There's a compelling state interest in preventing unintentional drug overdoses. There's less of a compelling state interest in preventing people from losing tens of dollars buying (at best) marginally useful cold medicine.
So why is the first ⅔ of this article so focused on the weaker case for regulation? It makes me doubt the author's commitment to liberal value of individual freedom! Instead, I fear he just dislikes drug makers and is shoehorning his ideas into an article for a liberal magazine.
The flippant "A pickier FDA doesn’t have to be a slower FDA. We can have abundance for clinical trials..." is really the kicker. I've seen clinical trials abundance ideas that try *not to relax* the current rules (just make them more objectively applied), but I've never seen a serious argument that claims we can make the already-famously-cautious FDA both "pickier" and faster/cheaper.
This was great. A confounding variable is also the extent to which a brand, over the course of a person’s lifetime, can denote a widely differing array of active ingredients. Consumers, I think rightly, conceptualize e.g. “Sudafed” and “NyQuil” as discrete distinct things, and ought not to be expected to fine-parse the ratios that go into them over different points in time. I know I don’t!
There's got to be a keyhole solution here that removes the incentive to soft-defraud the normies while allowing biohackers, desperate sufferers (not necessarily terminal), etc a much broader Right To Try. Perhaps some combination of tougher disclosure requirements (if you haven't passed a strict effectiveness test you have to say so in big letters on the box) and an "accredited patient" status one could attain by demonstrating that one is better educated about medical tradeoffs than your average person and therefore should be allowed to take more risks, similar to how "accredited investors" can invest in weirder and riskier things than the general population.
Great article—it’s wild how much people will pay for guaifenisin and phenylephrine when it is pretty clear they are ineffective.
Clinically I think disease burden is much higher with OTC sleeping medicine like Benadryl, ZZZquil, etc which are usually first gen antihistamines. These cause confusion, somnolence, and even delirium in the elderly. Many of my patients take them regularly.
And don’t get me started on caffeine pills, kratom, or MJ. Even if we don’t require prescriptions I think clear dose limits and warning labels could be helpful.
In addition to the fact that many of these brands used to contain pseudoephedrine, others contained drugs such phenylpropanolamine and dexbrompheniramine. When the FDA made phenylpropanolamine illegal, I suspect many people just kept buying the brand name drugs that used to work. Given that so many Americans still don't understand generics, I'm sure they don't read ingredients on these combo drugs, either.
The phenylephrine saga is indeed ridiculous, but this article omits an important detail: it is actually an effective *topical* decongestant, i.e. it works just fine in a nasal spray. Using it orally was never really indicated by any science-based reasoning.
I think the overall vibe of this piece (combo drugs are bad, OTC medications are often a scam, etc.) to be basically correct, but your read on dextromethorphan is just egregiously overconfident to the point of being basically false. For one, you're committing a cardinal sin of commenting on pharmaceutical studies: you are linking a meta-analysis that supports your conclusion without seeing if there are contrary meta-analyses (there are a few). Moreover, even in that meta-analysis itself, DXM is bucketed with 'antitussives' and it is said that 'antitussives' generally do not show evidence above placebo. However, of the three studies for DXM in adults that are actually reviewed, two out of the three find significant effect!
One other thing to keep in mind is that cough is remarkably placebo-sensitive. This makes it pretty challenging to tease out a statistically significant effect even if there is a real treatment effect occurring, because the placebo effect is comparably quite large. Now, given that DXM does have risk of adverse side effects, this is actually an independent reason to prefer *not* taking it, since if you can find a placebo you believe in you will probably notice some improvement. Your reference to honey is an example of this -- it's easy to read this as saying 'it's no more effective than some made up home remedy' while, in fact, honey is quite potent as cough relief compared to doing nothing.
That all said there is pretty strong evidence that 1) DXM should probably not be given to children, since the doses are sub-therapeutic and there has never been strong demonstration of a regimen that works in children and 2) the amounts of DXM in dayquil and similar drugs is *really* small compared to what has been shown to be effective in trials, which is one of the flaws of the combo drug concept as a whole (you can't control your DXM dosage independently of your acetaminophen dosage).
