Fluoxetine promotes metabolic defenses to protect from sepsis-induced lethality

https://www.science.org/doi/10.1126/sciadv.adu4034

by bookofjoe • 1 year ago

148 90 1 year ago

A recent study published in Science Advances reveals that fluoxetine, a commonly prescribed antidepressant, offers protective benefits against sepsis. The research demonstrates that fluoxetine enhances interleukin-10 (IL-10)–dependent metabolic defenses, leading to improved survival rates in sepsis-induced disease models. This protective effect is achieved through multiple mechanisms, including antimicrobial properties and modulation of inflammatory responses. The findings suggest that fluoxetine's anti-inflammatory and metabolic effects could be harnessed as a therapeutic strategy for sepsis.

Sepsis is a life-threatening condition that occurs when the body's response to an infection goes out of control, leading to widespread inflammation, tissue damage, and organ failure. It happens when the immune system, instead of fighting off the infection, starts attacking the body's own tissues.

Me000• 1 year ago

How would this effect gut bacteria?

meindnoch• 1 year ago

Gut bacteria will be happy, because their host didn't die from sepsis.

short_sells_poo• 1 year ago

You are technically correct (the best kind of correct), but I guess parent was asking whether this has any anti-bacterial side effects that might affect the gut flora. I'm wondering about this as well. The drug in question isn't an anti-biotic per-se, it doesn't help fight sepsis by making your body even more indiscriminately angry at bacteria - quite the opposite. Based on that, my suspicion is that the gut flora would not be affected directly, and would be happy on the basis of the host itself surviving the sepsis.

metalman• 1 year ago

gut bacteria operate under the assumption that even if there host dies, in very many cases the host will be the victim of a preditor or a scavenger, and just hitches a ride up or down.the food chain, perfectly happy taking 100 bilion to to 1 odds on making it to the next perfect host bah!, its not even the sort of thing even worth thinking about going into suspended animaton for edit: on further consideration ,the situation is actauly reversed, our flora do survive us, but we will die without them, and they have other, rather gross means of survival, by ...raising the dead, literaly in the case of corpses in.the water, due to there continued activity, bloating a dead body wherapon they escape useing a balisic method, on decompression.

shadowgovt4• 1 year ago

The mutualism of microorganisms and humans is a fascinating and relatively new sphere of research. One such space is the family of antibacterial (and antiviral) viruses that have apparently evolved into a mutualistic relationship with humans: their development and proclivity is tied to their hosts (they spread by direct placental diffusion from mother-to-fetus, or by milk, they're too fragile to survive in the external environment, and since humans eating humans is rare they don't have other avenues) and so they actually have features that attack harmful bacteria, attack and disrupt harmful viruses, or generate immune-system antagonistic chemical signals to attract our defenses to incoming infections.

They flew under the radar all this time because they're viruses; in general, the only viruses we're aware of in humans are the ones that cause harmful symptoms because actually visualizing the little bastards requires busting out the ol' electron microscope, so if they don't give us a reason to look we aren't looking!

jgalt212• 1 year ago

Here's a primer on the brain - gut connection. It's well established, but maybe not well understood.

https://www.hopkinsmedicine.org/health/wellness-and-preventi...

shadowgovt4• 1 year ago

There has, apparently, been some research on this, but (IANADoctor) it doesn't look conclusive.

https://pmc.ncbi.nlm.nih.gov/articles/PMC6330042/ did mouse trials of fluoxetine and then checked the gut microbiome; they did find some changes in groups known to correlate with regulation of body mass. But, this is (a) mouse models and (b) a long string of correlations with (to my knowledge) no actual causal understanding.

world2vec• 1 year ago

Some wikipedia context for this SSRI: "Fluoxetine, sold under the brand name Prozac, among others, is an antidepressant medication of the selective serotonin reuptake inhibitor class used for the treatment of major depressive disorder, anxiety, obsessive–compulsive disorder, panic disorder, premenstrual dysphoric disorder, and bulimia nervosa."

westurner• 1 year ago

Fluoxetine also appears to increase plasticity in the adult visual cortex, which can reduce monocular dominance. https://www.google.com/search?q=fluoxetine+plasticity+visual...

gradientsrneat• 1 year ago

Yep! And also psychosis (although generally not as the sole treatment).

