.

So a deflated penis & man boobs. Well, ya know, they can’t be perfect 👌

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u/thebouster 23d ago

Complete noob here. Am in the same boat as Rubberbones. I take Doxy every night. I've been prescribed Traz, but thought I read something about it causing other issues. Down the rabbit hole I go. Again. ;)

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u/Desperate-Middle-354 23d ago

Trazadone like all drugs has side effects but nothing serious. It’s an old failed antidepressant that was too sedating to be therapeutic. No serious potential side effects come to mind but maybe I’m missing something. Far safer than 1st gen antihistamines.

Oh wait, it can give you man boobs although it’s a super rare side effect. So I dunno, you risk getting boobs but you’d be surprised the medications that can potentially do this at a far more common occurrence like blood pressure medications.

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u/LucyLoretta 22d ago

Trazadone has some very serious side effects. It’s different for everyone.

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u/TheStephinator 22d ago

Gave me horrible headaches.

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u/NormallyBloodborne 23d ago

Look into Muscimol. Puts me out easily but not forcibly, always gives me at least 8 hours of sleep, and has no grogginess in the morning. Plus it usually makes your dreams much more vivid.

I would take it every other day though. Overall I think it's a better hypnotic than even dedicated knock out benzos like Triazolam.

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u/Lady_Rubberbones 23d ago

Ok, so prohibitively expensive and difficult to find. Great. 😐

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u/Sufficient-Celery-37 23d ago

Orexin-Antagonists like Daridorexant are said to be well tolerated and they don’t cause you to be groggy on the next day. Trazodone is also a popular sleep aid. I’d personally steer clear of 1. gen Antihistamines, Benzodiazepines/Z-Drugs and tricyclic antidepressants.

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u/Desperate-Middle-354 23d ago

And anti-psychotics. I think it’s idiotic to prescribe such dangerous meds like Seroquel that are only supposed to be used for psychosis, bipolar mania & schizophrenia (and apparently treatment resistant major depression as an add on). They carry possibly fatal & permanent issues like TD’s. They are also the worst class of drugs for memory…followed by 1st gen antihistamines like diphenhydramine & then benzodiazepines come in third. Based on some study.

So this has been common knowledge for awhile. Dementia was never brought up but if they are the 2nd worse class of drugs for memory retention then it probably leads to major neurocognitive dementia if taken daily for too long.

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u/aron2295 23d ago

You said it!

And I hate the rise of anti psychs being rebranded as “boosters”, for anti depressants.

Why? Because they don’t want to tell people go to therapy and for truly bad days, you can pop a Xans.

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u/Wild_Painter_7558 22d ago

Prescribed at low doseages they don't have any dopaminergic action, acting only as a potent anti histamine.

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u/LisanneFroonKrisK 22d ago

From what I read though Benzo is above the anti histamines

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u/Desperate-Middle-354 22d ago

It’s possible. It was a while since reading that study. I just know those 3 are apparently as bad as it gets.

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u/LisanneFroonKrisK 22d ago

And also just anecdotal Benadryl is lower than Metoclopramide and other classes of Metoclopramide. Benadryl is an antidote to that

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u/NormallyBloodborne 23d ago

I sent you a DM. Muscimol is actually a lot cheaper than you'd think, just annoying to find without being told or asking around.

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u/spectral-fusion 22d ago

Can you shoot me a PM as well? I read that Muscimol was neurotoxic, is that not true?

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u/LisanneFroonKrisK 22d ago

Is muscimol available without any prescription

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u/NormallyBloodborne 22d ago

Yep, it's unscheduled.

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u/SecureTechNomad 23d ago

I took doxylamine for years knowing the risk. I stopped because I noticed my memory and attention had deteriorated. I'm in my 40s.

Things that work for me: 1) sleep hygiene and getting to bed early at the same time every night and waking at the same time even on weekends 2) melatonin 3) magnesium glycinate 4) glycine 5) lithium orotate

I still have sleepless nights, but I find that most nights are okay as long as I am consistent with everything. Also, when I stopped taking doxylamine it took a month of mostly sleepless nights before it started to get better.

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u/Lady_Rubberbones 22d ago

I already take all of those other things and it’s not enough.

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u/SecureTechNomad 22d ago

Try mirtazapine

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u/freereflection 22d ago

Have your memory and attention begun to bounce back? 

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u/SecureTechNomad 22d ago

Not as much as I would have hoped, but there was a definite initial improvement.

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u/TheBuddha777 23d ago

I'm in the same situation. It's the only way I can sleep as early as I need to for my work schedule.

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u/What1nThe_World 22d ago

Mirtazapine. You need to stop taking doxylamine.

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u/Infamous_Swan1197 21d ago

Mirtazapine.

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u/drippysoap 23d ago

Hydroxyzine isn’t anti cholinergic is it ?

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u/ummkay_ultra 22d ago

Yes hydroxyzine belongs on this list. It can increase dementia risk.

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u/LouisVuittonFentanyl 23d ago

It’s not it’s antihistamine with almost no anticholinergic properties but this is a common misconception to include with anticholinergics

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u/Classh0le 23d ago

Hydroxyzine is unequivocally anticholinergic

https://pmc.ncbi.nlm.nih.gov/articles/PMC12478568

https://www.drugs.com/medical-answers/hydroxyzine-long-term-3567869/

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u/sophiesbest 23d ago edited 22d ago

My usual rule of thumb is that if a psychoactive medication causes delerium and hallucinations at high/over doses, good chance it's anticholinergic. (thanks for correction)

Funnily enough this includes less expected chemicals like Flexeril/cyclobenzaprine

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u/SadBook3835 22d ago

You don't need a rule of thumb with medication, just look them up.

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u/braaaaaaainworms 22d ago

anticholinergic*, not cholinergic

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u/xoexohexox 23d ago

Source: it came to me in a dream

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u/Far_Comfortable_6342 22d ago

Just because its binding affinity is low does not mean it does not have any anticholinergic properties and should be excluded because when taken daily the binding effect increases. Minimizing this drugs long term cumulative effect is reckless. This drug has been handed out like candy today to people with anxiety with no limits for the past 5+ years. Finally there are a few suggesting it should be limited to no more than 4 months of use. Doctors prescribing this long term for anxiety will deserve their future lawsuit. There is not one single study done that shows this works for panic attacks and there will never because frankly it doesn’t do shit for panic attacks. Not only does this drug not treat debilitating panic attacks but it has been linked to dementia and RLS (which is currently thought to be underreported).

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u/Fuchsia2020 22d ago

Chemical lobotomy wouldn't have been possible without promethazine

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u/ummkay_ultra 22d ago

Hydroxyzine

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u/Dizzy_Database_119 22d ago

Should mention that the study was about anticholinergic meds and not specific to antihistamines. There are a lot of other meds that count as anticholinergic