[HN Gopher] Fluoxetine promotes metabolic defenses to protect fr...
       ___________________________________________________________________
        
       Fluoxetine promotes metabolic defenses to protect from sepsis-
       induced lethality
        
       Author : bookofjoe
       Score  : 130 points
       Date   : 2025-02-17 13:02 UTC (9 hours ago)
        
 (HTM) web link (www.science.org)
 (TXT) w3m dump (www.science.org)
        
       | robertpohl wrote:
       | 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 wrote:
       | How would this effect gut bacteria?
        
         | meindnoch wrote:
         | Gut bacteria will be happy, because their host didn't die from
         | sepsis.
        
           | short_sells_poo wrote:
           | 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 wrote:
         | 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.
        
           | shadowgovt wrote:
           | 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 wrote:
         | 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...
        
         | shadowgovt wrote:
         | 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 wrote:
       | 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 wrote:
         | 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 wrote:
         | 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 wrote:
       | 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 wrote:
         | Now let's hear from some dead people for balance.
        
       | fny wrote:
       | 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 wrote:
         | 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 wrote:
           | Apparently 15% of cases start in hospital so that would be
           | one signal
           | 
           | https://www.verywellhealth.com/sepsis-while-
           | hospitalized-858...
        
             | Pxtl wrote:
             | There's probably a whole cocktail of meds that should be
             | administered when somebody is admitted, considering that
             | hospitals are kind of inherently dangerous and people who
             | are admitted are there because they're in a vulnerable
             | state.
             | 
             | ... well, the other thing that comes to mind like that is
             | staph infections, but I guess preemptively giving everybody
             | antibiotics to prevent that would be a good way to breed
             | superbugs.
        
         | cogman10 wrote:
         | 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?
        
           | BobbyJo wrote:
           | Fluoxetine has an insanely long half life, and your brain is
           | sensitive to its affects. Not really a viable option for
           | acute treatment.
        
             | cogman10 wrote:
             | > Fluoxetine has an insanely long half life
             | 
             | The half life is 7 days.
             | 
             | > your brain is sensitive to its affects.
             | 
             | It takes time for SSRIs to take effect. Acute usage is
             | probably ideal as you wouldn't be dealing with withdraw
             | symptoms.
        
       | yosito wrote:
       | In other words, "Study in mice suggests that taking Prozac
       | _might_ make you less vulnerable to sepsis. Further study needed.
       | "
        
       | jasongill wrote:
       | 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 wrote:
         | 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 wrote:
         | 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 wrote:
         | 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 wrote:
           | Also https://inflammatix.com/
        
         | zeagle wrote:
         | 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.
        
         | Pxtl wrote:
         | 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 wrote:
           | > _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_.
        
             | throaway89 wrote:
             | This is pretty hand-wavy. I was diagnosed with a rare
             | disorder. My doctors said surgery was the only option and
             | that it would be fine after. As it turns out, there's a
             | radiation therapy that is 80% successful, been practiced
             | around the world for 20 years with no serious side effects
             | (including cancer), AND is practiced regularly by a RO here
             | where I live.
             | 
             | I had to find out about him by myself because my doctors
             | didn't do anything other than look up my condition and give
             | me the most common treatment option. In my case surgery
             | usually makes things worse and is NOT advised other than as
             | a last resort. My doctors didn't know any of this, because
             | they didn't do their research.
        
               | cma wrote:
               | Or could be they knew the surgeon and send them business
        
         | medimikka wrote:
         | 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 >38degC (100.4degF) or <36degC
         | (96.8degF), 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 wrote:
           | What about the research surrounding high dose vit C,
           | thiamine, dexamethasone or whatever that concoction was?
        
           | jasongill wrote:
           | 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.
        
           | shadowgovt wrote:
           | 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.
        
       | FollowingTheDao wrote:
       | 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.
        
         | kerkeslager wrote:
         | > 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.
        
           | FollowingTheDao wrote:
           | 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 wrote:
       | My kid just went on this for anxierty a few weeks ago, happy to
       | hear to has some side benefits.
        
       | goda90 wrote:
       | 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.
        
         | AStonesThrow wrote:
         | have you considered dialysis and chemotherapy, or space tourism
        
       | myrloc wrote:
       | 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!
        
         | zeagle wrote:
         | 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 wrote:
           | Thank you for saying this! A loved down was "in the clear"
           | for some stuff. Unfortunately not so clear.
        
           | Herodotus38 wrote:
           | 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.
        
           | myrloc wrote:
           | Great ideas, I will ask about these in the follow-up with
           | infection disease.
        
         | Aurornis wrote:
         | > 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 wrote:
       | 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 wrote:
       | for those who don't know, Fluoxetine is the generic name of
       | Prozac.
        
       | dimal wrote:
       | 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.
        
       | AStonesThrow wrote:
       | 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!!
        
       | petercooper wrote:
       | 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.
        
       | medimikka wrote:
       | 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 a1, 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 wrote:
         | 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 wrote:
           | His comment isn't a medical opinion. It's a sarcastic
           | anecdote.
        
         | rjurney wrote:
         | 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 wrote:
           | 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 wrote:
           | 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 wrote:
             | And many other people tolerate them absolutely fine,
             | without a ridiculous number of side effects.
             | 
             | Both of us are sharing anecodtes, however.
        
           | spoonfeeder006 wrote:
           | They never said not to use Fk for major depression or other
           | life threatening psych issues
        
         | Lerc wrote:
         | 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 wrote:
         | 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.
        
       | anjel wrote:
       | It takes 3-6 weeks to exert its effect on mood, so how long does
       | it take to act upon IL-10?
        
         | AnthonBerg wrote:
         | 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 wrote:
       | 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 wrote:
         | > 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 wrote:
         | 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.
        
       | hanklazard wrote:
       | 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.
        
       | rjurney wrote:
       | 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 wrote:
       | 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.
        
       | shadowgovt wrote:
       | 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...
        
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