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Medicine

How Two Pharmacists Figured Out That Decongestants Don't Work (scientificamerican.com) 143

In 2005, the reclassification of pseudoephedrine to behind-the-counter status led to widespread use of oral phenylephrine in OTC decongestants, despite evidence of its ineffectiveness. Randy Hatton, a clinical professor in the College of Pharmacy at the University of Florida, and his colleague worked to bring this issue to the FDA's attention, revealing loopholes in the regulatory process for older OTC drugs. Hatton writes in an opinion piece for Scientific American: Before the FDA required that drugs had to be proven effective, it determined whether OTC drugs were effective through expert panels that reviewed existing data. These OTC monographs establish what older OTC ingredients can be marketed without FDA approval. The oral decongestant monograph panel reviewed a few published studies and multiple unpublished studies for phenylephrine. Of the unpublished studies, only four studies showed oral phenylephrine was effective, while seven showed it was no better than placebo. We requested copies of all evidence used by the nasal decongestant review panel via a Freedom of Information Act request and performed a systematic review and meta-analysis ourselves. [...]

The FDA has multiple regulatory processes for different types of medicinal compounds. People are perhaps most familiar with the New Drug Application process, which leads to clinical trials for prescription drug approvals. However, many OTC or nonprescription drugs are regulated differently. In fact, a law passed in 1951, the Durham-Humphrey Amendment to the 1938 Food, Drug, and Cosmetic Act, created the categories of prescription and nonprescription drugs. In 1962, the act was amended again so that drugs had to be shown to be effective, hence the requirement for well-done clinical trials. But what about the drugs that were approved before 1962? This is the loophole that some OTC drugs fall through. For prescription drugs, FDA tried to address pre-1962 approvals through a review of over 3,000 prescription drugs. Most of those drugs have now been reviewed and addressed, but there are still unapproved prescription drugs on the market today, such as an extended-release form of oral nitroglycerin. For nonprescription drugs, FDA established the OTC monograph process 10 years after the 1962 amendment to the Food, Drug, and Cosmetic Act, which required products not proven effective to be reconsidered. FDA formed advisory panels grouping hundreds of ingredients into 26 categories based on the products' uses. After gathering all available information, both published and unpublished, from manufacturers, the advisory panels issued final reports to FDA about whether these ingredients were GRASE (generally recognized as safe and effective), not GRASE, or inconclusive. GRASE ingredients can be used in nonprescription drugs without FDA approval if the use matches the monograph.
"The oral phenylephrine example shows that FDA needs more funding to look at these old drugs," concludes Hatton. "We need public funds to support independent researchers who want to examine these products objectively. The government should be able to spend millions to save consumers billions on ineffective products. Companies that market these products have no incentive to prove they don't work. Nonprescription drugs must be effective -- not just safe."
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How Two Pharmacists Figured Out That Decongestants Don't Work

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  • by bradley13 ( 1118935 ) on Friday December 22, 2023 @05:48AM (#64098395) Homepage

    ...and you will destroy the market for quackery like homeopathy, acupuncture, and other placebos.

    Would that be a good thing or a bad thing? Serious question. One the one hand, people with actual illnesses should get actual, effective treatment. They shouldn't be deceived into thinking that sugar pills will cure their cancer.

    On the other hand, placebos have a genuine role to play. They are great for hypochondriacs, and prevent them from taking care from people who actually need it. Placebos also (sometimes) have a role for actual illnesses. However, for placebos to work, the patient has to believe in them.

    As a last note: I know a couple of "natural healer" types. They are incredibly nice people, and my bet is that they are functioning more as therapists than anything else. Whatever they claim to do, the real benefit to their patients probably comes from being taken seriously by a nice person who listens to them.

    • by Opportunist ( 166417 ) on Friday December 22, 2023 @06:30AM (#64098437)

      That's what makes alternative medicine so popular: People feel like they're being taken seriously. The quack sits down with them, listens to their ailments, asks questions that they can answer, makes suggestions rather than prescriptions and the patient has the feeling that they are in charge.

      This is actually a pretty powerful thing. There have been studies about how being involved in the "production" of the medication affects its efficacy. Headache medication where the patient had to first dissolve the powder in water, wait for a moment for it to dissolve and then drink the water was more effective than the same medication in the form of a pill that just had to be swallowed. Splitting up the medication into two bags that first had to be mixed increased the chance of resolving the headache even further, even though all the people did was to mix two powders that originally came in a single envelope.

      Even the color of the medication has an impact on how effective it is. Heart medication pills work best with a red cover. Tranquilizer need to be blue. White is always a good color, especially for medication that is supposed to kill germs. And under no circumstances may a pill be black, so even activated charcoal gets a coating so it ain't.

    • The second my doc prescribed acupuncture, I knew he wasn't serious and I got a new one.

