My goto anti-hayfever drugs are Loratadine and Cetrizine in generic non-branded packets for cost reasons. OP's article worried me because I regularly take one or both of them for two months straight over summer.
The article states that Loratadine is recommended as an alternative for the relief of allergies. The article didn't explicitly mention Cetirizine but I have done some research and came across another article from 2012 which does include Cetirizine in the same category as Loratadine:
I believe I am safe to continue using Cetirizine and thought some of you may have the same question. I am not an expert on these issues so if I'm mis-understood any of this please let me know.
The linked study (not OP's article) only mentions first generation antihistamines, and Cetrizine and Loratadine are both second-gen ("non-drowsy"). This study[1] alleges that Cetrizine does not have a cholinergic response associated with it (good), but that Loratadine did show anticholinergic activity (bad).
The OP article says:
> Those with allergies can take a second-generation antihistamine like loratadine (Claritin)
But perhaps Cetrizine is more safe, and we should not be taking Loratadine if we can avoid it. Thoughts, anybody?
The linked chart dated 2012 lists cetrizine and loratadine as "possible" anticholinergics. It appears they will equally put you at risk. So what are allergy sufferers alternatives? I'm dependent on loratadine and a little dismayed to just now learn of this even if the correlation is not clear.
Guess I'll just have to start eating a bunch of honey...
Same - just took a generic fexofenadine, in fact. Of course, 5 years ago, everybody thought diphenhydramine was safe, too.
But is there a "safe minimum frequency"? Generally, I try to avoid taking any medication more/longer than necessary, and my bottle of diphenhydramine is still mostly full after many years...
montelukast (sadly not OTC in the US) isn't known to have an anticholinergic effect, same with most nasal sprays afaik (with the exception of ipratropium bromide). i've had great success with montelukast+cetirizine+flonase.
(and ditto the other comment saying the honey thing is bogus - i eat a lot of local honey because it's tasty, but it makes no impact on my seasonal allergies.)
Bit of a thinking-outside-the-box suggestion here, but have you tried something like mindfulness? Allergy, inflammation and stress seem to be linked in some way, so changing your mindset might reduce the response that you are blocking with loratadine. I personally (in a totally unscientific way) think that low level stress acts like an amplifier for these sorts of conditions.
My wife who has very bad allergies has switched to a saline nasal rinse twice a day. It has eliminated the need for any allergy meds except on really exceptional days (which might simply require 3 rinses but that experiment hasn't been done yet.)
> ...“basically any cold medications that make you sleepy might contain anticholinergics, so stay away from drugs that make you sleepy.” NyQuil is an exception, he said. It makes people sleepy, but does not contain an anti-cholinergic. Still, “if your solution for a sleep problem is a pill, a quick fix, do you want that?” Any drug taken for a long time could come with problems.
Over the counter sleep medicines lose their effectiveness when taken regularly, so it people are less likely to do so (vs. taking such medicines for allergy relief).
Also NyQuil contains doxylamine [1], which is an anticholinergic, and is listed with the other problematic medicines [2].
I wonder why NyQuil is outside of quotes. Did a professor of medicine really make such an unbelievable mistake?
Let us not forget that this class of drugs (which includes diphenhydramine (Benadryl), scopolamine, and datura is called "deliriant".
From Wikipedia:
" The term was introduced by David F. Duncan and Robert S. Gold to distinguish these drugs from psychedelics and dissociatives, such as LSD and ketamine respectively, due to their primary effect of causing delirium, as opposed to the more lucid states produced by other hallucinogens (psychedelics and dissociatives)... The delirium produced is characterized by stupor, confusion, confabulation, and regression to "phantom" behaviors such as disrobing and plucking.[2] Other commonly reported behaviors include holding full conversations with imagined people, finishing a complex, multi-stage action (such as getting dressed) and then suddenly discovering one had not even begun yet, and being unable to recognize one's own reflection in a mirror."
