Hacker News Reader

Comment by Aurornis | Hacker News Reader

This article uses the trick where you pick studies that support your argument and ignore all of the studies that disagree with it.

There are other studies where Dextromethorphan improves both objective and subjective measures of coughing: https://pubmed.ncbi.nlm.nih.gov/37232330/

They also picked a study that shows honey outperforming Dextromethorphan but ignored all the studies that show honey performing similarly or slightly worse than Dextromethorphan, or studies where honey showed no measurable effect.

There are so many studies and papers published now that you can find both positive and negative results for just about anything. When someone starts pulling up singular random links to papers you should be suspicious. Be even more suspicious when someone is calling for bans or regulations based on those individually selected papers

View on HN

I work for a large agricultural company, in my part of it we sell fertilizer, chemical, and agronomic services. As part of this, we end up putting out a lot of trials so we can actually say something true instead of “buy our stuff it’s great I promise ;)”

One of my favorite slides is when we compiled dozens of trials on something that’s basically a nitrogen fertilizer, which as much of a guaranteed positive effect as you can get in agriculture. When compared in a graph most of the trials show an overwhelming effect on increasing yield over an untreated check, however there’s always a portion of the trials where the yield decreases compared to the (untreated) check.

Real life is extremely noisy for a multitude of circumstantial reasons that are either not practical or possible to control for, so a single trial is generally worth fuckall. It takes a lot of testing to see a consistent trend across them.

DXM may or may not suppress coughing relative to placebo - the study cited here appears to be have been written entirely by authors from drug companies, so perhaps there is some bias. Here's a meta analysis that favors honey over DXM https://pubmed.ncbi.nlm.nih.gov/32817011/, the original study that kicked off this idea that also favors honey https://pubmed.ncbi.nlm.nih.gov/18056558/, and a different meta analysis https://pmc.ncbi.nlm.nih.gov/articles/PMC6513626/ which found little or no difference between honey and DXM. Whether its effective or not, to me there doesn't seem to be compelling evidence that it is more effective than honey.

It's funny that TFA seems to use the comparison to honey as disparagement, rather than interpret the same information as an endorsement of the helpfulness of honey.

I think the point is honey is known as a home remedy, may already be in your house and is available at a much lower price (farmer’s markets and woo merchants possibly excepted).

Honey is also well established in medicine, especially in wound and infection management. I'm not sure of how much clinical evidence supports cough suppression, but it not huge leap to suspect that it could be a second order effect of its antibacterial properties, like in bacterial bronchitis.

It's worth nothing that all of the studies you linked were performed only on children. It is entirely plausible that DXM is effective in adults but not children because of the difference in dosage or measurement (studies on children often rely on parental surveys).

And, all of this, to avoid selling a little bit of the narcotic codeine. Which was technically permitted to be sold "behind the counter" without prescription, but was made Schedule II as part of cough syrup in the US not long ago. (It used to be Schedule III or IV when combined with homoatropine or promethazine).

100%

I wonder if the cost benefit analysis would show that this is still the best policy - I.e. are more people dying because of overdose of acetaminophen than would have from “behind the counter” + controlled acquisition of codeine products.

I would also imagine that the compliance / nationwide tracking is now much easier than when the legislation was initially conceived.

I think it was a mostly innocent bystander, because they decided to put codeine-combination painkillers (Vicodin, etc.) in schedule 2 but wrote it as just opiate combination medicines.

Codeine is still sold in many countries otc, as part of weak pain killer combination or as part of cough medicine.

I miss codeine cough syrup. It's the only thing that's ever been effective for me, despite my being fully immune to the "fun" aspects of opiates. They do remove pain, coughing, etc, but do not add any sensations or impair normal ones in my case. I've tried most of the gamut in one medical setting or another.

There should be a class of drug where the pharmacist gets to decide, based on some registry, whether you get to have something.

It's still available, I just don't know if it's still available without prescription. It's also gotten more expensive and not as many pharmacies stock it. Really, I find our drug policies so frustrating.

