4 ms·

A prescriber let slip to me at least once. Regarding SSRIs too. "Well, we don't really know how they work, but..." That's not science, that's a cargo cult.

faeriechangling 3y ago
Not really, you don't have to understand something to take advantage of it. My grandmother doesn't really understand how computers work but she still loves using her computer. Psychiatrists love SSRIs because they are efficacious (for a much smaller minority of those prescribed them than people realise), even when they're not more effective than placebo - placebos are actually pretty effective at treating issues. They're relatively cheap, easy to get patients who might be going through various issues to comply with the treatment, SSRI's being efficacious for the first few months after starting treatment is not that controversial, and that can allow you to monkey branch to more sustainable forms of treatment. The fact psychiatrists are prescribing drugs for a mental illness when they aren't aware of its mechanism of action is far from the worst sin of psychiatry. First off, the very notion that psychiatrists/doctors should gatekeep prescriptions in the first place being helpful isn't an evidence based practice, and how we define and diagnose mental illness in the first place is a Pandora's box of assumptions.
fylham 3y ago
Well given how complex the brain is, and how young neuroscience is, it’s no surprise that we haven’t unlocked deep knowledge about why psychopharmacological agents work. But granted the above, it isn’t prudent to wait decades for the brain to be understood before we try to help people struggling with mental health. If we can demonstrate that something is reasonably safe and makes a decent difference in helping someone’s life, shouldn’t we offer it to them (even if we don’t know on a deep level how it works)?
- NoZebra120vClip 3y ago
  > If Yes, if. We can, and we have, but instead the field has been usurped by junk science, and those who would dump industrial waste on us and into the water supply.
  - whats_a_quasar 3y ago
    Huh? What exactly are you claiming?
nom 3y ago
I have bad news for you, this is the case for many drugs. https://en.wikipedia.org/wiki/Category:Drugs_with_unknown_mechanisms_of_action https://en.wikipedia.org/wiki/Category:Drugs_with_unknown_me... We don't know how paracetamol works.
- gkhartman 3y ago
  That list seems pretty incomplete/sparse. It's pretty unsettling that paracetamol, as common as it is in modern medicine, would still lack a known mechanism of action. I wonder if it's just a hard question to answer, or something more boring like research cost vs benefit ratios etc.
  - jagraff 3y ago
    It is an extremely hard question to answer. Think about how hard it is to debug software, even though software is designed by humans, is intended to be readable by humans, and has tools to help us in analyzing it. Then think about how much harder it would be to understand a system that instead came about by billions of years of chance mutations building up to develop self reproducing systems that are not at all meant to be easily understood, and that follow much more complex rules (quantum mechanics) than binary computers do.
  - shtack 3y ago
    there’s a relevant xkcd, as usual: https://xkcd.com/2682/ https://xkcd.com/2682/
- retrac 3y ago
  There's no generally accepted theory for the mechanism of action of inhalational anaesthetics like xenon, which induces a deep coma, somehow, despite being almost chemically inert.
  - whats_a_quasar 3y ago
    My understanding for Xenon is that it's huge electron shell means that it has an induced dipole in the presence of other dipoles in the body. It then affects receptors with dipole-dipole bonds. I was also confused by Xenon working as an anesthetic, and found it interesting that it can interact with the body without forming chemical bonds. Doesn't work for the lighter noble gasses.
pests 3y ago
Drugs can be classed into two categories. Those we know the mechanism of action and those we just know what effects it produces. A lot of mental health meds fall into the latter category.
- pessimizer 3y ago
  There's a third class: drugs that were discovered because they caused an effect that was theorized to be related to the actual target by long-disproven ideas of how bodies worked, and that show little or no benefit to the target condition but are still prescribed as they have always been. We decided that seizures made people sane, created drugs and treatments to spark controlled seizures, then tried to make drugs that seemed similar but didn't cause tardive dyskinesia. Tardive dyskinesia was the only reason these drugs were ever even investigated, but the field somehow still moves forward like a racehorse without a head, claiming effects 10% above placebo.
hobs 3y ago
How things work and if they work are very different problems that science can help us solve. If you perform a double blind trial that throwing a brick at the back at someone's head will most likely cause a concussion or major injury you don't really have to understand the mechanism to get the result, just repeat the treatment.
whats_a_quasar 3y ago
But SSRIs do work. Experiment often proceeds theory. Uncertainty about the exact mechanism doesn't change the fact that SSRIs reduce symptoms of anxiety and major depression symptoms in many people. They have drastically improved my life and the lives of many family members and friends.
- pessimizer 3y ago
  > But SSRIs do work. This is not at all settled, and for the people who believe it wholly, the effects that are claimed are marginal. It's fine to talk about the benefits of SSRIs, although they may be controversial, but to use them as a basis for believing in other things is like 12 steps too far.
  - whats_a_quasar 3y ago
    > This is not at all settled. Yes, it is. > For the people who believe it wholly, the effects that are claimed are marginal No, the effects are not marginal. Research, the experience of basically all clinicians who prescribe antidepressants, and my personal experience all show they treat depression. For a given person, an SSRI may significantly relieve their symptoms, have a mild effect, or have no effect. Across the population, studies of SSRIs consistently show they work to treat major depression [1]. Every clinician I've met has observed SSRIs being effective. They see depression symptoms getting better when medication starts, and they observe relapses when medication stops. When I started taking Escitalopram, I stopped being depressed. When I stopped taking Escitalopram, I became depressed again. When I re-started Escitalopram, I stopped being depressed again. My grandfather had the same experience. When he went on Citalopram, he became calmer and less irritable than he'd ever been in his life. He stopped taking Citalopram for a few weeks, because of a physical illness that interrupted a prescription refill, and immediately slipped back into a depression. When he went back on Citalopram in the hospital, he was smiling and singing again two weeks later. [1] https://astralcodexten.substack.com/p/all-medications-are-insignificant https://astralcodexten.substack.com/p/all-medications-are-in... https://astralcodexten.substack.com/p/all-medications-are-insignificant https://astralcodexten.substack.com/p/all-medications-are-in...