      • by Calydor ( 739835 )

        Are you sure you didn't just misunderstand him when he said he needed a lot of blood samples?

        • No, but once a hospital took > 20 blood samples. Like, seriously, and they claimed they could not use the IV and needed to stick me again! Another nurse was so totally distracted and twisting/moving around that the needle came right out and spewed blood all over me. I passed out and the doc said seeing it did something to my blood pressure and I could have died.

          It's a miracle I am not deathly afraid of needles by now!

    • by mjwx ( 966435 )

      ...and you will destroy the market for quackery like homeopathy, acupuncture, and other placebos.

      Sadly no, people who evaluate evidence and effectiveness are already avoiding quackery like homeopathy, acupuncture, vitamin supplements, et al. People who buy this stuff are taken in by the nonsense and will ignore evidence to the contrary.

      Would that be a good thing or a bad thing? Serious question. One the one hand, people with actual illnesses should get actual, effective treatment. They shouldn't be deceived into thinking that sugar pills will cure their cancer.

      On the other hand, placebos have a genuine role to play. They are great for hypochondriacs, and prevent them from taking care from people who actually need it. Placebos also (sometimes) have a role for actual illnesses. However, for placebos to work, the patient has to believe in them.

      As a last note: I know a couple of "natural healer" types. They are incredibly nice people, and my bet is that they are functioning more as therapists than anything else. Whatever they claim to do, the real benefit to their patients probably comes from being taken seriously by a nice person who listens to them.

      Destroying the market for quackery would, beyond any shadow of a doubt, be a good thing. However to do this, you'd need to reduce demand below the critical mass that can support such a market. If a demand exists, someone will fill it. This is why when you illegalise vice

      • by piojo ( 995934 )

        I don't think you can destroy the market for quackery as long as there's something the medical establishment can't cure.

        Plus not all quackery is actually quackery. Yoga and meditation used to be fringe practices in the west--in particular yoga was pretty woo woo. Not only has meditation been vindicated, but it has been adopted into more formal practices like CBT.

        And don't get me started on supplements: they are an unregulated mess, but the effective ones get turned into prescribed medicines in 20 years, and

    • by piojo ( 995934 )

      ...On the other hand, placebos have a genuine role to play. They are great for hypochondriacs, and prevent them from taking care from people who actually need it. Placebos also (sometimes) have a role for actual illnesses. However, for placebos to work, the patient has to believe in them.

      Surprisingly, this turns out not to be true. Here's an interesting study I heard about where people got relief from IBS even when they were told they were taking a placebo:

      https://www.ncbi.nlm.nih.gov/p... [nih.gov]

      At least one person got so much relief from the placebo that she had to keep taking it after the study (knowing it is a placebo) :D

    • I had to chuckle (to myself) one day when I was in one of these natural grocery stores (to buy a specific brand and flavor of ice cream) and someone was trying to return some CBD product complaining that it didn't work. The manager said that the store doesn't take returns on products that don't work. Ah, ha, that's the secret to their business model: Barnum was right.

    • Would that be a good thing or a bad thing? Serious question.

      WTF is wrong with you? Serious question.

      It's BAD, *obviously*. There is no way selling fake medicine to sick people instead of real medicine is a net positive for society.

      This isn't one of those "well both sides have good points..." kind of thing. Selling snake oil is glaringly, obviously, wrong and immoral.

    • Destroying quackery is always a good thing. :)
    • Look into placebo a little more. You will find that a large portion of the effect isn't even "expected to feel better, felt better" but rather effects that are completely useless to the patient. Two big ones are reporting expectation (you expect me to feel better, so I'll say that I do) and the fact that most studies have other components (often general monitoring and support) which help both branches of the trial. Neither of those benefits anybody outside of the trial.
      • by narcc ( 412956 )

        You might want to look into placebo a little more. You'll find that they can produce very real, measurable, physiological effects. They can be harmful as well, often called the nocebo effect.

        Placebos work, which is why you need to subtract the placebo response in order to determine a drug's effectiveness. You might not like it, but that's reality.

    • Acupuncture might not be 'placebo'. There's an effect. However, the tricky bit is, the effect is not necessarily related to centuries old folk practice, and complex charts of acupuncture points and flow were not created following any sort of rigorous procedure. Folk medicine may or may not work, and when it does work it's not scientifically tested for proper dosage, which ailments it does work on, and so forth. The myth is that ancient people were godlike in their wisdom, but even if that were improbabl

    • Broken window fallacy isn't a great basis for an economy. We can retrain acupuncturist to be feng shui decorators for example.

  • Are there enough meta analysis of meta analysis papers yet to do a meta analysis on them?

