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.
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.
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.
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.
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.
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.
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
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.
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.
> 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.
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.
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.
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!
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.
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.
For sure. I hope it shows nothing and it is a one off but would not want to miss something that needs treatment or predisposes you to recurrence. Take care!
> 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”.
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.
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?
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.
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.
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?
1) 7 days is a long time.
2) I believe you are confusing the common progressive dosage regimens with delayed effects. The reason fluoxetine typically takes time before you feel effects is because you take a small daily dose that build up in your system over time. It builds up since dosing is more frequent than the drugs half life.
3) Acute intake is associated with side effects, not just acute withdrawal.
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."
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.
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.
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.
> 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.
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.
> 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.
> 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.
If you meant "We should research whether mood disorders have their roots in the immune system," you should have said that instead of the absurd thing you actually said.
> 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.
Uh, no, it doesn't mean that.
In fact in extreme cases, you're dangerously wrong. Someone who is on the verge of committing suicide should not see a immunologist first, because an immunologist as they are commonly educated today is not equipped to deal with a patient on the verge of suicide. Maybe immunotherapy will be a part of the long-term solution for that patient, but they'll never make it to that point if they kill themselves first.
You are giving quack medical advice. Stop.
> 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.
Sorry, the words "I'm a huge believer" which you actually said actually do mean that you have already come to a conclusion no matter what future science might say. If you didn't mean to say that, fine, but that is actually what the words you said mean.
> For eff sake, I was just excited and not I had to waste my time explaining this to you and you ruined everything.
I didn't ruin anything. You said something completely, 100% false, and being excited is not an excuse for that.
> 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?
If you had said something as vague as "the immune system effects mental illness" I would not had any objection.
That is not what you said.
> 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?
Acute emotions caused by a short-term infection are not a mood disorder.
The incorrect claim you made which I disagreed with was about mood disorders.
> If you do not get excited, what kind of scientists are you? The most boring and uncreative kind I would say.
I am excited about new research and the potential therapies it will likely result in.
What I'm not excited about is your pseudo-scientific stream of consciousness. What you said, wasn't true, it wasn't science, and it wasn't exciting. What you said was a sloppily-worded over-confident claim that is plainly not true, and only vaguely resembles a claim that might be proven true in the future.
I am starting with your last sentence first, because it explains so much:
> What you said was a sloppily-worded over-confident claim that is plainly not true, and only vaguely resembles a claim that might be proven true in the future.
You are saying already, that my untested hypothesis is not true. Yet you say it my be proven true in the future? I never said was as true, I said it was my belief that it was true. But here you are saying it is defiantly not true.
You know, that view is well outside of the mainstream and has zero scientific evidence. If I went to my PDoc she could not prescribe me food.
> If you meant "We should research whether mood disorders have their roots in the immune system," you should have said that instead of the absurd thing you actually said.
FFS, I am not writing a thesis, I am commenting on HN.
> Someone who is on the verge of committing suicide should not see a immunologist first
Weird. I never said that. Being someone who attempted suicide twice myself I do not think that is a good idea.
> You are giving quack medical advice. Stop.
Where did I do that? Are immunologist quack doctors? Like the one I see? Hmm...
And what is it with the "Stop."? That is odd. Really controlling and you are acting like you are the Daddy to the world.
> Sorry, the words "I'm a huge believer" which you actually said actually do mean that you have already come to a conclusion no matter what future science might say.
You can hold a belief, and go in a certain direction, and when that belief is proved wrong, change your belief. Again, you are making strange assumptions. For example, I could hold the belief that turning left is the way to get to my house, act on that belief, and when I do not see my house say; "Oh I was wrong".
> If you had said something as vague as "the immune system effects mental illness" I would not had any objection.
Seems like you have difficulty with interpreting what people say based on your own strict guidelines.
> Acute emotions caused by a short-term infection are not a mood disorder.
No, but what if someone has a virus, like EBV, for a long time? Suddenly the short term mood issues is now a mood disorder.
Really, your lack of creative thought is really surprising to me.