BugsJustFindMe 3y ago
People are downvoting you, but I'm going to upvote you and respond carefully because I think there's an important lesson about language and science here. > That's not science, that's a cargo cult. Science deals completely and exclusively with modeling "if this then that". And the breakdown for "if this then that" depends on the current observability of the scale you're trying to describe. We don't know how gravity works, because we can't look inside gravity, we can only look at gravity's effects on other things, but we know that it does appear to work, and we believe that it works in the same way every time, and we can use observations and organized thinking to model gravity in a way that allows us to predict what will happen "if this". So we can safely say we don't know how gravity itself works, but we can also safely say that we do know the relationship between gravity and mass, because that's something we can observe. Likewise, we can safely say we don't know "how antipsychotics work inside the brain", but we can also safely say we do know "how antipsychotics work on populations", because populations are easily observed and inside the brain is not. Both use the word "how". The difference is what we're currently able to observe. This is a language problem, not a science problem. At an essential level, science can't answer how many things work, because the deeper into the unobserved you try to talk about (and the workings of the brain are still approximately 100% unobserved) "how", which is a question about things we can observe, becomes more and more a mis-use of the word "how" to talk about "why", which is a question about things we cannot observe, and science doesn't talk about things we cannot observe. It would only be cargo culting if the "but...", which I assume went on to say "...it appears to be beneficial for many people", were instead "and we haven't bothered to observe whether it helps anyone". But again I assume that's not how the sentence ended.
- s1artibartfast 3y ago
  I would add that there's infinite gradations to how and why. Answers for how range from the extremely simplistic: you put the pill in your mouth and swallow it, down to questions about the fundamental forces of the universe, and the nature of consciousness, neither of which are understood
  - BugsJustFindMe 3y ago
    That's certainly an important point, though I would argue that it's just a consequence of there being many different levels and directions of observation. "How does this pill work?" -> "You put it in your mouth" comes from observing at the level of your mouth, or alternately observing the intake process. It's not the most insightful detail to observe about the pill, but it's probably the most practically useful! You could of course put the pill somewhere else, and maybe it would work there too or maybe not (it probably depends on where exactly you put it).
Dylan16807 3y ago
We're still not entirely sure how gravity works.
Analemma_ 3y ago
That's not what "cargo cult" means. Quite ironically, you are cargo culting the term.
what-no-tests 3y ago
No, it's magical thinking. "Last time there was a storm, it stopped when I sacrificed a dog and danced in a circle. Let's try it again."
- jimmaswell 3y ago
  Then with a little scientific method, you soon realize storms and dogs are uncorrelated. Or you find out a drug seems to work even if you can't fully explain why.
  - deleted 3y ago
    [deleted]
- Mordisquitos 3y ago
  "Last season crops grew better on that field after the cows were allowed to grazed on it, but the field where we kept out the cows was as bad as always. Let's try letting cows graze on both fields." "What did we say about magical thinking?" "Sorry dad. Let's keep the cows off the field like we always did."
  - what-no-tests 3y ago
    If people were that good at noticing patterns, it wouldn't have taken Cortez arriving on the soil of the New World in order to bring the wheel to its inhabitants, who had been here 14,000 years and produced zero wheels.
chankstein38 3y ago
Last I heard we don't even know how anesthesia works fully. It's just kind of how medicine functions. I don't think it's bad. We're doing what we can to mitigate what we can while we figure out what the heck is actually happening.
oblib 3y ago
It's never been a secret that we don't know for sure how some of these anti-psychotic drugs work. It good to know there are folks working hard on finding out what's going on and ways to deal with psychosis. There's been some interesting work recently on how "gut bugs" might have a roll in this as well: https://www.psychologytoday.com/us/blog/balanced/202308/targeting-the-gut-in-the-treatment-of-mental-illness https://www.psychologytoday.com/us/blog/balanced/202308/targ...
thewataccount 3y ago
I have some bad news for you about Tylenol/Paracetamol.... The science is "We did many double blind studies on a large population and observed these effects to a degree statistically significant compared to placebo" We can reproduce the effects reliably, and the side effects are similarly predictable. We've also researched the pharmacokinetics to see what it's doing, but we don't necessarily understand how those changes cause it's effects. Just because we don't know exactly how it works, doesn't mean we didn't observe what the effects are. When the good effects out way the bad effects then it's a possible treatment. I'm not saying all studies are of quality, that there aren't unknown effects we haven't observed yet, that there aren't problems etc. What I'm saying is we have at least attempted to measure the effects and determine them to a statistically significant degree. tl;dr - If we've measured effects to a statistically significant degree - that is not a cargo cult. How many people understand the electrical wiring in their house yet use a light switch daily?
ShrigmaMale 3y ago
science is a mechanism for testing hypotheses. it may not be as medically rigorous as we want but modeling the complete receptor interactions and exactly what sorts and degrees of modulation happens as a result across the whole brain and body is really, really hard btw this is why i think the phrase "the science" as it relates to a pseudointellectual synonym for "the answer" needs to die
scns 3y ago
To tired to read all comments. After being prescribribeb SSRIs, i feel 60-70% less sexual pleasure. Another commenter here on HN reported the same.

