[HN Gopher] Early clinical trial shows anti-depressant prevents ...
___________________________________________________________________
Early clinical trial shows anti-depressant prevents hospitalization
from Covid
Author : notknifescience
Score : 94 points
Date : 2021-01-09 16:04 UTC (6 hours ago)
(HTM) web link (jamanetwork.com)
(TXT) w3m dump (jamanetwork.com)
| LatteLazy wrote:
| Tiny study, just like chloroquine that is somehow still being
| talked about...
|
| >Findings In this randomized trial that included 152 adult
| outpatients with confirmed COVID-19 and symptom onset within 7
| days, clinical deterioration occurred in 0 patients treated with
| fluvoxamine vs 6 (8.3%) patients treated with placebo over 15
| days, a difference that was statistically significant.
|
| It honestly worries me how quick people are to jump on these band
| wagons. Call me when you've at least got 100 cases to review.
| NationalPark wrote:
| Is there something specific that's wrong with their math?
| LatteLazy wrote:
| They're lacking sufficient data to draw any real conclusions.
| Trend spotting like this requires very large data sets.
|
| It would be more interesting to look at (say) NHS data.
| That's the quick way to avoid this sort of guessing...
| hannob wrote:
| As unfortunate as this is, 152 isn't such a small study
| compared to what's common.
|
| Not saying this is a result that should be taken as definite,
| but it's strong enough to warrant further looking into this
| (which was never really true for hydroxychloroquine).
| LatteLazy wrote:
| You're correct, only 24 (no placebo group so I guess that's
| the equivalent of 48?). I thought it was bigger...
|
| https://www.connexionfrance.com/French-news/French-
| researche...
| hannob wrote:
| It also wasn't a randomized trial and had numerous
| methodological errors.
| lldbg wrote:
| The efficacy of the vaccines currently being administered to
| millions were based on decisions made with data from ~200
| confirmed cases.
| LatteLazy wrote:
| Pfizers stage 3 vaccine trial have 41,000 participants. I'm
| not sure how you got 200, have I misunderstood you?
|
| https://www.pfizer.com/news/press-release/press-release-
| deta....
| lldbg wrote:
| Yes, you have. The efficacy estimate was based on roughly
| ~200 confirmed cases, which your link confirms for the
| Pfizer vaccine.
| runamok wrote:
| The relevant passage is below. Basically it's a funnel,
| so It takes testing a large amount of people to tease out
| just a handful of infections. 162 cases for placebo vs. 8
| in the vaccine group.
|
| Analysis of the data indicates a vaccine efficacy rate of
| 95% (p<0.0001) in participants without prior SARS-CoV-2
| infection (first primary objective) and also in
| participants with and without prior SARS-CoV-2 infection
| (second primary objective), in each case measured from 7
| days after the second dose. The first primary objective
| analysis is based on 170 cases of COVID-19, as specified
| in the study protocol, of which 162 cases of COVID-19
| were observed in the placebo group versus 8 cases in the
| BNT162b2 group. Efficacy was consistent across age,
| gender, race and ethnicity demographics. The observed
| efficacy in adults over 65 years of age was over 94%.
| lldbg wrote:
| To be clear, I am using the example of the current
| vaccines to prove the point that N=200 allows statistical
| inferences to be drawn.
| phaemon wrote:
| The 200 you mention are comparable to the 6 in the
| comment above, not the 152.
| medntech wrote:
| The problem is the confirmed cases are the primary part
| of determining efficacy. The people who do not get the
| virus have a smaller impact on that statistic at higher
| numbers. EDIT: User runamok explains it well.
|
| [1]
| https://www.cdc.gov/chickenpox/outbreaks/downloads/appx-
| f-in...
| tinus_hn wrote:
| That would make sense because how many of these 41000
| people would have been infected without the vaccine? 200
| sounds quite reasonable.
| cosmotic wrote:
| It doesn't prevent the hospitalization, it prevents the symptoms
| that lead to hospitalization.
| ajmadesc wrote:
| From a lay perspective, That seems a bit pedantic
| DoreenMichele wrote:
| Former homemaker here: Not to me it doesn't.
| superkuh wrote:
| jamanetwork really needs to work on the accessibility of it's web
| design. Like most large online publishers of academic papers it
| recently made massive changes to it's journal sites so they're
| all javascript and CSS. Unlikely most large online publishers it
| hasn't realized what a mistake that was and implemented a
| fallback for content display in the absence of javascript
| execution. As is the page displays everything except the article
| in question (until you disable CSS).