    • That is one of the problems with modern scholarship. The original data can be dangerously poor, or incomplete, but the layers of meta-analysis are astonishingly vulnerable to bias. I'm afraid it's not merely a problem in the soft sciences: the "dark matter" proofs seem vulnerable to similar over-complex analysis of what is quite limited raw data.

    • Are there enough meta analysis of meta analysis papers yet to do a meta analysis on them?

      ooh!!!

      I know a nifty technique would could use to make a model to analyze the numbers and find out!

    • by hawk ( 1151 )

      >Are there enough meta analysis of meta analysis papers yet to do a meta analysis on them?

      metabe, metabe not. :)

  • Phenylephrine HCl works great for me, which makes me wonder whether these studies showing its ineffectiveness were done in a population that did not follow the dosage guidelines and took more than the recommended dosage, which feeds into a positive feedback loop of increasing doses vs increasing dose tolerance. Anyone who falls into this pattern will quickly find that the drug has little or no effect due to tolerance. This is a very well-known characteristic of decongestants, which is why I try to avoid th

    • You're one of the few people it works for.

      For most of us, it's as useful as a sugar pill. I tried it once, many years ago when they first put the real stuff behind the counter. It did absolutely nothing, I had to go back and be treated like a criminal to buy the (suddenly more expensive) pseudoephedrine.

    • by colfer ( 619105 )

      Interesting. I've noticed another feedback thing in pseudoephedrine, more congestion than I started with after going off it. And it has minor side effects systemically, some good, some bad. Low-key weird drug. So I use it sparingly. What I like to call psuedo-pseudoephedrine (phenylephrine) sounds like a good solution for you.

      Pseudoephedrine is still fairly easy to buy. You just show your license. You don't need a prescription, but can only buy x amount every three months. Some pharmacies have stopped carry

    • I had a doctor tell me once I can take nothing and feel better in about a week, or I can take cold pills and feel better in 5-7 days,
    • I wonder if it's not just the acidic effect which helps, with the difference in PH and titratable acidity being the determining factor rather than the supposed active compounds.

    • by Ichijo ( 607641 )

      Phenylephrine HCl doesn't work for me as a decongestant but as an antihistamine. To that end, it doesn't work as well as Benadryl (diphenhydramine HCl) or Nyquil, but it doesn't make me drowsy, and it plus a nasal rinse (Neti pot) works better than pseudoephedrine alone ever did.

    • by Megane ( 129182 )

      It's classic Actifed for me. I don't think they even make it any more because of the scare storm about making meth from PE (very much not the best way to make it), bit you can still get generics.

      Start with two Sudafeds worth of PE, then add some stuff called Triprolidine. [wikipedia.org] What you get will put me the fuck to sleep for four hours solid (after half an hour start delay), so I normally have to break them in half, which only makes my supply last longer. Lately I've started breaking the halves in half to see if

      • by Megane ( 129182 )
        And now I realize another annoyance of phenylephrine. It also can be abbreviated PE. I was referring to psuedoephedrine above, of course.
  • by chihowa ( 366380 ) on Friday December 22, 2023 @07:38AM (#64098513)

    This is what happens when law enforcement gets to interfere with our country's healthcare. The idea that an entire society has to suffer poorer healthcare because a minuscule fraction of the population will use a drug to have fun is something only authoritarian goons could dream up.

    The same situation is currently playing out with several ADHD drugs as we speak (mass shortages based on arbitrary DEA-imposed restrictions). It has also held back research into various psychedelic drugs as effective treatments for PTSD, treatment-resistant depression, and others.

    The DEA has got to go, but a good first start would be keeping them far away from our medicines and healthcare. The idea that we have to have an entire office of armed police with the sole aim of making sure that a small subset of the population can't get high or self-medicate is asinine.

    • It reminds me of being in grade school. First or second grade. Long time ago... Anyway, one of the kids did something stupid, the teacher got angry, and said that we would all be punished until the person who did the thing came forward. And I sat there thinking, "Why should I be punished because some other kid is being the problem?"

      Anyway, can pseudo be used to make meth or whatever? Sure. I'm sure it can. But I'm not making meth. I want to be able to breathe. Don't make life any harder on me, I'm not the p

    • I sincerely hope you are writing your elected officials making exactly this argument. Maybe if enough of us did, then we wouldn't have this drain on the taxpayers any more. No sarcasm implied whatsoever.
    • Someone has never had to live in a trailer park or weekly stay hotel with a few meth labs. Once they get to cooking, it's nonstop noxious fumes and jankers with bad teeth stealing everything in sight for another fix. No copper wires or cabling will be safe! If that's your idea of people "using a drug to have fun" then no thank you.

      • by chihowa ( 366380 )

        It doesn’t sound like fun to me, but what do you think is responsible for these jankers having to go to such lengths to get what would amount to a few bucks worth of product if it wasn’t illegal. It sounds like a medical problem, honestly. Once you get the cops involved, now you have two problems.

