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.
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.
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
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.
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?
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.
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.
Usually they fuck with something like extra sweating or a little trouble sleeping. Severe side effects are very rare, they are widely used because they are so well tolerated. My own anecdote is: most elderly people should be on Cymbalta because they live in so much pain. I've been offered Prozac for chronic pain, I bet it would help them too. Boomers suffer needlessly. Get them on Prozac, please.
The point is that SSRIs (and reuptake inhibitors in general) are extremely crude. It's like using a dull rock instead of a scalpel, or full body radiation to remove a mole on your hand. They have a lot of secondary and tertiary effects we don't understand, nor do we truly understand the primary mechanism.
We don't know exactly what these drugs do to the body, how they do it, or what the consequences really are.
They have good outcomes for a small section of the population and that's about all we know.
One could argue that over-prescription of such a poorly understood class of drug is far more harmful.
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.
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.
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.
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.
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.