| mrob wrote:
| I agree it's terrible web design, but like many such cases, it
| can be fixed by enabling Firefox's Reader View.
| amelius wrote:
| Several months ago there was a post about vitamin D supposedly
| being effective in preventing hospitalization. What happened to
| that idea?
| WalterSear wrote:
| It's been confirmed and supported by other studies.
| JoshTko wrote:
| Vitamin D has been shown to reduce severity in several
| different studies. Everyone should consider taking it.
|
| https://www.reddit.com/r/COVID19/search?q=vitamin+D&restrict...
|
| https://www.youtube.com/watch?v=vN30emwcNS4
| colossal wrote:
| It has shown to be _correlated_ with better outcomes. It is
| also correlated with being healthier, being active, and
| eating better. As far as I understand there is no strong
| evidence for a causal relationship.
|
| To be clear, if you live in the northern hemisphere, you
| should be taking vitamin D. It's cheap and at worst harmless.
| But that's not the same as saying it will improve the outcome
| of covid patients.
| mlyle wrote:
| IV calcifediol (Vitamin D) in early-stage COVID has
| improved outcomes in small randomized controlled trials.
|
| Oral vitamin D has been shown to be ineffective at this
| point, but this isn't surprising: it takes a long time of
| sustained oral supplementation to raise levels.
|
| Then there's a whole lot of evidence showing correlation,
| but as you point out, low vitamin D is an indicator of
| frailty. This is much weaker evidence.
|
| I think it's likely that taking oral vitamin D before
| infection probably improves outcomes somewhat.
| ekianjo wrote:
| Not just that there is a clinical trial done in spain where
| giving vitamin D as metabolized clearly improved covid19
| patient outcomes.
| metiscus wrote:
| I will say, I've been regularly taking Vitamin D for a
| while and recently started having some low back pain.
| Talked to the doctor and was told to take some magnesium.
| Apparently it is used along with Vitamin D. So if you find
| yourself in my situation, talk to your doctor.
| Izkata wrote:
| > and at worst harmless.
|
| Half true, you can take too much [0], it's just that it
| either has to build up over a long time or be from dosages
| far larger than you can buy without a prescription.
|
| [0] https://www.healthline.com/nutrition/vitamin-d-side-
| effects
| lambdaba wrote:
| Vitamin D is key to T-cell function. T-cell immunity is
| involved in mild / asymptomatic covid cases (vs antibody
| immunity).
| spion wrote:
| Its also been shown not to have an effect in at least one
| RCT, but the problem is social media skews against spreading
| that information (its kind of a downer so it won't get shared
| so much)
|
| https://www.medrxiv.org/content/10.1101/2020.11.16.20232397v.
| ..
|
| (Yes, the RCT uses cholecalciferol instead of calcifediol, so
| the reason why the intervention did not work may be that its
| a bit late. Yes, the Spanish trial had extremely good
| results,
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456194/ but it
| looked unusual (100% adherence / no dropouts). Ultimately we
| still don't know, which is appalling. We need better ways to
| conduct RCTs cheaply and efficiently!)
| amelius wrote:
| Yes, but are governments recommending it? Are doctors
| recommending it? Is WHO recommending it? I didn't hear
| anything about it except from that one post on HN, which I
| think is quite strange. If this works, then shouldn't there
| be a nation-wide plan to introduce more vitamin D in the
| diets of people?
| lambdaba wrote:
| Are you unconvinced? You know basically vitamin D is a kind
| of "master regulator" of metabolism / immune system.
|
| Deficiency of vitamin D _is_ immune system dysfunction.
| amelius wrote:
| I believe the studies, but my question is why do we let
| the health system suffer if there is such a simple
| solution? Why isn't "take vitamin D" in the same list as
| "wash your hands often" and "keep distance"?
| lambdaba wrote:
| I've seen it recommended by some authorities, but very
| timidly.
|
| There's no single answer. Vitamin D is basically a
| panacea, but for some reason most medical professionals
| don't know. Modern western medicine is on the whole
| ignorant of the role of vitamin deficiencies in disease.
| JoshTko wrote:
| Doctors (and basically any degreed professional) aren't
| interested in recommending anything that doesn't involve
| them.