In short, if you are the sort to prefer natural remedies, you should be content with tea and honey. If you find that you are more reassured by something with real medicinal effect and a plausible mechanism of action, DXM is at least as good as the tea and honey and probably better. There is nothing wrong with buying a bottle of DXM syrup that is *not* packaged with acetaminophen (this can be hard to find in your average drug store unfortunately, as DXM can be abused as a recreational drug and has been combined with acetaminophen to destroy the livers of unsuspecting adventurous college students, which is an abominable practice and worth discussing another time)
(Methamphetamine should be legal – sell it in '(otherwise) banned goods' stores – and then let us buy pseudoephedrine NOT under surveillance.)
It's particularly pernicious to want to take a placebo of all things "off the market" – if it's really a placebo, then its users experience it working AND it's not actually harming them.
Sudafed is welcome to put phenylephrine on the homeopathy shelf with the other placebos. But the FDA should not be endorsing a manufacturer's false claims about what a drug can do
It seems like we agree that some 'drugs' are placebos and, e.g. I think the balance of evidence is that vitamin supplementation is unnecessary for almost everyone too – ALL the shelves are full of placebos.
The FDA should absolutely not endorse anyone's false claims, or likely/probably/maybe false claims, but that seems like it should (possibly) be distinct from 'taking something off the market'.
Dextromethorphan isn’t just a neutral “placebo” - you can trip on it if you want. (“Robo-tripping”, I think the kids used to call it, because it was in robitussin.)
Most of the other ingredients in robitussin would count as neutral placebos by this standard! No one is tripping on grape flavoring or purple food coloring, just DXM!
Tho I guess I can't help but quibble that, of course, 'placebo' is a fuzzy category and I'd guess it IS effectively a placebo for most of its users, given that robo-tripping requires DXM be "taken far above its standard medical dosage". Someone could push the classic sugar pill past 'placebo nature'!
When I looked at the dextromethorphan section of the Cochrain review referenced above, it did not show that most studies (in adults) showed that it was ineffective, actually they report positive results by multiple metrics in multiple studies. Am I missing something?
"In fact, this is explicitly how the FDA used to operate before Congress changed the standard in 1962."
The way we access information has changed a bit since 1962. Given those changes, don't you think that the way the FDA functioned in 1962 would actually be more appropriate in modern times than it was back then?
If you're so smart and such a careful reader, why aren't you carefully reading the label and then putting it back on the shelf and not buying Dayquil, since it's a scam product whose active ingredient can be received through other, cheaper means?
I don't know that seems like the most normal thing in the world to do when you're taking potentially lethal chemicals in your body. If i'm not doing it it's because i've been using the same formulation forever like say Dayquil that i could tell you exactly what's the same or different in generics.
Maybe this is one of those things I do that's actually totally weird it wouldn't shock me.
There are effective cough suppressants: opiates. Typically this is only used in palliative situations, for obvious reasons. Codeine works decently well too but has similar downsides.
If I only had the political capital to go after one category of OTCs, I’d probably go after the first generation antihistamines. My totally non-evidence based and very-much-anecdote-based reasoning for this is that I’ve only seen unintentional Tylenol overdose from combo meds once, but I see falls/complications from Benadryl ***all the time*** from people who take it for insomnia. Some limitations (ie not being able to buy Costco sized containers of Benadryl) would help.
Could be totally wrong though, and unintentional Tylenol toxicity could be way more prevalent than I think. Curious if the folks who work in the ED have an opinion on this.
It's good to know that my "this doesn't do shit" evaluation of phenylephrine is supported by science.
I will say that I find Excedrin and Nyquil convenient. It's true that I'd just rather take one pill or syrup shot instead of sorting out 3. The acetaminophen overdose issue is compelling, however, and I would switch without issue if I had to.
Possibly we should have some kind of medical literacy as part of school science education. As a country, we seem to leave it mostly up to parents and family medicine to explain how to read drug labels and warn about overdoses and interactions, and it might be better to just address this stuff in 7th grade biology. The kids wouldn't be able to complain it wasn't relevant to their lives.
There's a compelling state interest in preventing unintentional drug overdoses. There's less of a compelling state interest in preventing people from losing tens of dollars buying (at best) marginally useful cold medicine.
So why is the first ⅔ of this article so focused on the weaker case for regulation? It makes me doubt the author's commitment to liberal value of individual freedom! Instead, I fear he just dislikes drug makers and is shoehorning his ideas into an article for a liberal magazine.
