The Strange Cases of ME Remissions Induced by SSRIs (Dr James / Dr Smith / Dr Le Fanu)

[Hip]

As yet, we don't yet have compelling clinical trial evidence that it has potent treatment effects in paitients with chronic enterovirus infections/encephalitis/acute flacid paralysis. (I must admit I'm curious about the latter)

There is this paper, which found in a young boy with chronic enterovirus encephalitis, fluoxetine was able to improve his condition. But apart from that, I don't know of any other cases of fluoxetine being used as an antiviral for enterovirus.

I've recently been reading and learning a bit about pharmacokinetics (the study of how drugs distribute in the body tissues), and by my calculation, the concentration of free (unbound) fluoxetine in the brain tissues is over 500 times the free fluoxetine in the blood plasma (it is usually only the free drug, not the blood plasma protein-bound drug, that has active effects in the body; in the blood, fluoxetine is 95% protein-bound, which is part of the reason for its weak effects in the blood).

My calculation also showed that even low doses (eg 10 mg daily) of fluoxetine will have a potent antiviral effect in the brain.

So fluoxetine is hugely more potent as an antiviral in the brain, compared to the blood. Thus the fact that fluoxetine shows little benefit for ME/CFS suggests that perhaps enterovirus infections in the brain are not a major cause or factor in ME/CFS (but enterovirus in other tissues such as the muscles or gut might be, and fluoxetine has little antiviral effect in these tissues).

Or it might be that you don't get improvements in ME/CFS until you clear out the enterovirus infection in all of your tissues.

 

[ebethc]

I also have had my share of side effects after 3 dozen psych meds, including hallucinations, rashes covering my back, binge eating, dyskinesia, akathisia, severe insomnia and panic attacks so severe they resulted in hospitalization.

sorry to hear that.. It sounds awful. Prednisone gave me panic attacks and this overwhelming terror when I was recovering from mono... The worst time in my life, besides now, although that was way more intense...

Also, like you, I was mislabeled a depressed patient for most of my life. If not for the 2015 Institute of Medicine report, I would still be.

What did the IOM report change?

And you are correct, doctors don't warn about the side effects, nor in my experience do they take any sort of responsibility when side effects happen.

No, they don't take personal responsibility, or simply say the truth...eg, "Sorry, but the science just isn't there yet." A doctor has literally never told me that, and that's exactly what the situation is... If a doctor gave you high blood pressure meds when you don't have high blood pressure and you were injured as a result, they would have their license taken away

 

[ebethc]

But I think you and @Sidereal are probably right that this SSRI treatment of ME/CFS could be more to do with the general hype about SSRI drugs when they first came out, rather than any major benefit they have for ME/CFS.

there's still a belief that they help pain.. they're currently being re-packaged and sold as fibromyalgia drugs

Wellbutrin is being repackaged as a weight loss drug in Contrave, which also includes a lowish dose of naltrexone (8mg)

 

[Wonko]

ermm...one of the side effects I experienced from fluoxetine was trigeminal neuralgia - so not a great help at "relieving" pain in my experience.

That is, I didn't have it before taking fluoxetine, and within a few months of stopping fluoxetine it stopped, leaving only a residual sensitivity (i.e the sensation immediately before a TN attack turns to pain) that lasted for a couple of years, which totally freaked me out as TN is the most painful thing I have experienced in 51 years of "life", by a couple of orders of magnitude.

 

[ebethc]

ermm...one of the side effects I experienced from fluoxetine was trigeminal neuralgia - so not a great help at "relieving" pain in my experience.

me, neither... However, this is the POV by the infallible, all-knowing medical community and their pimps, (aka the pharma companies that give them kickbacks)... the Mayo Clinic still includes these drugs in their description of "treatment" for CFS... I have never told my family my exact dx, because they'll go on the Mayo website and see that and then insist I follow that protocol...Their incompetence has had a very big and ongoing negative impact on my life (and many others, but hopefully others at least have a support system..).

That is, I didn't have it before taking fluoxetine, and within a few months of stopping fluoxetine it stopped, leaving only a residual sensitivity (i.e the sensation immediately before a TN attack turns to pain) that lasted for a couple of years, which totally freaked me out as TN is the most painful thing I have experienced in 51 years of "life", by a couple of orders of magnitude.

Yes, I got much more sick from this chapter in my illness... it all worsened gut.. there are a lot of neurotransmitters in the gut

 

[Wonko]

As I said above it was shortly after stopping fluoxetine that I became bed bound for several months, for some reason I've never really associated it with that tho, but then until I saw your post above I'd forgotten about the TN, at times my brain does it's own thing in self defense.