| amelius wrote:
| The pandemic concerns the work and lives of just about
| any doctor at the moment.
| wolco5 wrote:
| Doctors want things to get better as much as anyone. The
| timelag between new science and what a doctor recommends
| can take a generation.
| mrfusion wrote:
| Are you sure the government cares about your health?
| amelius wrote:
| I'm sure they at least care about getting the economy
| back on track.
| JoshTko wrote:
| It was part of the regimen that Trump took when he got
| Covid.
| retrac wrote:
| For what it's worth, many government authorities already
| recommend vitamin D supplementation under varying criteria
| simply for general health. Because a lot of people in
| temperate-latitude countries really do have a mild to
| moderate deficiency:
|
| > Just over two-thirds of Canadians (68%) had blood
| concentrations of vitamin D over 50 nmol/L -- a level that
| is sufficient for healthy bones for most people. About 32%
| of Canadians were below the cut-off. About 10% of Canadians
| were below the cut-off of 30 nmol/L -- a level that is
| considered a deficiency.
|
| In Canada, everyone is advised to discuss it with their
| doctors in relation to the winter season. My doctor tests
| it with my routine blood work. Many people take a
| supplement over the winter, especially those with darker
| skin. And people over 50 have a blanket recommendation to
| take a 400 IU dose daily year-round.
| [deleted]
| cinntaile wrote:
| The NHS recommends it for example.
|
| https://www.nhs.uk/conditions/vitamins-and-
| minerals/vitamin-...
| https://www.nhs.uk/conditions/coronavirus-covid-19/people-
| at...
| amelius wrote:
| The UK's health services are struggling at the moment.
|
| So can the conclusion be that vitamin D does not work as
| expected? Or is the conclusion that still not enough
| people are taking vitamin D, and its usefulness should be
| better communicated?
| spion wrote:
| The amount recommended is insufficient for most people to
| get to the level where (correlation) has shown
| significantly reduced risk - that is >30 ng/ml (>75
| nmol/l)
|
| Another thing that is tricky is that it really depends
| how much you need to take on what your levels are
| personally. We know that the amounts they recommend are
| completely long term safe for everyone and long term good
| enough to avoid severe deficiency. But for most people
| there will still be insuficiency - the necessary average
| is actually around 2000 IU (for some people it should be
| up to 4000 IU, others less)
| wolco5 wrote:
| The reasons for UK health services failing have little or
| no connection to vitamin D.
|
| Vitamin D has shown signs that it slows down / makes
| covid less deadly.
|
| Because we don't understand: who is taking it, in what
| amounts, local weather, what the numbers would be without
| it we can't assume anything from them struggling.
| [deleted]
| ekianjo wrote:
| Relevant https://www.youtube.com/watch?v=ha2mLz-Xdpg
| lambdaba wrote:
| Yes, dosage should be 10k IU / day for starters with 5mg
| vitamin K2. Fat-soluble so take with a meal.
|
| Vitamin D depletes Vitamin A and magnesium, get the former from
| foods and supplement the latter as magnesium glycinate and/or
| chloride.
|
| Other common & relevant deficiencies are boron and zinc,
| especially zinc.
| mrob wrote:
| 10k IU/day exceeds the Tolerable Upper Intake as determined
| by the US's National Academy of Medicine, the European Food
| Safety Authority, and similar organizations. Medical doctor
| Deva Boone posted a report of toxicity at half that dose:
|
| https://www.devaboone.com/post/vitamin-d-part-2-shannon-s-
| st...
|
| This post and related posts about vitamin D were discussed on
| HN. See:
|
| https://news.ycombinator.com/from?site=devaboone.com
| lambdaba wrote:
| I know, but that's in error:
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541280/#:~:te
| x....
|
| Doctors correcting vitamin D levels are finding 10k IU is a
| good starter dose and that is often insufficient to arrive
| at optimal levels.
| nradov wrote:
| Really the only way to know the correct dose for any
| individual is to conduct occasional blood tests and
| dynamically adjust up or down. There as so many factors
| including diet, body composition, sunlight exposure,
| genetics, etc. One individual might need a daily dose
| several times higher than another.
| mrob wrote:
| Here's another report of toxicity at a similar dose:
|
| https://jeffchen.dev/posts/Vitamin-D-And-Heart-
| Palpitations/
|
| Dr Boone posted on HN, and claimed that vitamin K2 would
| not counteract high dose vitamin D:
|
| https://news.ycombinator.com/item?id=24262492
|
| I am not aware of any randomized controlled trial of
| vitamin K2 for protection against vitamin D toxicity.