This is the expected behavior for someone who consumes about 500-700mg of diphenhydramine at once (the dose suggested on the package is usually 50mg). Benadryl is probably the most powerful hallucinogen known; it distorts the senses far more than even some of the most notorious illegal drugs and the reasons for its continued over-the-counter legality might make for an interesting book. Obviously it has healthy uses, and many deliriants have long-established religious uses in North America. The Serpent and the Rainbow and Passage of Darkness: The Ethnobiology of the Haitian Zombie are two books that explain how anticholinergic drugs are what create real-life zombies.
>I wonder why NyQuil is outside of quotes. Did a professor of medicine really make such an unbelievable mistake?
It's more likely the professor either talked about NyQuil in a follow-up question where the direct quote did not flow nicely, or expounded on it in much longer length than the author wanted to quote directly.
As a narcoleptic, I have no trouble falling asleep, the trouble is with staying asleep and getting deep rest during my sleeping periods. I've found that some nutritional strategies work tremendously well.
> #1: Eat More Protein During the Day & Select Carbs at Night
> ... eating a meal of carbohydrates in the evening can help you go to sleep quickly.
This is curious. I've run across this advice before. I have also found, from repeated experiments, that eating starchy foods just before bed makes it harder for me to go to sleep. Maybe I have some weird body chemistry ....
You might want to get sleep tested. Sleep apnea is a common problem that robs people of deep sleep and can be treated, most commonly with a device that applies positive air pressure to breathing passages during sleep. Many variations are available to match different physiologies.
Firstly, the article is open why not simply link it? Second -- people take these medications to help them sleep. Difficulty sleeping is a comorbidiy of dementia. I haven't made it through the paper yet -- but pointing out anything other than association seems awfully premature.
Not necessarily. If they were able to sufficiently test for confounding variables, it'd be a reasonable conclusion. The news article specifically states they were able to control and remove overlap with existing dementia cases. Question is how well it's done, and I don't have time to examine the OP. Post if you notice anything?
Poked around a bit and ran across at least one article [1] that advises caution but also points out that these results are seen in fairly high/frequent doses, are still being studied, and that anyone prescribed or currently taking an anticholinergic medication should check with their doctor before just stopping the drug. The way I see it, not everyone is necessarily at risk and as with many things, the outcome of not taking the medication could be worse than the potentially higher risk of negative outcomes from taking the medication.
Can we have the data to see if their statistics are good and that they applied the right techniques to clean their data? I don't trust any medical study much anymore because next week one will come out refuting this claim.
Ask the author. The paper says they had full access to their data. They might be able to pass an anonymised version of that along. They might even be willing.
The process of scientific discussion (that you "don't trust") is just how science works.
I suspect what you actually dislike is the way these papers are cross-reported. It's one thing to be featured in a relevant journal, it's another to be syndicated as "THE CURE FOR DEMENTIA" by a much higher-level journal (or heavens forbid, a newspaper... or worse).
You can blame the sponsors and drug companies for that. Neither of which really seem to be involved here.
> The process of scientific discussion (that you "don't trust") is just how science works.
The invisibility of the data upon which papers rely is one of the key weaknesses of science as currently practiced, as it makes verification of analysis impossible. I don't think it has to be "how science works", and in fact I hope that science moves away from such opacity to requiring data to be published alongside papers.
Even if you have all that, you still need to trust that the data was collected as described and without any hidden biasing effects – so, again, you're trusting the authority of the author(s)...
It's turtles all the way down, in some ways, but I don't disagree with you – code and data are a critical first step and they enable both the verification of findings and better chances at accurately testing the verifiability of the research. It's much better to go out and get your own data and compare apples to apples with the same analytic process (assuming you agree with the analytic process which you should assess even before collecting data, but I digress...)
Thanks for the link. This is somewhat concerning as I currently take two drugs on that list (promethazine, amitriptyline), though TBH given the improve they provide to daily life I think it is an acceptable, unfortunate risk.