Regarding premenstrual dysphoric disorder, a common treatment is to take birth control alongside an SSRI. Coincidentally, the current US federal government wants to ban both of those.

We still don't really know how most brain meds treat mental health issues, but most brain meds have far-reaching effects from the brain to the vascular system. So, a certain single medication may be used to treat both a mental health issue and a blood pressure issue.

jfengel• 1 year ago

I've been taking fluoxetine for several years and haven't died of sepsis. So that's one more data point in its favor.

saretup• 1 year ago

Now let’s hear from some dead people for balance.

fny• 1 year ago

Much salt: “fluoxetine pretreatment” “in a mouse model of sepsis.”

I’d be interested to see how this holds up in EHR data with the caveat that anyone with mental health issues likely has a million confounders.

I’m not even sure how this would be implemented in practice: at what point would patients be given SSRIs?

criddell• 1 year ago

Are there any signals that a person may be in danger of developing sepsis? If so, wouldn't that be the time to consider prescribing fluoxetine?

readthenotes1• 1 year ago

Apparently 15% of cases start in hospital so that would be one signal

https://www.verywellhealth.com/sepsis-while-hospitalized-858...

cogman102• 1 year ago

Yeah, seems like an easyish study to do. "Does EHR data show that patients on Prozac have a lower mortality rate from sepsis than the general population."

I’m not even sure how this would be implemented in practice: at what point would patients be given SSRIs?

Perhaps right before and after a surgery when infection is possible?

BobbyJo2• 1 year ago

Fluoxetine has an insanely long half life, and your brain is sensitive to its affects. Not really a viable option for acute treatment.

yosito• 1 year ago

In other words, "Study in mice suggests that taking Prozac might make you less vulnerable to sepsis. Further study needed."

jasongill2• 1 year ago

This article is timely - I just returned home yesterday from the funeral of a very close friend who died of sepsis. He was told at the ER that he just needed to go home and rest and that his stomach pain was likely a colitis flare-up.

I wonder if there will ever be a "rescue treatment" for sepsis that is based on this research. Lets hope so.

winocm• 1 year ago

My condolences.

I had SIRS/sepsis once and it really is a harrowing experience. It really changed me forever and as a bonus, if not to add insult to injury, my hair now falls out and barely grows. Wouldn't wish it on my worst enemy.

igor47• 1 year ago

I'm sorry. The same thing happened to a very close friend of mine. Sepsis is a bitch, and also I miss my friend all the time. I hope you have a community to support you in grief.

balderdash• 1 year ago

This company https://cytovale.com/ has developed a diagnostic tool for sepsis, while not a cure it hopefully would make cases like your friend’s less likely

jmort• 1 year ago

Also https://inflammatix.com/

zeagle3• 1 year ago

A lot of drugs and efforts to treat sepsis/SIRS with inflammation have fizzled in trial. Tocilizumab, JAK inhibitors, and particaularly dexamethasone with its low NNT in COVID were interesting ones and suggest there is something to it but a complicated issue.

Pxtl2• 1 year ago

Its horrifying how many stories sound like that, like the recent story woman who got parasitic worms from Hawaiian food that crept upwards from her legs gradually causing pain until they made it to her brain and only then the cognitive impairment made doctors take her seriously. She kept getting sent home too.

It's infuriating how many problems in our lives are met with a shrug.

edit: I'm a jerk, I forgot we were talking about somebody close to you. I'm sorry about your friend and I hope you're doing okay.

JumpCrisscross• 1 year ago

It's infuriating how many problems in our lives are met with a shrug

If you know anyone in medicine you know they are swamped by hypochondriacs, frauds and crazies. Absent clear diagnostic criteria--or a person privately funding the search costs, with time and money--it’s infeasible to expect a collectively-funded system to explore every potential case like an episode of House MD.

medimikka2• 1 year ago

Rescue treatments are symptomatic. Which makes a lot of sense, if you consider what (medically) constitutes "sepsis."

Any ED resident on their first week on the job should know how to diagnose sepsis: Temp >38°C (100.4°F) or <36°C (96.8°F), Heart rate >90, Respiratory rate >20 or PaCO₂ <32 mm Hg, WBC >12,000/mm³, <4,000/mm³, or >10% bands, Infection (suspected or present).