The flippant "A pickier FDA doesn’t have to be a slower FDA. We can have abundance for clinical trials..." is really the kicker. I've seen clinical trials abundance ideas that try *not to relax* the current rules (just make them more objectively applied), but I've never seen a serious argument that claims we can make the already-famously-cautious FDA both "pickier" and faster/cheaper.
Honestly, dextromethorphan is one of my favorite placebos.
I always feel a little better.
This was great. A confounding variable is also the extent to which a brand, over the course of a person’s lifetime, can denote a widely differing array of active ingredients. Consumers, I think rightly, conceptualize e.g. “Sudafed” and “NyQuil” as discrete distinct things, and ought not to be expected to fine-parse the ratios that go into them over different points in time. I know I don’t!
There's got to be a keyhole solution here that removes the incentive to soft-defraud the normies while allowing biohackers, desperate sufferers (not necessarily terminal), etc a much broader Right To Try. Perhaps some combination of tougher disclosure requirements (if you haven't passed a strict effectiveness test you have to say so in big letters on the box) and an "accredited patient" status one could attain by demonstrating that one is better educated about medical tradeoffs than your average person and therefore should be allowed to take more risks, similar to how "accredited investors" can invest in weirder and riskier things than the general population.
Great article—it’s wild how much people will pay for guaifenisin and phenylephrine when it is pretty clear they are ineffective.
Clinically I think disease burden is much higher with OTC sleeping medicine like Benadryl, ZZZquil, etc which are usually first gen antihistamines. These cause confusion, somnolence, and even delirium in the elderly. Many of my patients take them regularly.
And don’t get me started on caffeine pills, kratom, or MJ. Even if we don’t require prescriptions I think clear dose limits and warning labels could be helpful.
In addition to the fact that many of these brands used to contain pseudoephedrine, others contained drugs such phenylpropanolamine and dexbrompheniramine. When the FDA made phenylpropanolamine illegal, I suspect many people just kept buying the brand name drugs that used to work. Given that so many Americans still don't understand generics, I'm sure they don't read ingredients on these combo drugs, either.
The phenylephrine saga is indeed ridiculous, but this article omits an important detail: it is actually an effective *topical* decongestant, i.e. it works just fine in a nasal spray. Using it orally was never really indicated by any science-based reasoning.
I think the overall vibe of this piece (combo drugs are bad, OTC medications are often a scam, etc.) to be basically correct, but your read on dextromethorphan is just egregiously overconfident to the point of being basically false. For one, you're committing a cardinal sin of commenting on pharmaceutical studies: you are linking a meta-analysis that supports your conclusion without seeing if there are contrary meta-analyses (there are a few). Moreover, even in that meta-analysis itself, DXM is bucketed with 'antitussives' and it is said that 'antitussives' generally do not show evidence above placebo. However, of the three studies for DXM in adults that are actually reviewed, two out of the three find significant effect!
One other thing to keep in mind is that cough is remarkably placebo-sensitive. This makes it pretty challenging to tease out a statistically significant effect even if there is a real treatment effect occurring, because the placebo effect is comparably quite large. Now, given that DXM does have risk of adverse side effects, this is actually an independent reason to prefer *not* taking it, since if you can find a placebo you believe in you will probably notice some improvement. Your reference to honey is an example of this -- it's easy to read this as saying 'it's no more effective than some made up home remedy' while, in fact, honey is quite potent as cough relief compared to doing nothing.
That all said there is pretty strong evidence that 1) DXM should probably not be given to children, since the doses are sub-therapeutic and there has never been strong demonstration of a regimen that works in children and 2) the amounts of DXM in dayquil and similar drugs is *really* small compared to what has been shown to be effective in trials, which is one of the flaws of the combo drug concept as a whole (you can't control your DXM dosage independently of your acetaminophen dosage).
In short, if you are the sort to prefer natural remedies, you should be content with tea and honey. If you find that you are more reassured by something with real medicinal effect and a plausible mechanism of action, DXM is at least as good as the tea and honey and probably better. There is nothing wrong with buying a bottle of DXM syrup that is *not* packaged with acetaminophen (this can be hard to find in your average drug store unfortunately, as DXM can be abused as a recreational drug and has been combined with acetaminophen to destroy the livers of unsuspecting adventurous college students, which is an abominable practice and worth discussing another time)
Placebos should be legal!
(Methamphetamine should be legal – sell it in '(otherwise) banned goods' stores – and then let us buy pseudoephedrine NOT under surveillance.)