While not a new result, it is very scary none-the-less. Some of those drugs are a daily goto for many people to handle various issues. I hope medical professionals will take this result into account before recommending them for any longterm treatment.
Most of this stuff is available over the counter - so medical professionals don't even need to be consulted. I hope they pull it behind the counter if the results are corroborated. It would make handling allergies a pain though.
IMO, Claritin is only sufficient for minor sinus drip at the start of pollen season, for example. It does nothing for the significant draining during the height of allergy season and colds laugh at its feeble attempts to stop sinus drainage.
Of course, Claritin does nothing to help a stuffy nose. It's the wrong class of medicine. True pseudoephedrine (from behind the counter) is the go to for increasing drainage. The new stuff (OTC with phenylephrine) only works as well as a placebo.
Loratadine is in a completely different drug class than pseudoephedrine, the article is recommending it as an alternative to Benadryl.
Loratadine and Benadryl are antihistamines, pseudoephedrine is a stimulant that has a decongestant affect.
There's Claritin branded combo pills that have Loratadine and a decongestant, but "Claritin" in normal conversation should probably be reserved for the one active ingredient Loratadine pills.
The new stuff (OTC with phenylephrine) only works as well as a placebo.
That's going to depend on the person, at least as a nasal spray, for me at least it has a noticeable effect that I'm certain isn't placebo. Back when I took it, systemic oral pseudoephedrine (Sudafed) was noticeably better (stopped that route due to it exacerbating my anxiety).
Fortunately, there are nasal steroid sprays, and 2 of them are now OTC, and you can get a prescription for the azelastine antihistamine nasal spray (Astelin, Astepro), the latter ought to pose little risk to your brain. A combination of the two, with occasional very short courses of nasal spray phenylephrine (4 hour) or oxymetazoline (12 hour) curbed my rate of getting sinus infections from more than 1 a year to one every few years.
Oral phenylalanine has never done anything for me (24mg; no improvement or side-effects), even for relatively severe sinus infections. On the other hand, oral pseudoephedrine (120mg) is the closest thing to a miracle drug I have ever used - I go from being nauseated (from pain) every time I bend down to feeling somewhat OK (I suffer from near-constant headaches anyway, so difficult to really judge) in about twenty minutes.
Fortunately, it's still easy to get in the UK, and doesn't exacerbate my anxiety.
The 120 mg is the 12 hour sustained release formula, right?
I never tried that, in fact I'm pretty sure I stuck to the 30 mg immediate dosing version, which was useful but not quite a "miracle drug", then again I'm sure our sinuses are quite different. So I haven't really missed it, between the effect on anxiety, and much later living in a notorious area for meth, where my usual pharmacy is in a city where even dispensing of OTC versions requires a doctor's prescription.
If my doctors really wants to clear my sinuses while treating for an infection, they use a Medrol DosePak (serious steroid with a lot up front and then it quickly tapers), something my father is all to familiar with due to his poison ivy allergy and ability to get into the stuff.
> The 120 mg is the 12 hour sustained release formula, right?
It's two of the 60mg "Sudafed Decongestant" (UK Branding) tablets, which I don't believe are sustained release (typical/listed dose is 60mg - I confirmed with my GP that 120mg is fine FOR ME [do NOT take this as general advice] if taken infrequently). I generally only need a single dose during the day for my sinuses to stay clear enough to be manageable (and sinus infections are infrequent anyway), so the large upfront dose works for me and is well under the daily recommended maximum (240mg).
Claritin makes me feel weird, sort of light headed.
Back in the eighties in Seattle I would take a Benadryl every morning, because I was allergic to just about everything (I was poke tested). Eventually I downgraded to chlor-trimaton. So I guess I'm potentially doomed.
You could try looking into factors to actively reduce your risk. Exercise, eating healthy, and drink lots and lots of coffee. E.g. It's all poker and you're down on the pot but it just means you need to learn to play a different better hand. At least it's the approach I found to be beneficial.
