Fluoxetine promotes metabolic defenses to protect from sepsis-induced lethality

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.

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?

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.

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.

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.

> 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.

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.

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.

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

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.

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.

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.

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.

> 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.

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

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?

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?

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?

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...

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.

> 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.

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

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.

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...

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.

have you considered dialysis and chemotherapy, or space tourism

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

> 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.

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.

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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.

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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.

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.