Fluvoxamine/Fluoxetine and Other FIASMA Fighters

 

The latest drugs off the shelf to show potential beneficial properties in regards to covid are fluoxetine and fluvoxamine.  Retrospective cohort studies have shown a significant risk reduction for hospitalizations and intubation or death in covid patients who are on antidepressants.  This has led to short-term use of both as yet another affordable potential therapeutic that has been here the whole time.

These two drugs in particular are known as SSRIs (Serotonin Selective Reuptake Inhibitors) Prozac and Luvox their respective brand names.  Like many drugs they have multiple effects across the body, they are also inhibitors of ASM (acid sphingomyelinase) an enzyme that cleaves sphingomyelinase into two parts resulting in a ceramide and phosphorylcholine.

During infection, the virus will activate this ASM enzyme causing excess ceramide production which results in clustering of the ACE2 enzyme on the cell membrane.  In vitro removing ceramide will stop the infection and restoring it results in the infection returning.  This makes ceramide production a ripe target for pharmacotherapy via ASM inhibition or AC (acid ceramidase) upregulation which metabolizes ceramide.

Functional inhibitors of acid sphingomyelinase (FIASMA) include many drugs across the spectrum, not just antidepressants.  Amlodipine is a calcium channel blocker that retrospective studies have also shown to reduce the covid fatality rate.  Benztropine an anticholinergic drug for Parkinson’s and Attention Deficit Hyperactivity Disorder inhibits ASM and is a Sigma 1 receptor ligand another theoretical mechanism of action that may contribute to its antiviral properties.  Clomiphene, a selective estrogen receptor modulator (SERM) blocks both covid and Ebola virus in the lab.  Hydroxyzine, a common antihistamine was shown in a study to have a significant association with reduced mortality.

Fluvoxamine though of all these has generated the most buzz due to two recently published studies.  The first, an actual randomized placebo-controlled study had eighty patients receive 100-300 mg of fluvoxamine daily for fourteen days.  Seventy-two patients received placebo and six would go on to have worsening symptoms defined as hospitalization, shortness of breath, or oxygen saturation less than 92%.  In the treatment group, zero patients would meet the criteria for worsening symptoms.

The next study looked at an even lower dose of 50mg of fluvoxamine twice daily in sixty-five patients none of which were hospitalized and at a fourteen-day follow up no patients reported any residual symptoms.  The placebo group of forty-eight volunteers resulted in six hospitalizations and twenty-nine patients reported having residual symptoms at the follow up.  Fluvoxamine like benztropine is also a Sigma 1 receptor agonist; perhaps this dual mechanism of action explains the positive results.

Jacob Hyatt Pharm D.
Father of three, Pharmacist, Realtor, Landlord, Independent Health and Medicine Reporter
https://substack.com/discover/pharmacoconuts

hyattjn@gmail.com

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Further Reading and References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488928/

Kornhuber J, Hoertel N, Gulbins E. The acid sphingomyelinase/ceramide system in COVID-19 [published online ahead of print, 2021 Oct 4]. Mol Psychiatry. 2021;1-8. doi:10.1038/s41380-021-01309-5

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570398/

Han L, Shan G, Chu B, et al. Accelerating drug repurposing for COVID-19 treatment by modeling mechanisms of action using cell image features and machine learning [published online ahead of print, 2021 Nov 5]. Cogn Neurodyn. 2021;1-9. doi:10.1007/s11571-021-09727-5

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322398/

Williams TL, Colzani MT, Macrae RGC, et al. Human embryonic stem cell-derived cardiomyocyte platform screens inhibitors of SARS-CoV-2 infection. Commun Biol. 2021;4(1):926. Published 2021 Jul 29. doi:10.1038/s42003-021-02453-y

https://www.nature.com/articles/s41421-020-00235-0

https://www.frontiersin.org/articles/10.3389/fphar.2020.582310/full

https://www.karger.com/Article/Pdf/315101

Kornhuber J, Tripal P, Reichel M, Mühle C, Rhein C, Muehlbacher M, Groemer T, W, Gulbins E: Functional Inhibitors of Acid Sphingomyelinase (FIASMAs): A Novel Pharmacological Group of Drugs with Broad Clinical Applications. Cell Physiol Biochem 2010;26:9-20. doi: 10.1159/000315101

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359627/

Hoertel N, Sánchez-Rico M, Cougoule C, et al. Repurposing antidepressants inhibiting the sphingomyelinase acid/ceramide system against COVID-19: current evidence and potential mechanisms [published online ahead of print, 2021 Aug 12]. Mol Psychiatry. 2021;1-2. doi:10.1038/s41380-021-01254-3