faeriechangling 3y ago

Not really, you don't have to understand something to take advantage of it. My grandmother doesn't really understand how computers work but she still loves using her computer. Psychiatrists love SSRIs because they are efficacious (for a much smaller minority of those prescribed them than people realise), even when they're not more effective than placebo - placebos are actually pretty effective at treating issues. They're relatively cheap, easy to get patients who might be going through various issues to comply with the treatment, SSRI's being efficacious for the first few months after starting treatment is not that controversial, and that can allow you to monkey branch to more sustainable forms of treatment. The fact psychiatrists are prescribing drugs for a mental illness when they aren't aware of its mechanism of action is far from the worst sin of psychiatry. First off, the very notion that psychiatrists/doctors should gatekeep prescriptions in the first place being helpful isn't an evidence based practice, and how we define and diagnose mental illness in the first place is a Pandora's box of assumptions.

fylham 3y ago

Well given how complex the brain is, and how young neuroscience is, it’s no surprise that we haven’t unlocked deep knowledge about why psychopharmacological agents work. But granted the above, it isn’t prudent to wait decades for the brain to be understood before we try to help people struggling with mental health. If we can demonstrate that something is reasonably safe and makes a decent difference in helping someone’s life, shouldn’t we offer it to them (even if we don’t know on a deep level how it works)?

NoZebra120vClip 3y ago
> If Yes, if. We can, and we have, but instead the field has been usurped by junk science, and those who would dump industrial waste on us and into the water supply.
- whats_a_quasar 3y ago
  Huh? What exactly are you claiming?

nom 3y ago

I have bad news for you, this is the case for many drugs. https://en.wikipedia.org/wiki/Category:Drugs_with_unknown_mechanisms_of_action https://en.wikipedia.org/wiki/Category:Drugs_with_unknown_me... We don't know how paracetamol works.

