5 ms·

When I went into residency, my attending once described any drug acting on reuptake (be it antagonistically, agonistic, or in a bifurcated model) as the medical

When I went into residency, my attending once described any drug acting on reuptake (be it antagonistically, agonistic, or in a bifurcated model) as the medical equivalency of noticing your car is low on oil and, in response, pouring a few dozen liters of the stuff over the engine block. Some gets to where it needs to be, the rest gunks up the engine on the outside and in places it shouldn't be. Almost any drug acting on 5HT (fk acts on 2C), acts on other receptors as well. Fk acts on α1, M1-4, and many more, it's not very selective. A venerable bucket of oil, indeed. This is, what also causes Long-QT, feeding disorders, diarrhea, shorter pregnancies, dry mouth, sexual dysfunction, and more. Sure, dropping such a bucket of oil can also, via inflammatory pathways, elicit IL-10 activation and, more importantly, act against hypertriglyceridemia. But that should not be sold as a solution to a problem. Again, to stay with contrived comparisons, if I load the boot of a car with C4, I am sure that some parts of the car will reach more than the car's stated maximum speed. But that's not a desirabe outcome. As a last ditch, I'd consider it. But "preventatively" as suggested... that's a far, far, reach.

cj 2y ago
After reading your comment, I was wondering "why do this study in the first place" if researchers are just pouring oil on an engine. The last sentence basically says that it's too difficult to get new drugs approved, so instead let's try to find new benefits of already widespread drugs. I suppose it's better to pour oil on an engine than to have no oil at all. > One of the most cost-effective and quickest strategies to develop treatment strategies is repurposing already approved drugs for new conditions. Our study provides sufficient rationale to further explore the therapeutic uses of SSRIs during infection and to reveal new and exciting immunometabolic targets during sepsis.
- rjurney 2y ago
  His comment isn't a medical opinion. It's a sarcastic anecdote.
rjurney 2y ago
Sorry, what does this have to do with the study? Obviously reuptake inhibitors save many lives and you're acting like they're all unusable. As a doctor, isn't this irresponsible?
- H8crilA 2y ago
  He says that a) yes there are many receptors which will be triggered by the same drug at the same time, so it can have a variety of effects, b) it's possibly not worth it to take it as a preventive measure. That doesn't mean he says it shouldn't be taken to cure or at least manage debilitating disorders like depression. Cost vs benefit. The discussion of costs/risks of treatments is usually what's missing in the casual conversations about drugs. Ketamine or psylocybin are probably the best examples in the tech community, yes they can sometimes cure a depression, or at least suppress it for a while, but they can also cause psychosis (and other non-psychiatric symptoms), so they are used only after safer options fail. Although I'm not sure I get the concern here, sepsis is very life threatening, so paying SNRI-level risk for prevention doesn't seem like an outright bad idea. Unless the idea would be for random people to start using this drug just in case they get stabbed and go septic - then I would say this is not a good idea. But I don't think this is what the paper describes.
  - rjurney 2y ago
    I just object to the use of anecdotes on the internet from actual doctors.
- forgetfreeman 2y ago
  That wasn't my takeaway at all. As someone who's been on the receiving end of various SSRIs for big chunks of my adult life their analogy seems pretty on-brand compared to the experience of taking SSRIs. They fuck with so many things that aren't the problem at hand it beggars belief. Anyway, if anything my takeaway was confirmation of my suspicion that SSRIs are the polar opposite of targeted therapeutics.
  - philjohn 2y ago
Lerc 2y ago
I think the analogy would work better if you had a couple of iron filings with the design of the engine block imprinted on it, then you constructed the engine by pouring buckets of stuff in the right proportions at the right time until the iron filings formed a working engine. If such an engine existed, perhaps it might be more amenable to refilling its oil in such circumstances.
herniatedeel 2y ago
I get that fluoxetine, a relatively old SSRI is a dirty drug, but aren't newer serotonin modulators much cleaner? E.g., vilazodone, vortioxetine, and even old-fashioned Escitalopram (lexapro)? My understanding is that escitalopram has pretty low binding affinity for other receptors than SERT.
- AStonesThrow 2y ago
  https://lyrics.lyricfind.com/lyrics/weird-al-yankovic-i-want-a-new-duck https://lyrics.lyricfind.com/lyrics/weird-al-yankovic-i-want...
- spoonfeeder006 2y ago
  But serotonin is active in many aspects of the body's physiology no? So just because it may not act on other classes of receptors, it still has wide ranging impacts. There are many kinds of SERT receptors, as they mentioned, Fk isn't all that selective about it
- alsoforgotmypwd 2y ago
  Fuck vilazadone and vortioxetine with 500kV. That shit gave me seizures, zaps, and myoclonus. Fluoxetine made my mom murderously psychotic. Paroxetine gave me immediate serotonin syndrome. The truth is most psychiatrists are unscientific shamans who don't measure or analyze the organ or systems they're supposedly treating. The only thing I've found tolerable from more than a dozen medications has been mirtazapine. All SSRIs I've tried were of marginal benefit with terrible side-effects.
a-dub 2y ago
would have been interesting if they had constructed a temporal loading dose response curve which could support a prophylactic protocol for emergency or otherwise high risk hospital admissions.
AStonesThrow 2y ago
> Long-QT, feeding disorders, diarrhea, shorter pregnancies, dry mouth, sexual dysfunction By design, these effects are features, not bugs, when experienced by the mentally ill. It's a tangible, temporal mortification of the flesh beyond mere incarceration! Moreover, and effective deterrent against procreation, longevity, frugality, temprance, , and/or straying more than 5 minutes' Naruto Run from their own bathroom facilities. It's considered immoral for Christians to sterilize themselves... but it's a civic virtue, and courageousness to feel oneself growing more impotent with successive phases of the Moon.