Double down on the blood work, take liquor, empirically give antibiotics (less and less useful, given resistances), drop temperature (paracetamol), add fluids (drops heart rate, ups blood pressure), wait for labs.

It's not hard, and I am so very sorry someone with sepsis signs was sent home. Sepsis is also a fast bastard. Meaning, from pathogen entering the blood stream to organ damage and conclusively death can be less than half an hour. That's the ones we can't catch. The guy with the ulcer, the person who injects things, the girl who didn't see a dentist about her developing abscess, the man who stopped his HIV meds... that's the ones I didn't in the past three weeks. I got them too late, or didn't see them until the ambulance unloaded a dead person.

Sepsis is a bitch. A total and utter bad player, something we drill into every resident from day one. Sometimes Mrs. Goodforall comes in with a light chest tightness and leaves on a hearse, sometimes Mr. Bluebird presents with nausea and crashes into a full on septic shock minutes later. Any one of those I can prevent, I will. I am, however, not God. Just a ED jockey with an infectious disease background. I'm probably the best hope my patients have, which isn't much, but it's something.

Madmallard• 1 year ago

What about the research surrounding high dose vit C, thiamine, dexamethasone or whatever that concoction was?

jasongill2• 1 year ago

Thank you; yes, he had a clinical history of colitis and other stomach issues, and had visited the ER due to abdominal pain over a weekend. On Tuesday he collapsed at home and was gone. I don't know what transpired with the doctor (and didn't want to pry too much with the grieving family) but it sounds like it was just missed or his symptoms misunderstood. I heard grumblings that the doctor was at fault but I don't fault them - things just happen and while it is sad, it just happens.

shadowgovt4• 1 year ago

If I understand correctly, this is one of those laws-of-exponents things that humans tend to have bad intuition for, right?

Bacteria growth, unchecked, is exponential. The only reason we stay a coherent organism at all in this crazy world of trillions of other organisms is that our immune system checks the hell out of bacteria growth.

... but when that's no longer possible, when the body goes from being a hostile growth environment to food... enterococcus faecalis has a doubling time of 18 minutes. One such cell, with completely-unchecked reproduction, would produce a number of itself to rival the cell-count of the entire body in only 10 hours, and it takes way less than 30 trillion enterococcus to kill a person.

FollowingTheDao5• 1 year ago

This is great because I am a huge believer that the immune system is at the core of many, if not all, mood disorders and maybe they will start looking at immunoneurology to start finally curing mood disorders. For example, we know that stress effects the immune system by lowering T Cells, and we know that stress makes people depressed, so would it not follow that lower T Cells makes people depressed? (T Cells make IL10)

Prozac makes me manic in a heart beat, literally one 10mg tablet (I have Bipolar Disorder) and they find higher levels of IL-10 in people with Bipolar.

https://pmc.ncbi.nlm.nih.gov/articles/PMC10357918/

And IL-10 increases serotonin activity as well:

https://pubmed.ncbi.nlm.nih.gov/23410504/

So we should assume that lower IL10 could be a metabolic marker for depression.

kerkeslager4• 1 year ago

This is great because I am a huge believer that the immune system is at the core of many, if not all, mood disorders and maybe they will start looking at immunoneurology to start finally curing mood disorders.

Christ, please stop talking about science if your approach is going to be "I'm a huge believer in this hypothesis so any research which supports that hypothesis is great". We don't need more lunacy in science discourse.

"The immune system is at the core of some mood disorders" is a reasonable hypothesis which is quite possibly true, given what we know. It certainly warrants more research, but I haven't seen anything conclusive enough to justify being "a huge believer".

"The immune system is at the core of all mood disorders" is an actually bad hypothesis which untestable.

For example, we know that stress effects the immune system by lowering T Cells, and we know that stress makes people depressed, so would it not follow that lower T Cells makes people depressed? (T Cells make IL10)

No, that does not follow. You're literally describing an A -> B, A -> C situation, which does not imply that B -> C. This is very, very basic causality reasoning you're screwing up here.

Less confidence/arrogance/belief and more "maybe" and "possibly" would do you well here.

FollowingTheDao5• 1 year ago

What do I mean by "I am a huge believer that the immune system is at the core of many, if not all, mood disorders"?

It means i think this is the direction research should take.