They should take all the ineffective phenylephrine products off the market and educate the consumer about asking for pseudoephedrine versions. But I think the ship has sailed and meth is being made with industrial chemicals now, so the restriction isn't as useful as it was.

I think it's not a bad idea to have a registry to prevent over-dispensing of opiate cough syrup. It's really an important drug. There are a lot of conditions that cause chronic, lifelong, unproductive coughing. Doctors end up prescribing things that are either more habit-forming or more dangerous.

Just buy poppy seeds in bulk and make a tea. They wash 'em, but not enough to get all of the opium off the outside. Okay but really maybe don't do this unless you're gonna be careful because I actually have known a guy who ended up with problematic morphine habituation this way.

That said, dextromethorphan works just fine on its own (if you take enough -- 2 tsp is nonsense). Why they feel the need to mix in a bunch of other actives is beyond me.

An interesting new drug is Auvelity, where Dextromethorphan is proposed to help stimulate neurotropic growth factor to help the brain repair itself, and similar related drugs like dextromethorphan and ketamine and other NMDA receptor antagonists are innovative drugs to help prevent Alzheimer's.

> An interesting new drug is Auvelity, where Dextromethorphan is proposed to help stimulate neurotropic growth factor to help the brain repair itself,

Auvelity is interesting, but the exact mechanism of action is not very clear.

Auvelity is a combination of two drugs: Dextromethorphan and Bupropion. Bupropion, aka Wellbutrin, is an antidepressant by itself. In Auvelity it helps alter how Dextromethorphan is processed by the body, but we can't rule out that it contributes to the antidpressant effect. I mean it's literally an antidepressant.

Dextromethorphan has a lot of interactions and gets a lot of comparisons to ketamine because it has NMDA affinity, but if you look at the table of receptors it interacts with the serotonin receptor is one of the strongest interactions. It is a potent serotonin reuptake inhibitor, which is also known to have antidepressant effects. It also has some sigma receptor interactions which might be doing something significant.

The NMDA interactions get all of the attention because if you put "ketamine" in the headline you get a lot more attention, but NMDA may be much lower on the list or even negligible for this combo.

This is straying a bit from the original post, but agreed, NMDA antagonists and related compounds effecting glutaminergic tone are showing promising directions.

N=1, I've had very positive experiences with DIY Auvelity, using 150mg Buproprion XR that I'm RX'ed with 60mg OTC DXM-only tablets.

> … similar related drugs like dextromethorphan and ketamine and other NMDA receptor antagonists are innovative drugs to help prevent Alzheimer's.

Should read “NMDA receptor antagonists _may_ give rise to treatments that _may help prevent or ameliorate the symptoms_ of Alzheimer’s.

Nobody even knows how Alzheimer’s works at all — like most diseases it’s a description of some detectable symptoms, some of which could even turn out to be the body defending itself.

Thus compounds that may have a mechanism of action that affects some concomitant, visible symptoms might potentially be useful.

The use of definitive sentences about unknown results is how we end up with wellness and some “biohacking” nonsense.

They're referring to Memantine, an NMDA antagonist that has been approved for treating symptoms of Alzheimer's for over 20 years.

Haven't heard of Alzheimer's. What kind of use is necessary ? I would assume something like an ultra low dose but daily thing ?

Memantine https://medlineplus.gov/druginfo/meds/a604006.html

Wow -- that's a combination I only remember people being highly cautioned against at least for recreational use.

> This article uses the trick where you pick studies that support your argument and ignore all of the studies that disagree with it.

It's even worse than that, they appear not to have actually read the analysis they cited because two of the three studies on DXM found it was effective in adults. The same efficacy was not found in children but there are other very plausible explanations for this (difference in dosage and measurement techniques).

I was wondering about that. I've taken a number of different cold medications over the years, one active ingredient at a time, to check their effectiveness while sick. Phenylephrine, as widely reported, had zero effect. But Dextromethorphan seemed to work for my kids - give it to them, stopped coughing. Started coughing again 6 hours later, etc. n=1 and it's a 4 year old, but in one of those cases my results clearly matched the studies, and in the other it didn't, at least as reported by this article.