TBH I can't really definitely connect the fluoxetine with being bedbound, it's just a timing thing, and for at least a year before that I'd been put on every SSRI my GP could think of, so it could have been something that was going to occur anyway, it could have been as a result of multiple SSRIs over several months, or it could have been as a result of over extending myself both from the positive effects of fluoxetine and the negative ones, including the TN. About the only thing I did learn from that experience is that SSRIs that muck around with norepinephrine have a tendence to send me bat shit crazy within a couple of days - or I think that was the conclusion I came to - it was a long time ago

 

[JES]

My calculation also showed that even low doses (eg 10 mg daily) of fluoxetine will have a potent antiviral effect in the brain.

Well explained. So having personally tested Fluoxetine at a starting dosage of 10 mg, and upping slowly towards 20 mg (an experiment which I did between September 2015 to January 2016), and getting basically no significant improvement to my chronic anxiety and CFS/ME type symptoms, it would suggest I don't have a CVB3/4 type Enteroviral infection in the brain & CFS, which was always one of my primary suspects. This will save me from doing another Fluoxetine experiment with a much higher dosage and loads of more side effects, because based on your explanation, I suspect it won't do much for other than brain type infection.

 

[Sidereal]

there's still a belief that they help pain.. they're currently being re-packaged and sold as fibromyalgia drugs

Wellbutrin is being repackaged as a weight loss drug in Contrave, which also includes a lowish dose of naltrexone (8mg)

Wellbutrin isn't an SSRI. That drug has no effect on serotonin and has a totally different side-effect profile as well.

Fibromyalgia shows some benefit from SNRIs, not SSRIs.

 

[Hip]

This will save me from doing another Fluoxetine experiment with a much higher dosage and loads of more side effects, because based on your explanation, I suspect it won't do much for other than brain type infection.

Yes, that's basically what the pharmacokinetics calculations I performed uncovered. In fact, even a 5 mg dose of fluoxetine is still enough to provide potent antiviral effects in the brain. So if anyone wanted to try fluoxetine for a suspected chronic enterovirus brain infection, you'd probably be better off using a low dose like that, which still has potent antiviral effects, but this small dose should reduce the side effects.

I am going to be posting a new thread on this subject soon: I have been spending a great deal of time recently looking at various drugs and supplements (including fluoxetine) that have potent antiviral effects against enteroviruses in vitro, and then using pharmacokinetics to try to calculate whether these compounds can achieve the same potent antiviral effects in vivo, when you actually take the drug orally.

It turns out that lot of these compounds cannot achieve the same antiviral effect in vivo, because you just can't get the same concentrations of the compound (the concentrations used in the in vitro antiviral studies) in the human body tissues (because the oral dose to do so would be far too high).

For example, in the case of fluoxetine, I calculated that the oral dose required to achieve the antiviral concentrations used in the in vitro antiviral studies would be around 2,000 mg daily ! That's well beyond the safe fluoxetine maximum daily dose of around 80 mg. So although fluoxetine is a potent antiviral in vitro, in practice, you cannot really achieve these potent antiviral effects in the body. (Although fluoxetine concentrates in the spleen and liver, so in these organs, it may have potent antivirals effects at low doses)

However, as mentioned, in the brain it is a different story, as fluoxetine concentrates in the brain, and I was able to calculate that the fluoxetine daily oral dose required to achieve potent antiviral effects in the brain was only 5 to 10 mg.

 

[Hip]

I found Dr Ian James's observation of "pupil wobble" in ME/CFS patients interesting:

He had noticed that ME patients usually had ‘pupil wobble’ after a bright light had been flashed at their eyes. The pupil closed but then failed to open to the correct size; instead it wobbled away, letting in too much light & causing the hatred of brightness with which we were all too familiar.

He used this to measure whether the drug was working before we could notice any changes. We had high tech pupillometry tests both before we took the Lustral and again after 6 weeks taking it. [We later learnt that an improvement in pupil wobble did indeed predict those who would later improve.]

Might this pupil wobble be a useful diagnostic marker for ME/CFS?

I was shining a light into my eyes to see if I could observe this pupil wobble effect, but it is not that clear from the above description what exactly you are supposed to observe.

It sounds like you should see constant variation in pupil diameter (the "wobble") under a bright light, but this is not what I see with my eyes: when I shine a torch light onto my eyes, the pupil diameter instantly reduces as you would expect, but then stays fixed at the reduced diameter while the torch light is still shining on it, without any "wobbles". Then when I remove the torch light, the pupil opens back up to its previous diameter within a few seconds.