| lambdaba wrote:
| In your article the person was taking this dose for 5
| years, and probably without vitamin k2 and developed
| hypercalcemia.
| DoreenMichele wrote:
| Vitamin D is still being discussed quite a lot on HN. My
| understanding is that it boils down to "It helps those who are
| deficient but doesn't do much, if anything, if you aren't
| deficient."
|
| Now, a _lot_ of people are deficient -- probably more now than
| usual due to the lock down because people aren 't getting out
| much, so people are getting less sun exposure. So I tend to get
| downvoted when I say things like "If you are deficient, you
| should redress that. If you are not, extra Vitamin D seems to
| do nothing and is potentially bad for you (because it is fat
| soluble and you can hit toxic levels in your system if you
| overconsume)."
|
| I think there may somewhat less excitement about it because it
| helps _if you are deficient_ but not if you are not, so it
| fails to serve as a drug substitute. People tend to not get
| excited about the idea that treating nutritional deficiencies
| helps shore up your body 's ability to fight disease, even in
| cases where that deficiency is fairly widespread and the
| disease in question is fairly deadly.
|
| Hoomans: Not the most logical species.
| beerandt wrote:
| Is it not any different than suggesting obese people get in
| shape to reduce their risk?
|
| Low-hanging, non-risky fruit first.
| DoreenMichele wrote:
| Lots of people who are obese have tried like hell to "get
| in shape" and failed. It's not actually a slam dunk solved
| problem to say "Just lose the weight."
|
| It pretty much is a slam dunk solved problem to say "If you
| are deficient in X, redress that." We know how to redress a
| vitamin D deficiency pretty confidently, simply and in a
| straight forward fashion.
|
| I lost several dress sizes without trying by redressing
| other things, primarily nutrient deficiencies. I focused on
| eating an aggressively nutritious diet to redress a long
| list of deficiencies rooted in a genetic disorder that
| causes gut dysfunction.
|
| So my experience fits with the general idea that "Solving
| obesity is harder than it looks and the solution may be
| something non obvious in any given case." Maybe our mental
| models of what is going on there will evolve and what I am
| saying will be "the obvious answer" to future generations,
| but it's not what is currently believed to be what works to
| solve obesity.
|
| The current mantra is "Calories in. Calories out." and
| leads to metrics like "Eat less and exercise more" and some
| people find that wholly unworkable or unsustainable for
| various reasons.
| beerandt wrote:
| Sorry, didn't mean to imply it's easy to lose weight,
| although I see that I did. Just meant that things to be
| encouraged (to reduce ones covid risk) don't necessarily
| need to be drugs that are proven to treat the disease.
|
| Including taking your vitamins, even if you don't
| normally.
| DoreenMichele wrote:
| Yes, I agree, people should be doing the "easy, obvious,
| low risk" stuff first (if they can -- lots of people
| don't have the money, can't exercise adequately because
| of lock down, etc).
|
| One of the problems is that is an inherently hard sell.
| People are terrible at measuring the disasters that
| _should_ have happened but didn 't.
|
| If you convinced everyone to take their Vitamin D
| supplements, you would have an extremely hard time
| measuring the deaths that didn't happen but should have
| and an even harder time convincing the general public you
| weren't making up BS as click bait.
|
| This is the bane of my existence. I have a serious
| medical condition and I know what _the path not taken_ is
| supposed to look like and I 've been getting better for
| nearly two decades when the condition is supposed to
| involve a steady and irreversible decline and I get told
| all the time that I am full of baloney and I can't
| possibly know that what I'm doing is effective and "X
| number of years of steady forward progress is just a wild
| coincidence -- stranger things have happened" and on and
| on.
|
| Even people who believed me and took my advice have told
| me "I gave x, y and z nutritional things to my child and
| they are in the ER less but they aren't on less
| medication." by which this person meant the child's
| maintenance drugs were the same. But they implicitly
| failed to count the fewer antibiotics, steroids and other
| emergency treatment drugs as "less medication."
|
| If you normally are in the ER every couple of months and
| need antibiotics for a month afterwards, being in the ER
| less constitutes a very significant reduction in use of
| medication. So this person was seeing results and going
| "But my child still needs just as much maintenance drugs,
| so the drug use is _the same_ as before " when it
| absolutely wasn't _the same_ as before.