> What you said, wasn't true,
Not yet. It is just a hypothesis that does not get tested because of the lack of funding and creative thinking in the field. You know, my mother was diagnosed with Bipolar Disorder 60 years ago and they are still trying to treat it the same exact way,
> it wasn't science
Yes, you just freaked out over my word choice. I talk to researchers everyday and I also discovered my illness was caused by a partial PNP deficiency (primary immunodeficiency) that went diagnosed my whole life. But who am I to have a "belief"?
> and it wasn't exciting.
Who are you, Spock? If you cannot get excited by science and the possibility of curing mental illness then you are lacking in the creative thought needed to move science in a beneficial direction.
> > What you said was a sloppily-worded over-confident claim that is plainly not true, and only vaguely resembles a claim that might be proven true in the future.
> You are saying already, that my untested hypothesis is not true. Yet you say it my be proven true in the future?
Your reading is as sloppy as your writing apparently. Read the bit you quoted: it does not say what you're saying it does.
> You know, that view is well outside of the mainstream and has zero scientific evidence. If I went to my PDoc she could not prescribe me food.
I have made exactly no claims about the validity of that paper. All I did was put it on my website. And I have to say, it's a bit creepy that you went and started researching me to try to win an argument. You gonna start trying to figure out where I live next?
I think that paper is interesting, and I hope it gets researched more, but I definitely do not think it should be mainstream medicine without further research. I never made that claim--that's purely your straw man hallucination. That's it. That's all I'm willing to say on this, because I'm not a doctor and I don't make up quack medical advice like you do.
> Weird. I never said that. Being someone who attempted suicide twice myself I do not think that is a good idea.
You did say that, actually. You said, "[I]f people have mood disorders they should see an immunologist first".
If you don't think it's a good idea, you should not have said it.
The rest of your post is just unhinged insults which I won't respond to--I responded to your post knowing you wouldn't like what I had to say, so it should be pretty clear that I don't care what you think of me.
> And I have to say, it's a bit creepy that you went and started researching me to try to win an argument. You gonna start trying to figure out where I live next?
David, this is weird. I went to your public website that you list in your bio to understand your world view more, because your unhinged remark about my excitement over seeing a study linking the immune system to mood disorders.
- I did not give advice to anyone. That is delusional.
- You seem to think that "people with mood disorders" and "being suicidal" has some equivalency. I think people who are suicidal need to get in a psychiatric hospital and while they are there they can see a psychiatrist and in the future, hopefully, an immunologist. Because since we do not know what causes mental illnesses we should look for every possible cause, which in some well known cases is immune related.
I get it is ok for most people to be fine with giving up on people like me and say "You have no evidence blah blah blah" while I am homeless, mentally ill, and in chronic pain. You see, somehow I keep my excitement alive during all of this, and people like you just want to kill it because "there are no studies yet" while all these people keep getting millions in grants for testing 40 year old treatments where 1/100000 of that money give to me to help me get housing would do more for my mental illness than anything else.
BTW, nutrition helped me get off all the meds that were killing me, so kudos for posting that paper on your website.
Au contraire, I am not fine on giving up on people. I wouldn't be where I am if people had given up on me.
I just want real solutions. We can say results are promising and be excited about them without being "big believers" and presenting them as more sure solutions than they are.
Nutrition has correlated with some pretty positive changes in my own mental health journey, and I think the risks of eating the foods recommended by that study are pretty low. Note how careful I am being about what I say here: speaking this carefully is what I'm encouraging you to do if you want to talk about science. All I'm asking is that you be careful that what you say is actually, specifically, true.
I'm really sorry to hear you're homeless, mentally ill, and in pain. That sucks.
Thanks. So you see, I do not have the time to be careful. Neither does anyone else like me. If I can get someone, who is currently under psychiatric care, to go see an immunologist, then that is much better.
When I tell 99% of people I meet that there is such a thing as Neuropsychiatic Lupus they are dumb founded. That has to change.
You are making it sound like I was saying people should not see psychiatrists and just see an immunologist, but that was only your interpretation. IF you asked me if I think they should see a psychiatrist as well this thread would not have happened.
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.
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.
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.
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!
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.
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.
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...
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.
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.
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.
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!!
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.
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.
> 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.
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.
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.
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