Fluoxetine - antiviral application

[JES]

A couple of years ago there was news about Fluoxetine (Prozac) being discovered as an enterovirus antiviral, though its effect was only analyzed in vitro [1][2]. Today I stumbled upon a new article on the application of Fluoxetine for HCV, which caught my interest, as this study was performed on humans [3].

I have CFS symptoms resembling of enteroviral infection, including myocarditis which is typically caused by Coxsackie B3 virus. So I decided to start a trial on Fluoxetine in the next couple of weeks, as I couldn't find any reports on it online for this particular application. I will be reporting on my progress here, hopefully shortly.

Antiviral Res. 2014 Oct;110:158-67. doi: 10.1016/j.antiviral.2014.08.002. Epub 2014 Aug 21.
Fluoxetine a novel anti-hepatitis C virus agent via ROS-, JNK-, and PPARβ/γ-dependent pathways.
Young KC1, Bai CH2, Su HC3, Tsai PJ1, Pu CY2, Liao CS4, Lin YM4, Lai HW4, Chong LW4, Tsai YS5, Tsao CW6.
Author information
Abstract
More than 20% of chronic hepatitis C (CHC) patients receiving interferon-alpha (IFN-α)-based anti-hepatitis C virus (HCV) therapy experienced significant depression, which was relieved by treatment with fluoxetine. However, whether and how fluoxetine affected directly the anti-HCV therapy remained unclear. Here, we demonstrated that fluoxetine inhibited HCV infection and blocked the production of reactive oxygen species (ROS) and lipid accumulation in Huh7.5 cells. Fluoxetine facilitated the IFN-α-mediated antiviral actions via activations of signal transducer and activator of transcription (STAT)-1 and c-Jun amino-terminal kinases (JNK). Alternatively, fluoxetine elevated peroxisome proliferator-activated receptor (PPAR) response element activity under HCV infection. The inhibitory effects of fluoxetine on HCV infection and lipid accumulation, but not production of ROS, were partially reversed by the PPAR-β, -γ, and JNK antagonists. Furthermore, fluoxetine intervention to the IFN-α-2b regimen facilitated to reduce HCV titer and alanine transaminase level for CHC patients. Therefore, fluoxetine intervention to the IFN-α-2b regimen improved the efficacy of anti-HCV treatment, which might be related to blockades of ROS generation and lipid accumulation and activation of host antiviral JNK/STAT-1 and PPARβ/γ signals.

Copyright © 2014 Elsevier B.V. All rights reserved.

KEYWORDS:
Fluoxetine; Hepatitis C virus; Interferon-α; JNK; PPAR-β/γ; STAT-1

 

[halcyon]

Look forward to hearing how your trial goes. I know Dr. Chia has talked about trying it in the past but I'm not sure if he's actually had any patients go on it.

Have you looked into beta interferon at all for the myocarditis?

 

[Gingergrrl]

@JES how was your myocarditis diagnosed and what symptoms do you have? Thank you for any info!

 

[JES]

@JES how was your myocarditis diagnosed and what symptoms do you have? Thank you for any info!

Sudden cardiac symptoms (palpitations, chest pain etc) after feeling more sick for a couple of days, abnormal EKG. I've had periods of this about once every second year until this year when I've had it twice already. I'm quite convinced chronic enteroviral heart infection is directly related or probably even main cause of my CFS symptoms.

@halcyon Nope, and I think it would be difficult to get any specific treatment for chronic viral infection in this country.

 

[halcyon]

@halcyon Nope, and I think it would be difficult to get any specific treatment for chronic viral infection in this country.

That's too bad. How about oxymatrine/Equilibrant?

 

[Gingergrrl]

Sudden cardiac symptoms (palpitations, chest pain etc) after feeling more sick for a couple of days, abnormal EKG. I've had periods of this about once every second year until this year when I've had it twice already. I'm quite convinced chronic enteroviral heart infection is directly related or probably even main cause of my CFS symptoms.

Hi @JES and thanks for the info re: your experience. I was curious if a cardiologist diagnosed you with myocarditis, or a virus inside your heart, using specific testing or if it was based solely on your symptoms?

It sounds like you had very acute episodes with feeling more sick plus the abnormal EKG (which I have not had) versus in my case, an ongoing chronic issue with shortness of breath and dysautonomia where we suspect that the blood does not fill my lungs & heart properly especially when I stand.

But one of my docs always goes back to the myocarditis theory whereas my cardio absolutely dismisses it and says my EKG's and echo's, etc, are normal and there is no evidence of it which often leaves me confused!