cj 2y ago

After reading your comment, I was wondering "why do this study in the first place" if researchers are just pouring oil on an engine. The last sentence basically says that it's too difficult to get new drugs approved, so instead let's try to find new benefits of already widespread drugs. I suppose it's better to pour oil on an engine than to have no oil at all. > One of the most cost-effective and quickest strategies to develop treatment strategies is repurposing already approved drugs for new conditions. Our study provides sufficient rationale to further explore the therapeutic uses of SSRIs during infection and to reveal new and exciting immunometabolic targets during sepsis.

rjurney 2y ago
His comment isn't a medical opinion. It's a sarcastic anecdote.

rjurney 2y ago

Sorry, what does this have to do with the study? Obviously reuptake inhibitors save many lives and you're acting like they're all unusable. As a doctor, isn't this irresponsible?

H8crilA 2y ago
He says that a) yes there are many receptors which will be triggered by the same drug at the same time, so it can have a variety of effects, b) it's possibly not worth it to take it as a preventive measure. That doesn't mean he says it shouldn't be taken to cure or at least manage debilitating disorders like depression. Cost vs benefit. The discussion of costs/risks of treatments is usually what's missing in the casual conversations about drugs. Ketamine or psylocybin are probably the best examples in the tech community, yes they can sometimes cure a depression, or at least suppress it for a while, but they can also cause psychosis (and other non-psychiatric symptoms), so they are used only after safer options fail. Although I'm not sure I get the concern here, sepsis is very life threatening, so paying SNRI-level risk for prevention doesn't seem like an outright bad idea. Unless the idea would be for random people to start using this drug just in case they get stabbed and go septic - then I would say this is not a good idea. But I don't think this is what the paper describes.
- rjurney 2y ago
  I just object to the use of anecdotes on the internet from actual doctors.
forgetfreeman 2y ago
That wasn't my takeaway at all. As someone who's been on the receiving end of various SSRIs for big chunks of my adult life their analogy seems pretty on-brand compared to the experience of taking SSRIs. They fuck with so many things that aren't the problem at hand it beggars belief. Anyway, if anything my takeaway was confirmation of my suspicion that SSRIs are the polar opposite of targeted therapeutics.
- philjohn 2y ago

Lerc 2y ago

I think the analogy would work better if you had a couple of iron filings with the design of the engine block imprinted on it, then you constructed the engine by pouring buckets of stuff in the right proportions at the right time until the iron filings formed a working engine. If such an engine existed, perhaps it might be more amenable to refilling its oil in such circumstances.

herniatedeel 2y ago

I get that fluoxetine, a relatively old SSRI is a dirty drug, but aren't newer serotonin modulators much cleaner? E.g., vilazodone, vortioxetine, and even old-fashioned Escitalopram (lexapro)? My understanding is that escitalopram has pretty low binding affinity for other receptors than SERT.

AStonesThrow 2y ago
https://lyrics.lyricfind.com/lyrics/weird-al-yankovic-i-want-a-new-duck https://lyrics.lyricfind.com/lyrics/weird-al-yankovic-i-want...
spoonfeeder006 2y ago
But serotonin is active in many aspects of the body's physiology no? So just because it may not act on other classes of receptors, it still has wide ranging impacts. There are many kinds of SERT receptors, as they mentioned, Fk isn't all that selective about it
alsoforgotmypwd 2y ago
Fuck vilazadone and vortioxetine with 500kV. That shit gave me seizures, zaps, and myoclonus. Fluoxetine made my mom murderously psychotic. Paroxetine gave me immediate serotonin syndrome. The truth is most psychiatrists are unscientific shamans who don't measure or analyze the organ or systems they're supposedly treating. The only thing I've found tolerable from more than a dozen medications has been mirtazapine. All SSRIs I've tried were of marginal benefit with terrible side-effects.

a-dub 2y ago

would have been interesting if they had constructed a temporal loading dose response curve which could support a prophylactic protocol for emergency or otherwise high risk hospital admissions.

AStonesThrow 2y ago

> Long-QT, feeding disorders, diarrhea, shorter pregnancies, dry mouth, sexual dysfunction By design, these effects are features, not bugs, when experienced by the mentally ill. It's a tangible, temporal mortification of the flesh beyond mere incarceration! Moreover, and effective deterrent against procreation, longevity, frugality, temprance, , and/or straying more than 5 minutes' Naruto Run from their own bathroom facilities. It's considered immoral for Christians to sterilize themselves... but it's a civic virtue, and courageousness to feel oneself growing more impotent with successive phases of the Moon.