It's certainly the only sane approach, I agree. It's like Lyle Lovett said, "You have to try ..."
My mention of doom is because I got the impression that the rise in risk (10%) was associated pretty hard with long term use, which I had, and distant past wasn't mentioned as a mitigation.
since loratadine is a second-generation histamin receptor blocker, probably not if you are looking for sedating effects, because minimizing those was the main reason for developing this class of drug.
I was thinking mostly of the boards that decides what is allowed OTC and what needs a prescription. Regardsless, people should consult their doctor if they have a long term issue, regardless if it can be controlled with OTC medicine or not.
"Another implication of the ability of cholinergic
antagonists to promote dementing diseases is that sufficient choline needs to be provided so that adequate PC
production can continue. This might most effectively
be done by administering the choline as a component
of a nutrient mixture that contains all three of the PC
precursors which limit PC’s rate of synthesis: uridine
as its monophosphate; DHA or EPA; and choline [24].
This mixture has been shown to diminish Aβ formation in experimental animals [32], and could have the
added benefit of partially restoring the deficient brain
synapses."
I'm reminded that health freaks have recommended supplements containing phosphatidylcholine and precursors for many years. It does make sense, in that phosphatidylcholine is a bipolar lipid, and plays important roles in cell membranes.
This is consistent with the Cholinergic hypothesis[1] of Alzheimer's disease. Also, note that the various hypotheses for Alzheimer's are not really "competing", so this doesn't mean that the more recent lines of research are any more or less valid.
Alarming stuff! I've no problem giving up Benydryl, but my partner takes Disiprimine,and it's the only drug she's found that works well for her depression :-(
From the source [1]: "study participants 65 years or older were sampled randomly from Seattle-area GH members. Participants with dementia were excluded. The original cohort of 2581 participants was enrolled from 1994 through 1996. An additional 811 participants were enrolled from 2000 through 2003. In 2004, the study began continuous enrollment to replace those who died or dropped out."
The suggested mechanism is that coal tar derived medicines trigger a self sustaining inflammation reaction which causes generation and accumulation of amyloid plaques.
Most peoples anti-hayfever drugs will be 'second generation' antihistamines, like loratadine and cetirizine, which are not problematic.
More worrying to me is the fact that OTC antiemetic (motion sickness) drugs like Gravol/Dramamine/Vomex/Dramina are made of dimenhydrinate, which is 50% diphenhydramine, which in turn is what the mentioned 'first generation' antihistamines are made of.
Standard Tylenol is paracetamol (aka acetaminophen)... But the article here is talking about Tylenol PM, which is a different formulation. From Drugs.com:
> What is Tylenol PM (acetaminophen and diphenhydramine)? Acetaminophen is a pain reliever and a fever reducer. Diphenhydramine is an antihistamine that reduces the natural chemical histamine in the body.
It's explicitly the anticholinergic diphenhydramine that's being looked at in things like Tylenol PM. Standard paracetamol isn't being questioned, I don't think.
Does anybody know if this also concerns drugs taken with an inhaler? I use an inhaler for allergic asthma and am not sure if the drug is "anticholinergic".
I am not a doctor. Consult your doctor. That said, my non-medical grain-of-salt advice.
Find out the mechanism of action.
1) If the allergy medicine is "anticholinergic" -- same mechanism of action but not the same drug -- then it may or may not have the same side effects.
2) If it is "diphenhydramine" then it likely does have the same side effects (even if different delivery).
3) If it is a different mechanism of action then it likely will not have the same side effect.
If 1 monitor the research, if 3 you probably don't need to worry at all. If 2: talk to your doctor about alternatives. Keep in mind this is just a single study and new evidence may overturn current evidence. But the side significance and magnitude of the effect I would say is cause for concern (again just one study I expect there will be many more).