In your case, when you said you already had this infection twice this year alone, did it resolve on it's own both times or did you receive any treatment? Like an anti-viral or anything else? I apologize for all the questions and really appreciate you taking the time to respond! I hope you get some answers and feel better soon.

 

[JES]

@Gingergrrl Your symptoms with dysautonomia etc. sound more "classic" CFS than mine, so sadly I'm not surprised doctors don't take you serious. I was given diagnosis myocarditis/pericarditis based on one single piece of arrhythmia caught on EKG. In previous times when I got these sudden heart symptoms EKG never caught anything so nobody cared much about my complaining. Ironically, this single abnormal EKG now caught the doctor's interest and I'm supposed to temporarily take all kinds of heart medication and consult with cardiologist, probably doing some ultrasound of heart, even though my feeling is better now than last time.

It is what it is and I don't expect to get any treatment for the real cause, nor test for any viruses (not that such tests would help much anyways). It did resolve on it's own last time and I'm confident it will this time within weeks. I'm just not able to clear this virus completely or my immune system is dealing with too many pathogens, is my concern. At least this time I'm aware of some natural antivirals for enterovirus such as high-dose selenium and my upcoming Prozac experiment. I will also test oxymatrine at some point if I can get access to it, although I react badly to immune stimulants in general.

 

[Gingergrrl]

@Gingergrrl Your symptoms with dysautonomia etc. sound more "classic" CFS than mine, so sadly I'm not surprised doctors don't take you serious. I was given diagnosis myocarditis/pericarditis based on one single piece of arrhythmia caught on EKG. In previous times when I got these sudden heart symptoms EKG never caught anything so nobody cared much about my complaining. Ironically, this single abnormal EKG now caught the doctor's interest and I'm supposed to temporarily take all kinds of heart medication and consult with cardiologist, probably doing some ultrasound of heart, even though my feeling is better now than last time.

It is what it is and I don't expect to get any treatment for the real cause, nor test for any viruses (not that such tests would help much anyways). It did resolve on it's own last time and I'm confident it will this time within weeks. I'm just not able to clear this virus completely or my immune system is dealing with too many pathogens, is my concern. At least this time I'm aware of some natural antivirals for enterovirus such as high-dose selenium and my upcoming Prozac experiment. I will also test oxymatrine at some point if I can get access to it, although I react badly to immune stimulants in general.

@JES, thank you for taking the time to explain all that and I was curious what country you are in? I am starting to think mine are more severe dysautonomia than anything else but have docs with all differing opinions! Although I have never had anything show up on an EKG or Echo, even at my sickest. What types of meds did they recommend for the myocarditis? Thanks again!

 

[JES]

A couple of years ago there was news about Fluoxetine (Prozac) being discovered as an enterovirus antiviral, though its effect was only analyzed in vitro [1][2]. Today I stumbled upon a new article on the application of Fluoxetine for HCV, which caught my interest, as this study was performed on humans [3].

I have CFS symptoms resembling of enteroviral infection, including myocarditis which is typically caused by Coxsackie B3 virus. So I decided to start a trial on Fluoxetine in the next couple of weeks, as I couldn't find any reports on it online for this particular application. I will be reporting on my progress here, hopefully shortly.

Nearing one month of fluoxetine usage now. The first few weeks were not good; had to cut the dosage to half due to some restlessness and insomnia (I did expect this). After that the antidepressant effect slowly kicked in, but my neuroimmune symptoms got worse than ever, probably due to immunomodulatory effects of this drug. Last few days have given more promise: less brainfog, anxiety, less of all the typical symptoms I have. I have hope that this drug would treat what I suspect as chronic enteroviral infection of CNS and brain, but definite results remains to be seen in the upcoming months.

Myocarditis is recovering, slowly (probably would have done regardless of fluoxetine).

 

[halcyon]

I have hope that this drug would treat what I suspect as chronic enteroviral infection of CNS and brain, but definite results remains to be seen in the upcoming months.

Yeah it's unclear how long it might take to start seeing an effect if there will be one. A few months seems reasonable though. Keep us posted.

 

[JES]

I've now assessed the use of fluoxetine for 4 months to see if it helps my CFS symptoms, unfortunately without seeing the effect I was hoping for. The result was disappointing as the antiviral properties sound impressive on paper, especially considering fluoxetine reach the brain and CNS in high concentration.

I was only able to withstand a 10 mg dosage without getting unacceptable side effects (hypoglycaemia, fatigue, lack of focus etc.). This is half of the recommended starting dosage of 20 mg, but I suspect even 20 mg will not be enough for the anti-enteroviral effect to show up. It's also possible that I have an entirely different virus, but myocarditis and coxsackievirus often go together.