|
| So what you will see here is that the general public is
| much happier if you can tell them "X number of people
| were saved by a
| vaccine/antibiotic/ventilator/hospitalization" than if
| you tell them "We convinced the entire nation to take its
| vitamins and saw a dramatic reduction in incidence of
| disease."
|
| If you tell them the second thing, the entire world will
| rise up and go "You are so full of shit. That's just a
| coincidence man. We didn't even need to take our
| vitamins. It just fucking died out for no apparent reason
| and you made me waste all this money on vitamins, you
| shit head, you."
|
| So I've mostly quit trying to talk about "Things you --
| yes, you as an individual -- can do to try to cope with
| this global pandemic." because I'm tired of being
| attacked with bullshit accusations of "practicing
| medicine without a license" and other crapola of that
| ilk.
|
| I'm pretty damn sure I will survive this -- unless I
| stupidly try to be helpful, in which case an angry mob
| may decide I am somehow to blame for something. So:
| Whatever. "You fools do whatever the fuck makes sense to
| you and leave me the hell alone."
| nradov wrote:
| The trouble with that approach is that we don't really know
| the optimal vitamin D level for human health. There are clear
| symptoms of severe deficiency. But is 20 or 30 ng/ml really
| enough? Maybe we should target a level closer to 80?
|
| The issue is further complicated by the interaction with
| other micronutrients such as calcium and vitamin K. Vitamin D
| intake has to be adjusted based on those as well. So it's
| tough to make a blanket recommendation for everyone.
| DoreenMichele wrote:
| There's always some excuse.
|
| In this situation, I would say that anyone who is high risk
| and has no affirmative reason to believe Vitamin D is
| contra indicated should consider trying to take a small
| supplement and/or get some sunlight regularly.
|
| For optimal absorption, you need to take Vitamin D, Vitamin
| K and Calcium together. Some Calcium supplements include
| those two vitamins.
|
| For optimal results, do not consume calcium and iron
| together. This means if you are trying to improve your
| nutritional status via diet, do not eat high iron foods
| (like beef, broccoli) with high calcium foods (like cheese,
| milk). They interfere with each other in terms of
| absorption.
|
| If you are in a really fragile state of health, all these
| details and more (such as bioavailability) matter a helluva
| lot. If you are not in a really fragile state of health,
| you may find that you don't need to care so much all these
| pesky details.
|
| Anyone who is really interested in their own welfare can
| and should start a food and symptom journal and read, read,
| read about health stuff (and learn how to sort the wheat
| from the chaff). If you do that, you can get to a point of
| noticing symptoms of deficiency at an early stage.
|
| I do this regularly and adjust my diet accordingly.
|
| But these are not answers people want to hear. They want a
| pill, a shot, a surgery, a solution with a really big and
| obvious and immediate change so they can look at it and go
| "I did a thing and got a result." They don't want to hear
| "You need to track it over time and see how you feel in a
| week or a month to have any real idea what helps."
|
| It's also inherently hard to isolate nutritional stuff. If
| you make any change at all to your diet, you have probably
| made multiple different changes.
|
| The way to isolate it is to start with supplements, stick
| to your normal diet, make no more than one change per week
| and keep a journal so you can track it and see what
| happens.
|
| Anything that has any health benefit will have side
| effects. Antibiotics routinely cause diarrhea and that's
| one of the more common side effects of _alternative_
| remedies, yet if I tell people that many of them will use
| that as an excuse to say "Oh, it has side effects. Nope.
| That's a big fat nope for me. I'm not doing that." even
| though it's the same side effect that antibiotics have and
| they wouldn't hesitate to take those.
|
| There's a lot of ignorance and prejudice and inherent
| resistance to resolving medical things nutritionally. In
| spite of study after study after study saying "Nutrition
| and exercise mitigate every known deadly medical condition
| ever in the history of human kind" when the rubber hits the
| road, people hand wave off nutrition as not important and
| "not something that will cure cancer, you dumbass!" and
| stuff like that.
| nradov wrote:
| This site has a fairly complete index of all the studies about
| vitamin D and COVID-19. The total weight of evidence is now
| quite strong.
|
| https://vitamin-d-covid.shotwell.ca/
| PragmaticPulp wrote:
| To be clear, this isn't saying that _any_ anti-depressant is
| effective for COVID. It appears to be a unique side-effect of
| Fluvoxamine.