Presumably one takes it by an inhaler so that it goes directly to the trachea/lungs/etc instead of having to get absorbed through digestion, get distributed in the bloodstream, survive the liver, and finally make it to the needed areas.
What's better, putting off a small, previously unknown risk of a condition you might either not live to develop or may have developed regardless, vs incapacitating and potentially deadly asthma attacks?
Yeah no drug is without side effects and long-term use of anything should be seriously questioned to be sure it's worth it.
Article claims a 10% increase in the risk compared to those who have not taken the medication. Do not misread that as a 10% risk of developing dementia. So if for example there is an 5% chance of developing dementia in your lifetime, the enhanced risk is now 5.5%
Yes, from the WP article (https://en.wikipedia.org/wiki/Ipratropium_bromide), the anticholinergic in Berodual does not diffuse into the blood and also does not cross the blood-brain barrier, so it seems like you're safe.
Interesting, especially the finding that the dementia is correlated with multiple different anticholinergic drugs, but the counter-argument is simple: people taking lots of medications are probably less healthy in general, and therefore more likely to develop dementia.
Since there's no ethical way to do a prospective study, this is more suggestive than anything else. They admit they don't know the mechanism yet, so take with a grain of salt.
> people taking lots of medications are probably less healthy in general, and therefore more likely to develop dementia.
I have already seen several casual confounds in other comments like this and I have to think the scientist went to stringent lengths to eliminate as many confounds and variables given how strong they claim the link is.
> They admit they don't know the mechanism yet, so take with a grain of salt.
Just because they don't know the mechanism doesn't mean it should not be taken seriously. We barely confident of the mechanism that causes Tobacco/Nicotine to give cancer. Some even argue it isn't even Nicotine but rather the bacteria that is around nicotine that produces carcinogens. And there is a good chance like Nicotine products the cause is probably multifaceted (like coupled vehicles etc.).
That being said I haven't read the study in detail.
> I have to think the scientist went to stringent lengths to eliminate as many confounds and variables given how strong they claim the link is.
Having worked in academic science, I can assure you, every scientist tries to make their findings sound strong.
> Just because they don't know the mechanism doesn't mean it should not be taken seriously.
True. There are many things for which we get good evidence before knowing the mechanisms. But here, I'm not sure the evidence is that good, which is why I think a suggested mechanism of action would go a long way.
The fact that they were able to show a dose-dependent response is pretty damning. I think they controlled pretty well for confounding variables, so I'd consider this more than "suggestive".
Not really, a dose-dependent response can also be explained by hidden variables: people taking stronger doses of medications are likely to be sicker than ones taking lighter doses and therefore, more likely to develop dementia. (E.g., who's probably hurt worse? The person on aspirin or the one on morphine?)
That's not true; I suspect it depends on how many other receptors they hit. One reason Lexapro/escitalopram is liked for its laser precision, in the prescribing information it has the following aside, relevant to receptors it doesn't hit:
"Antagonism of muscarinic, histaminergic, and adrenergic receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular side effects of other psychotropic drugs."
It doesn't hit those receptors, so no, hence its ending with "other psychotropic drugs", the latter explicitly excludes Lexapro from being in that class of drugs.
Got around to reading the primary source. I am surprised there isn't more skepticism from this group, but it may have to do with not having time to read the paper. A few reasons to be skeptical of the results (some are stronger than others):
1) First, required reading for anyone interpreting medical studies: http://jama.jamanetwork.com/article.aspx?.articleid=201218 TLDR; is that ~40% of _randomized_ (generally considered highest level of quality) studies and maybe more are proven wrong by subsequent ones resulting from publication bias. Consider that this would not have been published in a high profile journal if it showed no effect, hence pub bias. In other words, we're not seeing the similarly large analyses that show no effect because they're not published.
2) The adjusted analyses have confidence intervals on the odds ratio that overlap with 1.0 except for the highest dose group. There is evidence of a dose response relationship, but there is a problem in how they measure dose response. Cumulative dose biases towards people who have been on medications for a long time. People who are able to take medications (ie are older) for a long time are at greater risk for dementia.