gkhartman 3y ago
That list seems pretty incomplete/sparse. It's pretty unsettling that paracetamol, as common as it is in modern medicine, would still lack a known mechanism of action. I wonder if it's just a hard question to answer, or something more boring like research cost vs benefit ratios etc.
- jagraff 3y ago
  It is an extremely hard question to answer. Think about how hard it is to debug software, even though software is designed by humans, is intended to be readable by humans, and has tools to help us in analyzing it. Then think about how much harder it would be to understand a system that instead came about by billions of years of chance mutations building up to develop self reproducing systems that are not at all meant to be easily understood, and that follow much more complex rules (quantum mechanics) than binary computers do.
- shtack 3y ago
  there’s a relevant xkcd, as usual: https://xkcd.com/2682/ https://xkcd.com/2682/
retrac 3y ago
There's no generally accepted theory for the mechanism of action of inhalational anaesthetics like xenon, which induces a deep coma, somehow, despite being almost chemically inert.
- whats_a_quasar 3y ago
  My understanding for Xenon is that it's huge electron shell means that it has an induced dipole in the presence of other dipoles in the body. It then affects receptors with dipole-dipole bonds. I was also confused by Xenon working as an anesthetic, and found it interesting that it can interact with the body without forming chemical bonds. Doesn't work for the lighter noble gasses.

pests 3y ago

Drugs can be classed into two categories. Those we know the mechanism of action and those we just know what effects it produces. A lot of mental health meds fall into the latter category.

pessimizer 3y ago
There's a third class: drugs that were discovered because they caused an effect that was theorized to be related to the actual target by long-disproven ideas of how bodies worked, and that show little or no benefit to the target condition but are still prescribed as they have always been. We decided that seizures made people sane, created drugs and treatments to spark controlled seizures, then tried to make drugs that seemed similar but didn't cause tardive dyskinesia. Tardive dyskinesia was the only reason these drugs were ever even investigated, but the field somehow still moves forward like a racehorse without a head, claiming effects 10% above placebo.

hobs 3y ago

How things work and if they work are very different problems that science can help us solve. If you perform a double blind trial that throwing a brick at the back at someone's head will most likely cause a concussion or major injury you don't really have to understand the mechanism to get the result, just repeat the treatment.

whats_a_quasar 3y ago

But SSRIs do work. Experiment often proceeds theory. Uncertainty about the exact mechanism doesn't change the fact that SSRIs reduce symptoms of anxiety and major depression symptoms in many people. They have drastically improved my life and the lives of many family members and friends.

pessimizer 3y ago
> But SSRIs do work. This is not at all settled, and for the people who believe it wholly, the effects that are claimed are marginal. It's fine to talk about the benefits of SSRIs, although they may be controversial, but to use them as a basis for believing in other things is like 12 steps too far.
- whats_a_quasar 3y ago
  > This is not at all settled. Yes, it is. > For the people who believe it wholly, the effects that are claimed are marginal No, the effects are not marginal. Research, the experience of basically all clinicians who prescribe antidepressants, and my personal experience all show they treat depression. For a given person, an SSRI may significantly relieve their symptoms, have a mild effect, or have no effect. Across the population, studies of SSRIs consistently show they work to treat major depression [1]. Every clinician I've met has observed SSRIs being effective. They see depression symptoms getting better when medication starts, and they observe relapses when medication stops. When I started taking Escitalopram, I stopped being depressed. When I stopped taking Escitalopram, I became depressed again. When I re-started Escitalopram, I stopped being depressed again. My grandfather had the same experience. When he went on Citalopram, he became calmer and less irritable than he'd ever been in his life. He stopped taking Citalopram for a few weeks, because of a physical illness that interrupted a prescription refill, and immediately slipped back into a depression. When he went back on Citalopram in the hospital, he was smiling and singing again two weeks later. [1] https://astralcodexten.substack.com/p/all-medications-are-insignificant https://astralcodexten.substack.com/p/all-medications-are-in... https://astralcodexten.substack.com/p/all-medications-are-insignificant https://astralcodexten.substack.com/p/all-medications-are-in...