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786140

Hoertel N. Do the Selective Serotonin Reuptake Inhibitor Antidepressants Fluoxetine and Fluvoxamine Reduce Mortality Among Patients With COVID-19? JAMA Netw Open. 2021;4(11):e2136510. doi:10.1001/jamanetworkopen.2021.36510

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662481/

Lenze EJ, Mattar C, Zorumski CF, et al. Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial. JAMA. 2020;324(22):2292-2300. doi:10.1001/jama.2020.22760

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888564/

Seftel D, Boulware DR. Prospective Cohort of Fluvoxamine for Early Treatment of Coronavirus Disease 19. Open Forum Infect Dis. 2021 Feb 1;8(2):ofab050. doi: 10.1093/ofid/ofab050. PMID: 33623808; PMCID: PMC7888564.

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  1. kedavis Member
    kedavis
    @kedavis

    Nice to see you again, Jacob!

    • #1
  2. Mark Camp Member
    Mark Camp
    @MarkCamp

    From your article, it sounds like both of the actual studies were on infected COVID-19 patients. So the evidence is for therapeutic use, not prophylactic use.

    Did I read it correctly? (I didn’t read the papers) 

    • #2
  3. Nohaaj Coolidge
    Nohaaj
    @Nohaaj

    Mark Camp (View Comment):

    From your article, it sounds like both of the actual studies were on infected COVID-19 patients. So the evidence is for therapeutic use, not prophylactic use.

    Did I read it correctly? (I didn’t read the papers)

    Here’s the findings from one study… simple read

    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.

    • #3
  4. Nohaaj Coolidge
    Nohaaj
    @Nohaaj

    As a result of the first study, second one was conducted…

    Abstract

    We report a real-world experience using fluvoxamine for coronavirus disease 19 (COVID-19) in a prospective cohort in the setting of a mass outbreak. Overall, 65 persons opted to receive fluvoxamine (50 mg twice daily) and 48 declined. Incidence of hospitalization was 0% (0 of 65) with fluvoxamine and 12.5% (6 of 48) with observation alone. At 14 days, residual symptoms persisted in 0% (0 of 65) with fluvoxamine and 60% (29 of 48) with observation.

    • #4
  5. DonG (CAGW is a hoax) Coolidge
    DonG (CAGW is a hoax)
    @DonG

    Is there any danger of taking an SSRI for 14 days and then stopping abruptly? 

    • #5
  6. Old Bathos Moderator
    Old Bathos
    @OldBathos

    I thought FDA and CDC policy was that COVID cannot be treated with non-proprietary medications? 

    I had read a couple of the studies you cited and it occurred to me that fluoxetine and fluvoxamine appear to be getting the same results as Pfizer’s new pill.  Dr. Tony “Two Masks” F-bomb seems to see his mission as (a) propping up the nation’s worst governors and health authorities and (b) boosting big Pharma stock prices.  Can’t imagine he will not disparage fluoxetine and fluvoxamine when asked.

    • #6
  7. Misthiocracy got drunk and Member
    Misthiocracy got drunk and
    @Misthiocracy

    I was on Fluoxetine for a while.  I remember it being dirt cheap.  As such, I have zero faith it will be approved for COVID use. 

    • #7
  8. Misthiocracy got drunk and Member
    Misthiocracy got drunk and
    @Misthiocracy

    DonG (CAGW is a hoax) (View Comment):

    Is there any danger of taking an SSRI for 14 days and then stopping abruptly?

    Yes, one should be weaned off an SSRI slowly.  Stopping abruptly can be hazardous to one’s mental health.

    • #8
  9. JacobHyatt Coolidge
    JacobHyatt
    @JacobHyatt

    Mark Camp (View Comment):

    From your article, it sounds like both of the actual studies were on infected COVID-19 patients. So the evidence is for therapeutic use, not prophylactic use.

    Did I read it correctly? (I didn’t read the papers)

    yes therapeutic vs prophylactic

    • #9
  10. JacobHyatt Coolidge
    JacobHyatt
    @JacobHyatt

    DonG (CAGW is a hoax) (View Comment):

    Is there any danger of taking an SSRI for 14 days and then stopping abruptly?

    Under normal circumstances the most dangerous time for any antidepressant therapy is beginning, stopping, or dose changes.

    Since they are using a low dose for a short duration the risks from side effects would be greatly outweighed by Covid complications.  Normally though yes stopping SSRI’s cold turkey is not advised.  