3) It is problematic that they assume any effect on their endpoint is a class effect (ie true of all anticholinergics). The relationship with one medication may be driving this effect entirely. I would like to see, for example, oxybutynin pulled out of the analysis which is never prescribed for allergies and more often for neurological conditions, which could be an unmeasured confounder depending on how they modeled the comorbidities.
4) Controlled analyses are difficult to do well. Most of the time it controls for linear effects, meaning synergistic effects (which are probably involved in development of dementia) are not captured unless explicitly modeled. I do not see that they did this here.
5) I am further suspicious of the way they obtained fill data. As you are noting, many OTC anticholinergics are not "dispensed" in a way typical of prescription anti-cholinergics. If I bought Benadryl at CVS or even if I bought the pre-packaged bottle at the Group Health pharmacy, it's pretty clear to me that neither of these would be reflected in the data. This skews heavily toward prescription anti-cholinergics, which tend to be given for psych/neuro indications which themselves have an association (though likely not a causal one) with dementia. Again, unclear if they modeled all of these.
Overall, I share the sentiment that medical literature needs to be more open. I think it's unfortunate that current state makes it hard to confirm analyses like these with a great degree of certainty.
For those like myself that freak about this kind of stuff, and did not read through carefully, the effect is pretty small and requires taking a lot of benadryl:
"Three years of taking either daily Benadryl, Advil PM, Tylenol PM, or Motrin PM, for example, is associated with about a ten percentage point increase in the probability of experiencing dementia or Alzheimer's compared to no use."
I can't speak to the size of the group, but I would certainly fall within it. For my condition (dermatographic urticaria), the newer drugs (loratadine, desloratadine, cetirizine, fexofenadine) provided very little relief and quickly lost efficacy. Diphenhydramine (and later promethazine, with also has anti-cholinergic effects) provide significantly better relief, are well tolerated (no noticeable drowsiness), and have retained their efficacy over a number of months.
I don't know if this is a common experience or not, but it's not unheard of.
FDA regulation doesn't encourage manufacturers to look at long term effects.
In granting the initial approval. There's various stuff to watch for bad long term effects, which it must be noted also take a long time to show, and are also known to be tied to uniquely vulnerable sub-populations who won't necessarily be well represented in clinical trials.
Heck, for some time I took a drug what almost certainly would have never gotten approval if anyone had realized it killed the livers of a small number of people taking it, when the total number was large enough. The FDA black boxed it and the original company stopped manufacturing it, but many like me who'd passed the danger period and had no signs of liver problems continued taking a generic version for a while.
If I understand your question, the additional testing is done in the only way that makes sense, on the population at large (that's taking the drug, of course). Drug companies and the FDA are pretty sure they understand the risks of the drug before the latter approves it, and I can't see it making sense to require even larger and longer formal double blind etc. trials. The whole process is already so expensive that it's probably at net killing people compared to backing off some.
See GFK_of_xmaspast's link to the FDA page on Vioxx, where the drug company's monitoring effort pulled the plug before anything else.
I'm saying that if the FDA orders a drug company to conduct post-approval studies and the drug company doesn't actually conduct them, then in how many cases has the drug been pulled off the market?
But that's an obvious statement that has little to do with "big pharma". We don't have any drugs that are completely free of side effects. Every time you swallow a pill you decide that the benefits outweigh the side effects.
The article states that Loratadine is recommended as an alternative for the relief of allergies. The article didn't explicitly mention Cetirizine but I have done some research and came across another article from 2012 which does include Cetirizine in the same category as Loratadine:
http://www.pharmacytimes.com/publications/issue/2012/april20...
I believe I am safe to continue using Cetirizine and thought some of you may have the same question. I am not an expert on these issues so if I'm mis-understood any of this please let me know.