So to sum it up, I didn't experience any lasting positive effects, whereas plenty of negative side effects developed through this period. I will next do a similar experiment on buspirone which has shown immunomodulatory effects in at least one study.

 

[Gingergrrl]

Ironically, this single abnormal EKG now caught the doctor's interest

@JES Do you happen to remember what the single abnormal thing was on the EKG that triggered the doc to think of myocarditis? I had a weird thing on EKG back in May at hospital (which I didn't even learn of until recently) but then had an EKG a few weeks ago and it was totally normal.

Myocarditis is recovering, slowly (probably would have done regardless of fluoxetine).

Am glad to hear it is recovering, great news.

So to sum it up, I didn't experience any lasting positive effects, whereas plenty of negative side effects developed through this period.

Sorry to hear that but I guess it's good you experimented with it and now you know.

 

[halcyon]

It's also possible that I have an entirely different virus, but myocarditis and coxsackievirus often go together.

The effects of these various compounds seems to vary even between serotypes of enteroviruses.

So to sum it up, I didn't experience any lasting positive effects, whereas plenty of negative side effects developed through this period.

Really sorry to hear this.

I will next do a similar experiment on buspirone which has shown immunomodulatory effects in at least one study.

Be aware that the hypothalmic response to buspirone (with large production of prolactin) was used in several studies as a surrogate marker for patients with enteroviral ME. Many of them reported increased fatigue, dizziness, and nausea from buspirone. I'm guessing though that you had similar effects from the fluoxetine.

 

[adreno]

I was only able to withstand a 10 mg dosage without getting unacceptable side effects

Funny you should say this; I'm on fluoxetine as well and also do not tolerate more than 10mg.

Be careful when you stop the drug; the half life is about 1 week and should provide a sufficient taper, but I have tried reducing to 5mg on several occasions and it has always ended in disaster. Hope you do better.

 

[anciendaze]

Why is it I find discussions about pharmacodynamics on patient forums rather than doctors? Why is there strong awareness here of individual variations in sensitivity that are virtually absent in the literature? (Yes, I know there are such professional forums. I also know about groups of doctors touting the drug where it turned out none of them could even list side effects.)

 

[JES]

Thanks for the warnings, wasn't aware of this issue with buspirone. So far (3 days in) side effects have thankfully been less than from my Fluoxetine trial. Will also taper off Fluoxetine slowly to be safe.

@JES Do you happen to remember what the single abnormal thing was on the EKG that triggered the doc to think of myocarditis?

The diagnosis was never confirmed by cardiologist, I can't remember exactly but EKG showed in one small interval some type of arrhythmia (I guess I was lucky). The past times I've had this same thing EKG showed nothing and doctors pretty much ignored me. That along with my other symptoms (rapid heartbeat, some pain in chest area combined with extra sick feeling) gave the doctor the clue that I probably had suffered a mild myocarditis triggered by a cold.

What leads me to think that it's related to CFS is that I've had this same kind of myocarditis thing four times now in the past 6 years, each time triggered randomly, no heavy exercise involved or anything that usually causes it in healthy people. Plus I have some other mild heart symptoms as well related to CFS, so it's all a bit tricky.

Why is it I find discussions about pharmacodynamics on patient forums rather than doctors? Why is there strong awareness here of individual variations in sensitivity that are virtually absent in the literature? (Yes, I know there are such professional forums. I also know about groups of doctors touting the drug where it turned out none of them could even list side effects.)

In my experience this lack of understanding goes way beyond medication side effects. Among the psychiatrists I've visited, none has even bothered to investigate if I got any related physiological illness that could contribute to my symptoms. The only focus is on the behavioral aspects, talk therapy, etc. Then at the end you are offered a medication without given any explanation on how it works. The only reason for a CFS patient to visit these doctors IMO is for trialling new drugs. My approach is a bit similar to Dr. Jay Goldstein, who apparently managed to "cure" some lucky CFS patients by randomly prescribing these type of drugs.

 

[ScottTriGuy]

I am under the impression that most anti-depressants are also generally neuro-protective (including anti-inflammatory??)

 

[MadeleineKM]

This might explain why I got less of my cronic fever when I was on Fluoxetine. I could only handle 5g. Its important to be very careful and take time with increasing the dose if you are sensitive

 

[adreno]

I am under the impression that most anti-depressants are also generally neuro-protective (including anti-inflammatory??)

Yes, most (if not all) of them are.

 

[JollyRoger]

I know this this thread is old but I found something interesting yesterday.

http://www.pedneur.com/article/S0887-8994(16)30209-0/abstract

Chronic encephalitis successfully treated.

Everyone with positive entero results maybe just need some antidepressants