|
| There are several existing drugs which have been found to have
| modulatory effects on early COVID infections. The key word here
| is "early", as most of them only have a significant impact before
| the infection gets out of control.
|
| Keep in mind that Hydroxychloroquine is one of the existing drugs
| discovered to have some effect on early infections, but it
| clearly failed to have much impact on late-stage infections.
|
| The study authors were careful to exclude severe or late-stage
| infections from their trial to avoid similar failures:
|
| > Participants were community-living, nonhospitalized adults with
| confirmed severe acute respiratory syndrome coronavirus 2
| infection, with COVID-19 symptom onset within 7 days and oxygen
| saturation of 92% or greater.
| Herodotus38 wrote:
| " Keep in mind that Hydroxychloroquine is one of the existing
| drugs discovered to have some effect on early infections, but
| it clearly failed to have much impact on late-stage infections"
|
| Do you mind sharing your evidence that HCQ helps with early
| infections? Because I know many studies that showed no benefit,
| for example:
|
| https://www.nejm.org/doi/full/10.1056/nejmoa2016638
|
| That is one of many studies.
| BlueTemplar wrote:
| There's a bunch of very professional-looking websites
| claiming the effectiveness of HCQ, especially early on :
|
| https://hcqtrial.com/
|
| https://hcqmeta.com/
|
| (And now https://c19study.com/ ?)
|
| Sadly, I only have been able to find this as criticism :
|
| https://sciencebasedmedicine.org/hcqtrial-com-astroturf-
| and-...
| YetAnotherNick wrote:
| Breakthrough: Chloroquine phosphate has shown apparent
| efficacy in treatment of COVID-19 associated pneumonia in
| clinical studies: https://www.jstage.jst.go.jp/article/bst/ad
| vpub/0/advpub_202...
| Herodotus38 wrote:
| That appears (there is no date) to be a brief paper from
| February or March. I'm interested in what you think that
| paper says?
|
| Read what the title says and read the short paper. It has
| zero references to results of use in patients other than
| referring to a news release. There is link that it is being
| used in clinical trials, but no results.
|
| We know HCQ does not do anything for Covid after hundreds
| of studies. It is time to move on. Focus on other potential
| treatments.
| mrfusion wrote:
| It would probably be any SSRI though?
| WalterSear wrote:
| It's suspected to be a specific side effect, not a part of
| the reuptake inhibition.
| PragmaticPulp wrote:
| No, it's strictly Fluvoxamine as far as we know.
|
| SSRIs aren't all interchangeable, especially when it comes to
| side effects. Fluvoxamine is very different than other SSRIs
| because it has significant effects at the sigma-1 receptor.
| The only other SSRI with significant sigma-1 activity is
| Sertraline, but it has the opposite effect at sigma-1.
|
| However, it's possible that the anti-COVID properties are
| unrelated to Fluvoxamine's actions at the serotonin
| transporter or the sigma-1 receptor. We just don't know.
| mrandish wrote:
| The similarly named Fluoxetine has lesser (but still
| significant) effects at Sigma-1. Since Fluoxetine is so
| widely distributed (because it's Prozac), there is quite a
| bit of observational data that Fluoxetine is also
| correlated with reduced clinical severity. Obviously, even
| a strong correlation is not causation but it is certainly
| grounds for prioritizing investigation, especially since
| Fluoxetine/Prozac is very well-tolerated, inexpensive and
| widely available in mass quantity.
| PragmaticPulp wrote:
| Fluvoxamine has the highest sigma-1 affinity by far.
| Fluoxetine's affinity is about an order of magnitude
| lower.
|
| We don't even know if sigma-1 is responsible for the
| effects observed, but it wouldn't make sense to give
| someone Fluoxetine instead of Fluvoxamine (which is also
| widely available), especially when it would require
| overdose levels of Fluoxetine to achieve similar sigma-1
| effects.
|
| More numbers available in the full text here:
| https://pubmed.ncbi.nlm.nih.gov/24508523/
| xkcd-sucks wrote:
| Generally speaking, "SSRI" is an ideal goal which isn't
| perfectly realized; all drugs in that class bind "off-target"
| to proteins other than SERT.
|
| In this case, fluvoxamine pharmacology is pretty clean and
| there is experimental evidence only for binding to sigma-1
| receptor in addition to SERT (also to a whole bunch of CYP
| enzymes).