In my subjective experience, Dextromethorphan (DXM, as the robo-trippers call it) does almost nothing for me, in the 1-5% range

The only cold and cough medicine that really truly works is the over-the-counter stuff, pseudoephedrine, works amazing for me. I usually pick up a box of the stuff when school starts in the fall and I go through half a box of it by the following summer.

Pseudoephedrine is a decongestant to relieve the nasal/sinus congestion.

If it helps with your coughing, it’s because it’s stopping the postnasal drip, not suppressing the cough as DXM would by shutting down the cough reflex.

Two different, but very similar use cases. DXM is a god-send in the appropriate time.

Are you sure you posted the right paper? That paper appears to present a clinically insignificant outcome for DXM in children.

I think it's perfectly reasonable to contest the research summary this article is providing. All science-based articles on interesting topics are going to be like that. But you're writing your comment as if they took a flyer on DXM, and the research consensus is in fact that DXM is not effective. It's not as bad as phenylephrine (it has detectable, if immaterial, impact in adults), but it's pretty bad.

The point of the article, of course, isn't that Dayquil should be illegal because it's dangerous; it's that it doesn't work. Having spent an unreasonable amount of time in HN pseudoephedrine threads, I think the broad consensus of this site is that phenylephrine should be taken off the shelves.

Phenylephrine was the replacement that doesn't really work but is non (or less) stimulating right ?

From what I remember it was actually quite effective topically but not through pill form. Could be wrong.

Also makes me wonder if there's an alternative function to DXM for people with colds (maybe it makes them feel better in other ways). Or it's just good marketing and associated with NyQuil having other drugs and people assuming DayQuil works

It's not that it's less stimulating, it's that pseudoephedrine basically is methamphetamine (the chemistry to reduce it to meth is truck-stop straightforward). But oral phenylephrine doesn't work at all.

The case against DXM is nowhere nearly as good as the case against phenylephrine; phenylephrine is a scam, and DXM is a drug everyone thought was the gold standard cough suppressant, but then serious studies knocked down its effectiveness.

I don't know if OP changed their link but the one currently in their post (https://pubmed.ncbi.nlm.nih.gov/37232330/) did find DXM to be effective:

"Using objective and subject assessment tools validated in pediatric populations, this study provided evidence of the antitussive efficacy of DXM in children, aged 6–11 years, at the current OTC monograph dose and labeled indication. Compared with placebo, DXM treatment reduced cough rates 21.0% over 24 h (primary endpoint) and 25.5% during daytime/awake hours. In addition, children treated with DXM reported greater reductions in cough severity and frequency in the mornings and afternoons over 3 days than children treated with placebo. These treatment effects were statistically significant despite the study not reaching its planned sample size and are medically relevant."

Also as I mentioned in another comment, the author of original article misrepresents the findings of their own citation. DXM was found to be effective in adults, just not children.

> ignored all the studies that show honey performing similarly or slightly worse than Dextromethorphan, or studies where honey showed no measurable effect.

To be fair, you're doing pretty much the same by claiming these studies exist without proof.

Isn't it a bad sign that there are such varied results? Perhaps that's only a bad sign for the state of science, but I suspect it's also a bad sign for the effectiveness of the drug.

> There are so many studies and papers published now that you can find both positive and negative results for just about anything.

Doesn’t that suggest that the effect overall is neutral?

You can find positive and negative results for everything.

If that implies the effect is neutral, then by extension that means nothing works at all.

No, you can't just "average" different studies and I'm not sure what "neutral" means in the context of some studies showing a benefit and others not showing a benefit.

Only if you assume that all studies are valid and accurate. And even then you are drawing the wrong conclusion -- if everything is "neutral" then that means that all the positive studies are wrong and all the negative studies are correct. (You seem to have erroneously assumed that a negative study means that something is bad for you.)

Also, the very claim that there are positive and negative studies for everything is handwavy nonsense. There might 100 studies, all of which agree except for one outlier ... what does that "suggest" to you?

Reply on news.ycombinator.com