  • by cascadingstylesheet ( 140919 ) on Friday December 22, 2023 @07:52AM (#64098533) Journal

    Sure, could be true.

    But we've had mass "THING doesn't work at all!!" hysterias before.

    You may have noticed, for example, that antidepressants still exist. That's because they work. Ask the man on the street though, and he'll believe that they don't work, because oh noes meta analysis and lots of news stories.

    • by DarkVader ( 121278 ) on Friday December 22, 2023 @08:22AM (#64098581)

      Except that phenylephrine doesn't work.

      It was pushed on us during the meth panic. I only ever bought it once, because once was all I needed to know taking it was pointless.

      And big pharma knew it didn't work many years ago, a friend is a research scientist with one of them, and he not only agreed with me that it was useless, he knew why it didn't work. (I don't remember the explanation, I'm not that good with organic chemistry.) But of course they were making money with it, so there was no incentive for them to tell the FDA.

      • by piojo ( 995934 )

        Nasally it works. (Any why flood the whole body with a drug that's only needed in a bit of the nasal passages?)

        But I've read comments here that it works but the current dosage recommendation is wrong. I plan to test that later, but nasal decongestants work so well and quickly that pills are more for when you can't get the good stuff. (Warnings: you need to limit your usage to avoid rebound congestion, and oxymetazoline works but is a stimulant that may cause insomnia.)

      • by hawk ( 1151 )

        >I only ever bought it once, because once was all I needed to know taking it was pointless.

        this.

        pseudoephedrine is my idea of "wonder drug". It's generally their *only* relief available for either my allergies or sinus headaches.

        my wife bought the phenyl wannabe once, not knowing better--and it, quite spectacularly, did nothing.

        OK, it's actually #3 in effectiveness.

        #2. hot arid air. A car that's been sitting in the sun all day on a 110 degree day in vegas. Hop in and close the door quickly. Also the

    • The fact that phenylephrine doesn't work as a decongestant has been known since long before the pseudoephedrine ban. That's why it wasn't used as a decongestant! It's not a new drug.

    • Ask the man on the street though

      No thanks. I don't ask random people on the street about medical advice. That would be dumb.

  • by JBMcB ( 73720 )

    The FDA doesn't want to be responsible for anything any more.

    About 20 years ago they changed the way they monitor the safety of medical devices. Now, the onus of evaluating if a medical device is safe in the wild is on the manufacturer. The manufacturer has to collect all the data, interview doctors, and evaluate health care trends to see if their devices are safe. They have to file this paperwork with the FDA and, if the FDA decides they didn't do a good job or come to the correct conclusion, the manufactu

  • We've long known that phenylepherine doesn't work. It does a great job at raising some blood pressure in some people. As a decongestant? No. Aside from being one of the more onerous examples of drug panic stupidity, this kind of thing causes other problems. By stigmatizing pseudoephedrine, which is a safe and effective medication, people went off to using all sorts of other crap which wasn't. They silently replaced the active ingredient in medications across the board and kept the same product names, so mos

    • by piojo ( 995934 )

      Pseudoephedrine gave me heart palpitations, so I don't know why everyone seems to think it's so safe we don't need alternatives.

      • ...so I don't know why everyone seems to think it's so safe we don't need alternatives.

        That's because that ISN'T what "everyone seems to think". You've got that wrong and have not properly understood the complaint.

        Literally *NOBODY* said: "there should be no other decongestant options than pseudoephedrine" - that's just something you've made up.

        What people ARE saying is: "please don't replace actually effective medicines with ones we know DON'T work, especially for BS reasons".

        • by piojo ( 995934 )

          I'm sorry I didn't read all of your comment, and was operating on some different assumptions. I see how the situation with the branded medications must be frustrating and feels almost predatory. And if it's only 1% bioavailable orally, the replacement will do pretty much nothing. But I may be out of touch since I don't take combination drugs, but in my area I went to several pharmacies and couldn't buy phenylephrine. It seems that as a plain pill, it's already been supplanted (in my area, but presumably not

    • by HBI ( 10338492 )

      Doctor shopping is real. Addicts would prefer the medical version rather than the street fentanyl or alternatively emptying veterinary fentanyl patches with a needle.

      I'm not suggesting the DEA methodology actually gets results - most doctor shoppers go unpunished except for wrecking their bodies, and most also ultimately end up on the street drugs anyway. The prescription databases aren't even nationally unified, so the whole regimen has little point in the end if you have multiple states available to you

  • I tried them, They didn't work.
  • I've known for decades that oral phenylephrine does nothing. Anyone not susceptible to hypnotic suggestibility who has tried it has found the same thing.

  • Galling to think that people would be encouraged to sell the public drugs not known to work at all. Also, why are homeopathic things still being sold?

Keep up the good work! But please don't ask me to help.

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