12 ms·

Early clinical trial shows anti-depressant prevents hospitalization from Covid

PaulHoule 6y ago
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 6y ago
  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
  - jrochkind1 6y ago
    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.
  - RobinL 6y ago
    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.
    - ketamine__ 6y ago
      I believe that is exactly how it was discovered as a potential treatment for Covid-19.
superkuh 6y ago
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 6y ago
  I agree it's terrible web design, but like many such cases, it can be fixed by enabling Firefox's Reader View.
PragmaticPulp 6y ago
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.
- mrfusion 6y ago
  It would probably be any SSRI though?
  - PragmaticPulp 6y ago
    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 6y ago
      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.
mrfusion 6y ago
What’s the proposed mechanism of action?
- peterebailey 6y ago
  From the article: A potential mechanism for immune modulation is σ-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 1α (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.
amelius 6y ago
Several months ago there was a post about vitamin D supposedly being effective in preventing hospitalization. What happened to that idea?
- WalterSear 6y ago
  It's been confirmed and supported by other studies.
- JoshTko 6y ago
  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_sr=on https://www.reddit.com/r/COVID19/search?q=vitamin+D&restrict... https://www.youtube.com/watch?v=vN30emwcNS4 https://www.youtube.com/watch?v=vN30emwcNS4
  - amelius 6y ago
    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?
    - deleted 6y ago
      [deleted]
    - lambdaba 6y ago
      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 6y ago
        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"?
LatteLazy 6y ago
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.
- lldbg 6y ago
  The efficacy of the vaccines currently being administered to millions were based on decisions made with data from ~200 confirmed cases.
  - LatteLazy 6y ago
    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-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine#:~:text=The%20Phase%203%20clinical%20trial,as%20of%20November%2013%2C%202020 https://www.pfizer.com/news/press-release/press-release-deta....
    - lldbg 6y ago
      Yes, you have. The efficacy estimate was based on roughly ~200 confirmed cases, which your link confirms for the Pfizer vaccine.
      - medntech 6y ago
        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-inv-outbrks.pdf https://www.cdc.gov/chickenpox/outbreaks/downloads/appx-f-in...
      - 6y ago
mrandish 6y ago
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_HIgj6Nc7ahzeS7DrpOtkiK5ywhQhmpk/edit#slide=id.gaeebd14cc9_0_79 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-Covid-19/answer/Steve-Kirsch https://www.quora.com/What-is-the-current-treatment-for-Covi...
- 67868018 6y ago
  Ivermectin? The animal dewormer? Did COVID suddenly grow glutamate-gated chloride channels?
  - nikolay 6y ago
    Ivermectin has been known even before COVID-19 for having antiviral properties. And it's not an animal dewormer - it's been recognized as essential medicine for humans by the WHO and there's even a Nobel Prize for Medicine awarded for its application in eradicating parasites in humans. During the last 30 years, nearly 4 billion doses of it have been applied to humans.
cosmotic 6y ago
It doesn't prevent the hospitalization, it prevents the symptoms that lead to hospitalization.
- ajmadesc 6y ago
  From a lay perspective, That seems a bit pedantic
  - DoreenMichele 6y ago
    Former homemaker here: Not to me it doesn't.
  - cosmotic 6y ago
    The very first thing that popped into my head when I read the title was "Is there some sort of legal agreement when taking the one drug that clashes with some sort of covid related law?" It's just sloppily written title that ends up asserting something that is baseless, misleading, and untrue.
chriscappuccio 6y ago
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/ https://pubmed.ncbi.nlm.nih.gov/33225870/ For such low risk/reward ratio, why aren't more people talking about these OTC treatments?
euthymiclabs 6y ago
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 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021519s009lbl.pdf https://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.
zyxzevn 6y ago
So, the capture of Afghanistan's production can help us against covid. ;-)

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 6y ago
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
- jrochkind1 6y ago
  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.
- RobinL 6y ago
  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.
  - ketamine__ 6y ago
    I believe that is exactly how it was discovered as a potential treatment for Covid-19.

superkuh 6y ago

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 6y ago
I agree it's terrible web design, but like many such cases, it can be fixed by enabling Firefox's Reader View.

PragmaticPulp 6y ago

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.

mrfusion 6y ago
It would probably be any SSRI though?
- PragmaticPulp 6y ago
  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 6y ago
    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.

mrfusion 6y ago

What’s the proposed mechanism of action?

peterebailey 6y ago
From the article: A potential mechanism for immune modulation is σ-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 1α (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.

amelius 6y ago

Several months ago there was a post about vitamin D supposedly being effective in preventing hospitalization. What happened to that idea?

WalterSear 6y ago
It's been confirmed and supported by other studies.
JoshTko 6y ago
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_sr=on https://www.reddit.com/r/COVID19/search?q=vitamin+D&restrict... https://www.youtube.com/watch?v=vN30emwcNS4 https://www.youtube.com/watch?v=vN30emwcNS4
- amelius 6y ago
  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?
  - deleted 6y ago
    [deleted]
  - lambdaba 6y ago
    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 6y ago
      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"?

LatteLazy 6y ago

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.

lldbg 6y ago
The efficacy of the vaccines currently being administered to millions were based on decisions made with data from ~200 confirmed cases.
- LatteLazy 6y ago
  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-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine#:~:text=The%20Phase%203%20clinical%20trial,as%20of%20November%2013%2C%202020 https://www.pfizer.com/news/press-release/press-release-deta....
  - lldbg 6y ago
    Yes, you have. The efficacy estimate was based on roughly ~200 confirmed cases, which your link confirms for the Pfizer vaccine.
    - medntech 6y ago
      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-inv-outbrks.pdf https://www.cdc.gov/chickenpox/outbreaks/downloads/appx-f-in...
    - 6y ago

mrandish 6y ago

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_HIgj6Nc7ahzeS7DrpOtkiK5ywhQhmpk/edit#slide=id.gaeebd14cc9_0_79 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-Covid-19/answer/Steve-Kirsch https://www.quora.com/What-is-the-current-treatment-for-Covi...

67868018 6y ago
Ivermectin? The animal dewormer? Did COVID suddenly grow glutamate-gated chloride channels?
- nikolay 6y ago
  Ivermectin has been known even before COVID-19 for having antiviral properties. And it's not an animal dewormer - it's been recognized as essential medicine for humans by the WHO and there's even a Nobel Prize for Medicine awarded for its application in eradicating parasites in humans. During the last 30 years, nearly 4 billion doses of it have been applied to humans.

cosmotic 6y ago

It doesn't prevent the hospitalization, it prevents the symptoms that lead to hospitalization.

ajmadesc 6y ago
From a lay perspective, That seems a bit pedantic
- DoreenMichele 6y ago
  Former homemaker here: Not to me it doesn't.
- cosmotic 6y ago
  The very first thing that popped into my head when I read the title was "Is there some sort of legal agreement when taking the one drug that clashes with some sort of covid related law?" It's just sloppily written title that ends up asserting something that is baseless, misleading, and untrue.

chriscappuccio 6y ago

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/ https://pubmed.ncbi.nlm.nih.gov/33225870/ For such low risk/reward ratio, why aren't more people talking about these OTC treatments?

euthymiclabs 6y ago

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 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021519s009lbl.pdf https://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.

zyxzevn 6y ago

So, the capture of Afghanistan's production can help us against covid. ;-)