It means if people have mood disorders they should see an immunologist first, becasue this is how we can find out right now if it is true. (Many people with Lupus do not know they had Lupus and they were institutionalized with neuropsychiatric lupus and never got the help they needed. My mother was one of them. And see: https://www.youtube.com/watch?v=SXFX6OnSlng

That is the suffering those of us with immune issues have to put up with.

Does it mean I just want science to prove my belief correct? Of course not. What you need to do is stop being so overly dramatic. What I do believe is more and more research is pointing to Neuroimmunology as the basis for most mental illnesses. Which means I am excited.

https://pmc.ncbi.nlm.nih.gov/articles/PMC6693968/

https://onlinelibrary.wiley.com/doi/abs/10.1111/cen3.12639

No, that does not follow. You're literally describing an A -> B, A -> C situation, which does not imply that B -> C.

Of course, yes, correlation is not causation until it is proven. But absence of evidence is not evidence of absence.

For eff sake, I was just excited and not I had to waste my time explaining this to you and you ruined everything.

But let me tell you a story. Both times I caught COVID I had the worst psychosis of my life. And when I a sick with anything, there goes my mood as well. So if that does not tell you the immune system effects mental illness, what will?

I mean, to me it seems stupid that people would disagree that the immune system causes mood changes. Who feels happy when they have the flu? And if you knew anything about the tryptophan -> Kynurenine/serotonin pathway you would be even more excited about this discovery.

https://www.researchgate.net/figure/The-kynurenine-pathway-T...

If you do not get excited, what kind of scientists are you? The most boring and uncreative kind I would say.

passive• 1 year ago

My kid just went on this for anxierty a few weeks ago, happy to hear to has some side benefits.

goda90• 1 year ago

I wonder if this effect can also contribute to new allergies. My dog is on fluoxetine for anxiety. She also started having intermittent issues with hot spots and ear infections at some point after we started the fluoxetine. We have her on apoquel for allergies now, which is a steroid that impacts the immune system so she's getting double whammy impacts.

AStonesThrow5• 1 year ago

have you considered dialysis and chemotherapy, or space tourism

myrloc2• 1 year ago

I was just put on 6 weeks of antibiotics (ampicillin and ceftriaxone) for sepsis.

I thought I was coming down with an annual bug (so did the docs). 3 days after going into an urgent care where I was told I was negative for flu and covid, I went to the ER, where they drew blood. All 4 blood cultures returned positive for enterococcus faecalis.

The bacteria is very common in the intestines, but it's not clear (and probably never will be) how it made it into my bloodstream. Their best guess is inflammation in my gut allowing it to "leak" into the blood. This is after CT and ultrasounds of the abdomen.

29 years of no sepsis then.. random sepsis diagnosis!

zeagle3• 1 year ago

Glad you are OK. I am not your internist (/IANAL disclaimer) and I usually don't comment in HN medical threads as weird opinions here, but reading HN taking a break from my work, I'll say generally unless you have some reason like a recent dental procedure to have gotten it depending on your age I'd ask to get a (non urgent) colonoscopy or at least MR enterography or at least consideration of it with a reason why not with someone who knows the particulars of your case and can give you real medical advice.

CT has limited ability to pick up GI malignancy that can lead to translocation of bacteria from colon. If you had something like an autoimmune colitis that lead to translocation you would need to get treated and not all have preceding symptoms.

Spooky23• 1 year ago

Thank you for saying this! A loved down was “in the clear” for some stuff. Unfortunately not so clear.

Herodotus38• 1 year ago

I am also not your internist but wanted to upvote and second this comment. Op mentions being 29 years old, but should have a gi tract evaluation. Not necessarily now when dealing with the bacteremia but should be discussed.

myrloc2• 1 year ago

Great ideas, I will ask about these in the follow-up with infection disease.

Aurornis• 1 year ago

but it's not clear (and probably never will be) how it made it into my bloodstream.

The term for this is “bacterial translocation”. The intestinal barrier isn’t perfect and some level of bacterial translocation from the GI tract to the bloodstream isn’t abnormal by itself. However, some combination of increased intestinal permeability, reduced immune defense, overgrowth of the bacteria in the GI tract, or mutations of the bacteria can lead to systemic infection.

They probably gave you the “inflammation” explanation because it’s more satisfying than “it happens some times and the potential causes are diverse”.

