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PaperclipPerfector  10mo ago (text post)   3146 thread views

Small-Scale Question Sunday for December 31, 2023

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Antihistamines. Do they reduce IQ?

Yes. The sad thing about the majority of pharmaceuticals in use today is that they're blunt instruments, hammers substituted for scalpels. Histamine, while we're mostly accustomed to encountering its effects from annoyances like hives or allergies, also functions as a neurotransmitter in the brain. It happens to modulate arousal and awakening in the brain, which is why sedation is/was a common side effect of antihistamines (more so in the older ones).

https://pubmed.ncbi.nlm.nih.gov/10856168/#:~:text=In%20a%20recent%20comparative%20trial,memory%2C%20vigilance%2C%20and%20speed.

In a recent comparative trial, subjects who were treated with the first-generation agent diphenhydramine were found to have significant performance deficits on tests of divided attention, working memory, vigilance, and speed. By contrast, subjects who were treated with the second-generation antihistamine loratadine performed as well as subjects who were treated with placebo. The sedative effects of the first-generation agents persist well into the next day and thus can potentially interfere with daytime performance and safety even when taken the night before. It is therefore recommended that patients whose occupations require vigilance, divided attention, or concentration receive only second-generation antihistamines.

The second-generation antihistamines are classified as "non-sedating", which is more or less correct, even if a few of them do have mild sedative effect, at least they're much better in that regard than the OGs. Keep in mind you're not thinking your best when you've got a reason to take them, such as during allergies or a cold.

I don't see any suggestion that the effect persists indefinitely, at least not for acute use at recommended doses, and you can avoid the worst of it by getting the better ones from the non-sedating class.

Is daily cetirizine use significantly hazardous?

My memory says no, but I did look it up and there doesn't seem to be any claims of it being hazardous beyond the mild sedation itself.

Thanks!

Related followup: what is the safest OTC sleep aid? Thoughts on doxylamine (unisom)?

This really depends on what your use case is.

If you're worried I would go for some kind of antihistamine since even the non-benzo benzo derivatives have higher risks of death associated with them.

On the other hand, if you're driving to work I would be careful with the antihistamines. They really do make you drowsy in the morning, especially at the higher doses. The effect does go away and I've had no trouble performing at work after taking them but I almost crashed my car once... If you take PT, bike or get driven to work they're great imo.

Finally, I hope it goes without saying that sleeping aids really shouldn't be something one takes every day, for a whole host of reasons, and if you have to take one for extended periods you should really stay away from benzodiazepines and their derivates.

If you take PT, bike or get driven to work they're great imo.

with cycling it is fine only when you have cycleways separated from roads without real pedestrian/cycling traffic on them

falling under car while on bicycle is a poor idea

That is true to an extent but cycling by it's nature also keeps you awake and alert in a way that driving doesn't. The lingering effect isn't that strong and I've never been worried in the slightest or close to an accident when biking. In a car people start drifting off by just being regular tired.

Furthermore, it's not the high stress environment that is the highest risk imo, it's when you're in steady pace traffic.

In the end this is something one has to figure out for oneself and it depends on how one reacts to the medication and being careful is prudent. Smaller doses are advisable anyway and they significantly reduce risk and severity of morning drowsiness.

definitely makes sense, more than what I expected to be reasoning (that on bicycle hitting others will cause much lesser harm), thanks for clarifying

(I have quite limited experience with car driving)

You said safest, not the most effective, so I'm going to go with a glass of cold milk haha.

Truth be told, there isn't much in the way of good, almost perfectly safe choices, at least in OTC drugs that I'm aware of, and availability might well be in different in the States from what I'm used to. I could vaguely recommend l-theanine as a highly safe anxiolytic, even if it's not a sedative. Melatonin is highly dubious in terms of usefulness. But if you want to be knocked the fuck out, older antihistamines are your friend.

I don't have a particularly strong opinion on doxylamine beyond my theoretical knowledge, it's not the antihistamine used regularly where I hail from, but used in moderation? Doesn't seem all that bad. But it will almost certainly have the cognitive effects I mentioned above.

Just did some reading of actual studies. E.g. this meta-analysis from NCBI:

Research conducted among hospitalized older adults found that pharmacological (e.g., benzodiazepines) and non-pharmacological (e.g., diphenhydramine) medications resulted in an 18% and 22% respective increased rate of delirium among the sample.14 Also, research conducted among community-dwelling older adults found that non-pharmacological medication use was associated with lower cognitive function scores as compared to those not taking these components over a 10-year follow up period.15

Why should I find this plausible, rather than making the standard "correlation is not causation" point? Surely people with issues sleeping are in general less healthy, physically and/or psychologically. I don't see anything in there to indicate they controlled for anything.

Some references also seem to do nothing more than ask if people took any sleep aid, lumping together everything from melatonin (presumably very safe, maybe placebo) to daily benzos (clearly neither very safe nor a placebo).

Edit: I am bad at reading (maybe it's the doxylamine). They did control for things. But my question re causation stands. I feel like TheMotte is usually very skeptical, and I find myself surprised by the strength of multiple posters' convictions here.

while controlling for demographic covariates, including age (0= 65 up to 75 years of age; 1= 75 years of age and above), sex (0=male, 1=female), race (0=white, 1=non-white), and relationship status (0=widowed, single, or divorced, 1=living with partner or married). Third, we examined the relationship between sleep medication use and incident dementia while controlling for Model 2 demographic covariates and health conditions (0=no chronic conditions; 1=heart attack, 2=depression, 3=hypertension, 4=stroke, 5=diabetes). Depressive symptoms were measured using the Patient Health Questionnaire-2.34

Fascinating that you say melatonin is dubious in usefulness. I swear by my 300 micrograms a day (dosage at Scott's recommendation).

I've been taking Claritin (loratadine) but I still feel like I'm losing some bandwidth. I can't hold as many things on my mind as I usually do. Too bad it's either this or hives for now.

Levocetirizine is a non-sedating one that causes minimal cognitive effects, I'd recommend it. The paper I linked has examples of some others that couldn't be disentangled from placebo, so hopefully you find one that works for you.

Or you could go for a topical preparation? That should have fewer cognitive side effects.

(Original) Benadryl is also an anticholinergic, and "Anticholinergic use later in life is associated with an increased risk for cognitive decline and dementia among older people."

I don't recall reading about any indications of problems from other antihistamines, but then again I only happened across this one by chance, years ago; I'm not an MD or pharmacist. Many antihistamines have drowsiness as a side effect, and that always makes me a bit suspicious.

Many antihistamines have drowsiness as a side effect, and that always makes me a bit suspicious.

Is "causing drowsiness" inherently an indicator of long-term negative cognitive effects?

Inherently? Surely not. This is just a vague heuristic, and I'd be shocked if it was actually a universal rule. It just seems that there are some pathways to "make brain quiet down now" that don't do so perfectly gently, which a priori isn't too surprising. General anesthesia and alcohol are the two other examples that come readily to mind. So when I see a new drug that has that effect, and there's no safe explanation (like for melatonin) apparent, I wonder if it's doing so unsafely.

I don't worry too much though. I've had general anesthesia once, and I wouldn't hesitate to take Benadryl after an allergic reaction, because I doubt the costs outweigh the benefits, and I had a glass of wine with dinner tonight, because YOLO.

Is there evidence they do?

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