It's particularly pernicious to want to take a placebo of all things "off the market" – if it's really a placebo, then its users experience it working AND it's not actually harming them.
Sudafed is welcome to put phenylephrine on the homeopathy shelf with the other placebos. But the FDA should not be endorsing a manufacturer's false claims about what a drug can do
It seems like we agree that some 'drugs' are placebos and, e.g. I think the balance of evidence is that vitamin supplementation is unnecessary for almost everyone too – ALL the shelves are full of placebos.
The FDA should absolutely not endorse anyone's false claims, or likely/probably/maybe false claims, but that seems like it should (possibly) be distinct from 'taking something off the market'.
Dextromethorphan isn’t just a neutral “placebo” - you can trip on it if you want. (“Robo-tripping”, I think the kids used to call it, because it was in robitussin.)
Sure – but by that standard, nothing is a neutral placebo. Someone could kill themselves taking too much of a homeopathic solution in water.
Most of the other ingredients in robitussin would count as neutral placebos by this standard! No one is tripping on grape flavoring or purple food coloring, just DXM!
Say no to 'the war on tripping' too! This is almost entirely just another avenue by which we've lost nice things.
I agree with that! I’m just saying that something that enables you to trip isn’t just a placebo.
I agree with that!
Tho I guess I can't help but quibble that, of course, 'placebo' is a fuzzy category and I'd guess it IS effectively a placebo for most of its users, given that robo-tripping requires DXM be "taken far above its standard medical dosage". Someone could push the classic sugar pill past 'placebo nature'!
When I looked at the dextromethorphan section of the Cochrain review referenced above, it did not show that most studies (in adults) showed that it was ineffective, actually they report positive results by multiple metrics in multiple studies. Am I missing something?
"In fact, this is explicitly how the FDA used to operate before Congress changed the standard in 1962."
The way we access information has changed a bit since 1962. Given those changes, don't you think that the way the FDA functioned in 1962 would actually be more appropriate in modern times than it was back then?
Guaifensin works
Expecting people to read the labels of drugs for tbe active ingredient is too much work really?
I don’t want to say anything mean but
It feels very nanny state. When I take my DayQuil I carefully check everything else for acetaminophen in particular. It’s not that big of an ask.
If you're so smart and such a careful reader, why aren't you carefully reading the label and then putting it back on the shelf and not buying Dayquil, since it's a scam product whose active ingredient can be received through other, cheaper means?
Because liquid DayQuil is magic when I have to work sick and you can just take my money and taste disgusting.
What percentage of people who have bought OTC medication in the US in the last year do you think do this? I would guess ~5%.
I don't know that seems like the most normal thing in the world to do when you're taking potentially lethal chemicals in your body. If i'm not doing it it's because i've been using the same formulation forever like say Dayquil that i could tell you exactly what's the same or different in generics.
Maybe this is one of those things I do that's actually totally weird it wouldn't shock me.
What about stuff like zinc lozenges with some evidence?
https://pubmed.ncbi.nlm.nih.gov/8678384/
There are effective cough suppressants: opiates. Typically this is only used in palliative situations, for obvious reasons. Codeine works decently well too but has similar downsides.
If I only had the political capital to go after one category of OTCs, I’d probably go after the first generation antihistamines. My totally non-evidence based and very-much-anecdote-based reasoning for this is that I’ve only seen unintentional Tylenol overdose from combo meds once, but I see falls/complications from Benadryl ***all the time*** from people who take it for insomnia. Some limitations (ie not being able to buy Costco sized containers of Benadryl) would help.
Could be totally wrong though, and unintentional Tylenol toxicity could be way more prevalent than I think. Curious if the folks who work in the ED have an opinion on this.
Great article. Thanks!
It's good to know that my "this doesn't do shit" evaluation of phenylephrine is supported by science.
I will say that I find Excedrin and Nyquil convenient. It's true that I'd just rather take one pill or syrup shot instead of sorting out 3. The acetaminophen overdose issue is compelling, however, and I would switch without issue if I had to.
Possibly we should have some kind of medical literacy as part of school science education. As a country, we seem to leave it mostly up to parents and family medicine to explain how to read drug labels and warn about overdoses and interactions, and it might be better to just address this stuff in 7th grade biology. The kids wouldn't be able to complain it wasn't relevant to their lives.