Glad you’re doing better.

Mistletoe• 1 year ago

The more worrying thing should probably be that prozac may increase your IL-10 levels all the time. The average person doesn't encounter sepsis that often in the modern world. You don't necessarily want IL-10 boosted all the time.

https://www.sciencedirect.com/science/article/abs/pii/S13596...

"The role of interleukin-10 in autoimmune disease: systemic lupus erythematosus (SLE) and multiple sclerosis (MS)"

But the study is a single study in mice, etc. maybe the effect isn't even real.

ekianjo• 1 year ago

for those who don't know, Fluoxetine is the generic name of Prozac.

dimal• 1 year ago

Interesting, if this is holds up. I’m not smart enough to understand the mechanism. But it makes me wonder, what’s the point of designing drugs? SSRIs were developed on the faulty theory that depression was caused by low serotonin and that increasing serotonin in the brain would cure depression. It didn’t. In some percentage of people it attenuates it at varying levels, but even when it does work, it’s not by increasing serotonin levels in the brain. It’s clear that there’s some other mechanism at work.

It seems like many “wonder drug” discoveries turn out like this. A drug is created for disorder A. A lot of people take it. People start noticing other unexpected effects for disorders B-Z.

So why bother designing drugs? We already have a huge cache of approved drugs where the safety profile is known. We could look at drugs with good safety profiles and see what else they might be good for just by luck.

AStonesThrow5• 1 year ago

yay

I'm coming to suspect that the stuff used to formulate sodas, and other things regulated as foods, are nearly indistinguishable from Schedule IV/V and for all intensive porpoises, they comprise a Schedule VI of "let them eat cakes and drink ale".

Eventually there will be a Red Bull Prozac Edition and Caffeine will be smuggled over international borders: Mark My Words!!

petercooper2• 1 year ago

Not to do with sepsis, but in case it interests anyone, I read some papers a few years ago about how very low doses of fluoxetine (below the dose where it works as an SSRI, with all the side effects that confers) can stimulate the production of neurosteroids which in turn can reduce neuroinflammation, reduce anxiety, and various other things (Google "low dose fluoxetine neurosteroids" to find several).

I had chronic low-level anxiety for a few years so decided to try it and after a couple of months I realized it had all gone away. I take 5mg 2/3 times a week (clinical dose for depression is 20mg/day and up) and have had no negative side effects. My doctor knows and while they're not up on the mechanics of it, they said if it's working, keep going.

sokka_h2otribe• 1 year ago

I'm very happy this is helpful for you!

Did you know that low doses of SSRIs are regularly prescribed for general anxiety? 1/4th of a depression dose or so usually.

Sounds like you're responding well to a pretty low dose! With the halflife being what it is, taking every couple days should be similar to taking even less, but daily

I haven't read up on your suggested google terms, do you see this as different than the typical SSRI for generalized anxiety?

petercooper2• 1 year ago

do you see this as different than the typical SSRI for generalized anxiety?

I don't have a way to compare as I've never taken an SSRI or similar medication at a standard dose. However, I've had none of the common side effects associated with standard doses, so I'm inclined to believe the literature.

I'm taking roughly 1/10th the typical dose (if you average it out over time) and while it wasn't quick or "obvious", I'm happy with the outcome even if it's placebo since there are no downsides so far.

medimikka2• 1 year ago

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• 1 year 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.

rjurney5• 1 year ago

His comment isn't a medical opinion. It's a sarcastic anecdote.

rjurney5• 1 year 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• 1 year 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.

forgetfreeman• 1 year 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.

spoonfeeder0062• 1 year ago

They never said not to use Fk for major depression or other life threatening psych issues

mystified5016• 1 year ago

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.

Lerc• 1 year 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• 1 year 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.

spoonfeeder0062• 1 year 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• 1 year 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.

AStonesThrow5• 1 year ago

https://lyrics.lyricfind.com/lyrics/weird-al-yankovic-i-want...

a-dub• 1 year 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.

AStonesThrow5• 1 year 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.

anjel• 1 year ago

It takes 3-6 weeks to exert its effect on mood, so how long does it take to act upon IL-10?