 

[me/cfs 27931]

What did the IOM report change?

The IOM report:

• Stated clearly that ME/CFS was not a psychological disorder.
• Had diagnostic criteria that my doctor found acceptable.
• Was from an authoritative source my doctor couldn't ignore. My longterm contention that I had a physical disease with real symptoms was finally validated.

Until the IOM report came out, I was considered a treatment-resistant depression patient with fatigue/sleep issues and imaginary disease symptoms. After all, my bloodwork was fairly normal, so how could it be anything but psychological?

This report completely changed my life.

 

[Wonko]

Unfortunately my Doctor has refused to read anything ME related unless it's on treatment and approved by NICE - so absolutely nothing

 

[hinterland]

I just started a related thread, that might be of interest:

Low-dose SSRI to reduce neuronal apoptosis in the stress pathways and amygdala

Thanks.

 

[eric_gladiator]

I have seen cases where people say they improve with an antidepressant, something that I still have in doubt with myself after trying duloxetine and feeling much worse than I was. I still have fluoxetine, sertraline, clonazepam and some other medication at home. Maybe some day I will do some experiment at the risk of worsening my condition but who knows the same way.

 

[Learner1]

I have seen cases where people say they improve with an antidepressant, something that I still have in doubt with myself after trying duloxetine and feeling much worse than I was. I still have fluoxetine, sertraline, clonazepam and some other medication at home. Maybe some day I will do some experiment at the risk of worsening my condition but who knows the same way.

Most psychiatric drugs damage mitochondria, which could make you feel much worse than you were.

 

[eric_gladiator]

@Learner1
Does that mean it's not worth trying?

 

[Learner1]

If you understand the risks of anything you try, which may include permanent damage.

I point this out, not to be argumentative, but because my mitochondria were damaged from Cipro, carboplatin, and paclitaxel, drugs my doctors blithely prescribed without any warning about possible mitochondrial damage.

It was only when I went to a mitochondria conference and heard Robert Naviaux speak passionately to an audience of doctors, warning them to be wary of prescribing anything to their delicate patients as so many drugs damage mitochondria, and heard researchers who'd tested the drugs for mitochondrial toxicity that I became aware of the issue.

What problem are you trying to solve?

If you're trying modulate your immune system, there are a lot of other choices. If you're depressed or anxious, the answer could lie in vitamin, amino acid, or fatty acid deficiencies.

And psychiatrists do not seem to be understanding of ME/CFS as a multi organ system autoimmune disease and are ill equipped to do the lab work to uncover immune system issues, infections, microbiome disturbances, mold or heavy metal toxicity, or nutrient deficiencies which have all been found in ME/CFS patients, and do not typically provide a robust variety of treatments.

...or, if all you have is a hammer...

 

[ebethc]

If you understand the risks of anything you try, which may include permanent damage.

much, much worse after trying these types of drugs... single biggest mistake in my treatment... they did nothing positive, and screwed up my gut much worse than it was and caused weight gain... and I can believe the mito damage ( @Learner1 - do you have any links? i think that I've seen a table somewhere w drugs that cause mito damage, but if there's something else, I'd like to see it..).. Still considered a "standard" cfs tx.

 

[JES]

@Learner1
Does that mean it's not worth trying?

I don't know if the mito damage is really significant. Dr. Naviaux attributes mito damage to a lot of drugs, but he is pretty much the only researcher to do so. There are some drugs that provenly cause mitochondrial damage, but antidepressants generally speaking haven't been proven to do so.

I can't make a decision for you, but I can say it's probably not worth to try many drugs from the same class. Like from SSRI class, all drugs work in rather similar fashion, the main difference is in their side effects.

 

[Learner1]

much, much worse after trying these types of drugs... single biggest mistake in my treatment... they did nothing positive, and screwed up my gut much worse than it was and caused weight gain... and I can believe the mito damage ( @Learner1 - do you have any links?.

Here are a few:

https://www.ncbi.nlm.nih.gov/m/pubmed/18626887/

http://www.mitoaction.org/toxins

http://www.mitoaction.org/blog/medication-exposures-mitochondrial-toxicity

http://www.sciencedirect.com/science/article/pii/S0014579305009993

https://www.ncbi.nlm.nih.gov/m/pubmed/22387747/

https://www.ncbi.nlm.nih.gov/pubmed/20941696

https://www.ncbi.nlm.nih.gov/m/pubmed/26992920/