BugsJustFindMe 3y ago

People are downvoting you, but I'm going to upvote you and respond carefully because I think there's an important lesson about language and science here. > That's not science, that's a cargo cult. Science deals completely and exclusively with modeling "if this then that". And the breakdown for "if this then that" depends on the current observability of the scale you're trying to describe. We don't know how gravity works, because we can't look inside gravity, we can only look at gravity's effects on other things, but we know that it does appear to work, and we believe that it works in the same way every time, and we can use observations and organized thinking to model gravity in a way that allows us to predict what will happen "if this". So we can safely say we don't know how gravity itself works, but we can also safely say that we do know the relationship between gravity and mass, because that's something we can observe. Likewise, we can safely say we don't know "how antipsychotics work inside the brain", but we can also safely say we do know "how antipsychotics work on populations", because populations are easily observed and inside the brain is not. Both use the word "how". The difference is what we're currently able to observe. This is a language problem, not a science problem. At an essential level, science can't answer how many things work, because the deeper into the unobserved you try to talk about (and the workings of the brain are still approximately 100% unobserved) "how", which is a question about things we can observe, becomes more and more a mis-use of the word "how" to talk about "why", which is a question about things we cannot observe, and science doesn't talk about things we cannot observe. It would only be cargo culting if the "but...", which I assume went on to say "...it appears to be beneficial for many people", were instead "and we haven't bothered to observe whether it helps anyone". But again I assume that's not how the sentence ended.

s1artibartfast 3y ago
I would add that there's infinite gradations to how and why. Answers for how range from the extremely simplistic: you put the pill in your mouth and swallow it, down to questions about the fundamental forces of the universe, and the nature of consciousness, neither of which are understood
- BugsJustFindMe 3y ago
  That's certainly an important point, though I would argue that it's just a consequence of there being many different levels and directions of observation. "How does this pill work?" -> "You put it in your mouth" comes from observing at the level of your mouth, or alternately observing the intake process. It's not the most insightful detail to observe about the pill, but it's probably the most practically useful! You could of course put the pill somewhere else, and maybe it would work there too or maybe not (it probably depends on where exactly you put it).

Dylan16807 3y ago

We're still not entirely sure how gravity works.

Analemma_ 3y ago

That's not what "cargo cult" means. Quite ironically, you are cargo culting the term.

what-no-tests 3y ago

No, it's magical thinking. "Last time there was a storm, it stopped when I sacrificed a dog and danced in a circle. Let's try it again."

jimmaswell 3y ago
Then with a little scientific method, you soon realize storms and dogs are uncorrelated. Or you find out a drug seems to work even if you can't fully explain why.
- deleted 3y ago
  [deleted]
Mordisquitos 3y ago
"Last season crops grew better on that field after the cows were allowed to grazed on it, but the field where we kept out the cows was as bad as always. Let's try letting cows graze on both fields." "What did we say about magical thinking?" "Sorry dad. Let's keep the cows off the field like we always did."
- what-no-tests 3y ago
  If people were that good at noticing patterns, it wouldn't have taken Cortez arriving on the soil of the New World in order to bring the wheel to its inhabitants, who had been here 14,000 years and produced zero wheels.

chankstein38 3y ago

Last I heard we don't even know how anesthesia works fully. It's just kind of how medicine functions. I don't think it's bad. We're doing what we can to mitigate what we can while we figure out what the heck is actually happening.

oblib 3y ago

It's never been a secret that we don't know for sure how some of these anti-psychotic drugs work. It good to know there are folks working hard on finding out what's going on and ways to deal with psychosis. There's been some interesting work recently on how "gut bugs" might have a roll in this as well: https://www.psychologytoday.com/us/blog/balanced/202308/targeting-the-gut-in-the-treatment-of-mental-illness https://www.psychologytoday.com/us/blog/balanced/202308/targ...

thewataccount 3y ago

I have some bad news for you about Tylenol/Paracetamol.... The science is "We did many double blind studies on a large population and observed these effects to a degree statistically significant compared to placebo" We can reproduce the effects reliably, and the side effects are similarly predictable. We've also researched the pharmacokinetics to see what it's doing, but we don't necessarily understand how those changes cause it's effects. Just because we don't know exactly how it works, doesn't mean we didn't observe what the effects are. When the good effects out way the bad effects then it's a possible treatment. I'm not saying all studies are of quality, that there aren't unknown effects we haven't observed yet, that there aren't problems etc. What I'm saying is we have at least attempted to measure the effects and determine them to a statistically significant degree. tl;dr - If we've measured effects to a statistically significant degree - that is not a cargo cult. How many people understand the electrical wiring in their house yet use a light switch daily?

ShrigmaMale 3y ago

science is a mechanism for testing hypotheses. it may not be as medically rigorous as we want but modeling the complete receptor interactions and exactly what sorts and degrees of modulation happens as a result across the whole brain and body is really, really hard btw this is why i think the phrase "the science" as it relates to a pseudointellectual synonym for "the answer" needs to die

scns 3y ago

To tired to read all comments. After being prescribribeb SSRIs, i feel 60-70% less sexual pleasure. Another commenter here on HN reported the same.