AnthonBerg• 1 year ago

Haphazard guess: 2-3 days, and based on 5-HT2A receptor activation and/or Sigma-1 receptor activation rather than serotonin reuptake inhibition.

willy_k• 1 year ago

My question is why is time and money being spend on researching this, as opposed to something like its long term effects on the brain or what happens when it’s use stopped. Sure this finding is a fun thing that might be lumped into a psychiatrist’s spiel, but is there any utility for this research?

I certainly hope that someone at risk for sepsis wouldn’t be prescribed an antidepressant to treat it, or that someone already on it wouldn’t be prescribed an antibiotic anyway. Even as an adjunct for sepsis I would be highly skeptical of its practicality. Perhaps the research may provide insights into mechanisms that future drugs may be designed to exploit, but even that seems like a stretch as a justification.

wk_end• 1 year ago

as opposed to something like its long term effects on the brain or what happens when it’s use stopped.

There is no "as opposed". The people studying that sort of thing - and people do study that sort of thing - aren't the same people who are studying sepsis.

Perhaps the research may provide insights into mechanisms that future drugs may be designed to exploit, but even that seems like a stretch as a justification.

Why does that seem like a stretch? A better understanding of how the body works and/or responds to/metabolizes various drugs can absolutely guide drug discovery.

volkl48• 1 year ago

Sepsis is one of the leading causes of death and causes ~20% of all global deaths.

Research into quite literally anything that might give additional help to treating it is so obviously one of the most beneficial things we could be doing in terms of medical research that reading your post sounds completely foreign to me.

-------

Many cases of sepsis are relatively predictable in that they already know that this person is at high risk of it due to their condition or the type of intervention that's going to be required for their condition.

We're just not that great at stopping it from occurring with the tools currently available - antibiotics are not sufficient to solve/prevent it like you seem to think they are, or there'd be a lot less people dying of it.

-----

Presumably, if this research panned out in many additional trials, it's something that might be added to treatment protocols.

Even if it turned out to be useful but had limitations like being needed to be administered days in advance - there would still be significant utility for a lot of medically necessary but not immediate high-risk surgeries.

AStonesThrow5• 1 year ago

Prozac's patents expired about 23 years ago, and therefore the market pressure from generic manufacture, as well as more stylish Kardashian/Hiltonesque designs such as Sertraline, Pristique, Paxil, and Femoxitene, necessitates a neverending quest for additional ways to stand out during successive seasons of leisurely luncheons with psychiatrists, and compete for shrinking shelf/Dumpster space, as was accurately depocted in the recent documentary "Love & Other Drugs"

There's an expansion of applications, and There's a Wideness in God's pharMacy yet to be exploited, and let's face it, consumers and prescribers alike may have a gut reaction to rumors that the etiology of depression isn't necessarily a neurotransmitter deficiency.

The study long-term effects, neglect, and abuse of fluidetine is indeed already underway. However we've made a rookie mistake of forgetting that this heavy lifting is done by the attorneys and courts of civil law, where class-action suits litigate with billions at stake if they can produce enough obese 14-year-old boys who now wear underwire brassieres that harsh everyone's mellow. Long-term-effect study is a money loser and a reputation liller. No sane pill factory dares to venture into probing whatever a drug does once it's passed the cash registers and Visa terminals. Heaven forefend.

hanklazard• 1 year ago

I am absolutely floored by the depth of this paper. They really explored so much of the phenomenon and were able to dissect much of the mechanism.

This is also such a fascinating example of the body's inflammatory response to a pathogen being one of the major drivers of mortality. I suspect we'll find this to be the case in many more disease processes in the future.

rjurney5• 1 year ago

This is beautiful. So many boomers have severe chronic pain and depression... get them on Prozac and address these issues while protecting them from Covid-19 related complications.

buildsjets• 1 year ago

It's too bad that the position of the United States Secretary of Health and Human Services is that only drug addicts use Fluoxetine and that it should be banned.

shadowgovt4• 1 year ago

Interesting!

Given this pathway, and given that "Selective serotonin reuptake inhibitors (SSRIs) are some of the most prescribed drugs in the world," we should be seeing inverse correlation between increases in prescription of fluoxetine and heart disease (outside of larger novel or growing factors causing heart disease, of course).

I wonder what the research looks like in that space...

Fluoxetine promotes metabolic defenses to protect from sepsis-induced lethality

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