    • #10
  11. JacobHyatt Coolidge
    JacobHyatt
    @JacobHyatt

    Misthiocracy got drunk and (View Comment):

    I was on Fluoxetine for a while. I remember it being dirt cheap. As such, I have zero faith it will be approved for COVID use.

    yes will never be approved no one would ever spend the money to get it approved, same principle with Ivermectin.  

    It will however be difficult to demonize fluvoxamine in the same way ivermectin was but I am sure they will give it their best effort.

    • #11
  12. Misthiocracy got drunk and Member
    Misthiocracy got drunk and
    @Misthiocracy

    JacobHyatt (View Comment):

    Misthiocracy got drunk and (View Comment):

    I was on Fluoxetine for a while. I remember it being dirt cheap. As such, I have zero faith it will be approved for COVID use.

    yes will never be approved no one would ever spend the money to get it approved, same principle with Ivermectin.

    It will however be difficult to demonize fluvoxamine in the same way ivermectin was but I am sure they will give it their best effort.

    I disagree. There’s already a substantial lobby of folk who think SSRIs are mind-control poison.  

    • #12
  13. DonG (CAGW is a hoax) Coolidge
    DonG (CAGW is a hoax)
    @DonG

    JacobHyatt (View Comment):
    It will however be difficult to demonize fluvoxamine in the same way ivermectin was but I am sure they will give it their best effort.

    It does have “flu” right in the name, so that is scary.   I heard it was used as birth control for pigs.  Maybe I made that up, but does it really matter?

    The good thing about SSRI’s is that tens of millions of Americans use every day.  I would think that if there was a prophylactic effect, it would be apparent already.  

    • #13
  14. RufusRJones Member
    RufusRJones
    @RufusRJones

    DonG (CAGW is a hoax) (View Comment):
    The good thing about SSRI’s is that tens of millions of Americans use every day.  I would think that if there was a prophylactic effect, it would be apparent already.  

    I am convinced that they don’t want to know anything about this type of thing. I just heard Dr. Atlas say that normally ivermectin would have been studied automatically and immediately because of it’s known “mechanistic action”.

    The only thing masks do is control the viral load coming out of spreaders. I would think pills would work a lot better.

    • #14
  15. Flicker Coolidge
    Flicker
    @Flicker

    JacobHyatt (View Comment):

    DonG (CAGW is a hoax) (View Comment):

    Is there any danger of taking an SSRI for 14 days and then stopping abruptly?

    Under normal circumstances the most dangerous time for any antidepressant therapy is beginning, stopping, or dose changes.

    Since they are using a low dose for a short duration the risks from side effects would be greatly outweighed by Covid complications. Normally though yes stopping SSRI’s cold turkey is not advised.

    Do you even build up a physiologically active level in just two weeks, that would cause any withdrawal?

    • #15
  16. DonG (CAGW is a hoax) Coolidge
    DonG (CAGW is a hoax)
    @DonG

    RufusRJones (View Comment):

    DonG (CAGW is a hoax) (View Comment):
    The good thing about SSRI’s is that tens of millions of Americans use every day.  I would think that if there was a prophylactic effect, it would be apparent already.  

    I am convinced that they don’t want to know anything about this type of thing. I just heard Dr. Atlas say that normally ivermectin would have been studied automatically and immediately because of it’s known “mechanistic action”.

    I think they tested ivermectin (and just about everything else) against SARS1 in vitro and it showed efficacy.   There is also the natural study of countries that have  monthly ivermectin use (to prevent River Blindness and other maladies).  As a data point, my dog has been taking ivermectin prophylactically for 2 years and has not had Wuhan Flu.

    • #16
  17. Eric Madison Member
    Eric Madison
    @EricMadison

    Thank you for this post. My sister is a nurse and has pushed the family to get the vaccine and would not consider alternative methods of treatment…until now. She was impressed by the credibility of the sourced material and the fact you took the time to reference them. 

    Thanks again!

    • #17
  18. MarciN Member
    MarciN
    @MarciN

    This is fascinating. The heart-mind-body connections are real!  :-)

    • #18
  19. OmegaPaladin Moderator
    OmegaPaladin
    @OmegaPaladin

    For reference, ceramide is a type of lipid / fat that makes up the outer layer of cells – the “membrane”.  People used to think that the membrane was a simple bag or sack for the cell, made up of lipids that were oily on one end, and water-loving on the other.  It turns out that membranes are extremely complicated, and involved in cellular signalling.  Concentrations of specific lipids in the membrane like Ceramide act as a signal flag for the cell.

    @jacobhyatt  I always appreciate your posted with their footnotes for further study.

    • #19