|
| Unfortunately the function of sigma-1 is not well understood
| but it affects calcium signalling in intracellular
| compartments where covid-19 replicates
| mrfusion wrote:
| What's the proposed mechanism of action?
| peterebailey wrote:
| From the article:
|
| A potential mechanism for immune modulation is s-1 receptor
| (S1R) agonism. The S1R is an endoplasmic reticulum chaperone
| protein with various cellular functions, including regulation
| of cytokine production through its interaction with the
| endoplasmic reticulum stress sensor inositol-requiring enzyme
| 1a (IRE). Previous studies have shown that fluvoxamine, a
| selective serotonin reuptake inhibitor (SSRI) with high
| affinity for the S1R reduced damaging aspects of the
| inflammatory response during sepsis through the S1R-IRE1
| pathway, and decreased shock in murine sepsis models.
| euthymiclabs wrote:
| Note that "antidepressant" is largely a marketing term. The drug
| in particular is fluvoxamine, a potent selective serotonin
| reuptake inhibitor (SSRI). This doesn't mean that other
| antidepressants will work (if fluvoxamine really does work in
| larger trials).
|
| Believe it or not, fluvoxamine isn't even approved by the FDA for
| depression. It probably works, but it's only labeled for OCD (htt
| ps://www.accessdata.fda.gov/drugsatfda_docs/label/2017/02...).
| Usually, we'll preserve it for more refractory cases of OCD since
| it tends to have more side effects and interactions than other
| SSRIs.
| PaulHoule wrote:
| The sample size is small but the effect is strong, stronger than
| you almost ever see for this kind of thing.
|
| (e.g. i suspect a tiny dose of antiviral or synthetic antibody
| would be effective for prophylaxis or early treatment. By the
| time somebody is seriously ill they are sick from the cytokine
| storm and possibly clearing the virus doesnt change the course of
| the disease.)
| ericsoderstrom wrote:
| With so many studies being done on covid (by basically every
| lab in the world capable of doing so), the self selection
| biases are especially strong. That is, every study that
| confirms some statistically significant effect (often with a
| small sample size) will be published, and all of the
| corresponding studies which confirm the null hypothesis are
| buried. So you get a flood of seemingly compelling early
| evidence for covid effects or treatments, most of which will
| turn out to be false
| RobinL wrote:
| Indeed. Presumably if it is effective, you could study people
| who are using Fluvoxamine for its anti-depressive properties,
| and you'd find that (other things equal, using something like
| propensity score matching), they have less serious cases of
| COVID.
| jrochkind1 wrote:
| yup.
|
| If you flip a coin 10 times, there is less than a 5% chance
| you will get 3 or fewer tails -- so if you do, that looks
| "statistically significant" that you have a weighted coin
| (which still doesn't guarantee it).
|
| But if 500 people in different places flip a coin 10 times,
| what are the chances at least one of them will get 3 or fewer
| tails? Oops. It doesn't mean your chances of having a
| weighted coin went up.
| mrandish wrote:
| This presentation from the Covid-19 Early Treatment Fund (a non-
| profit funding over a dozen trials) summarizes the data so far on
| Fluvoxamine.
| https://docs.google.com/presentation/d/1u7resy2bGA1_HIgj6Nc7...
|
| Executive Director Steve Kirsch wrote this post on the most
| promising early treatments and CETF feels Ivermectin and
| Fluvoximine are the two most promising which they are currently
| funding studies on. He's continuing to update this post almost
| daily. As of now, the data is still insufficient to be conclusive
| (which he highlights) but I appreciate they are sharing these
| kind of insights from the front lines, at least for those capable
| of understanding the nature of evolving research and the
| associated uncertainties. Of particular interest, he links to
| Washington University's large-population, remote trial of
| fluvoximine that's free and anyone can apply and participate from
| home.
|
| https://www.quora.com/What-is-the-current-treatment-for-Covi...
| chriscappuccio wrote:
| Another excellent sigma-1 agonist is good ole OTC
| dextromethorphan. Maybe take Mucus Relief to prevent a cytokine
| storm. What if it was really this easy...
|
| As it turns out, pubmed is aware of this too:
| https://pubmed.ncbi.nlm.nih.gov/33225870/
|
| For such low risk/reward ratio, why aren't more people talking
| about these OTC treatments?
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