Invest in ME Conference 12: First Class in Every Way
OverTheHills wraps up our series of articles on this year's 12th Invest in ME International Conference (IIMEC12) in London with some reflections on her experience as a patient attending the conference for the first time.
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The Strange Cases of ME Remissions Induced by SSRIs (Dr James / Dr Smith / Dr Le Fanu)

Discussion in 'Alternative Therapies' started by Jesse2233, Jul 26, 2017.

  1. Jesse2233

    Jesse2233 Senior Member

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    I've come across something very strange and confusing. Two UK doctors in the 90s and early 2000s used SSRIs (Zoloft / Prozac) to bring a number of ME patients into remission. A third, Dr Le Fanu, conducted an informal trial with promising results. As far as I can tell Dr Smith and Dr James had a biological view of the disease with well defined patients.

    Given how many people take SSRIs, and how poorly many ME patients react to it, I'm a bit confused.

    From a document on Dr Smith's protocol.

    From the same document. Dr Le Fanu, inspired by the SSRI results invited ME patients to try sertraline via his newspaper column.

    Finally from a testimonial of a mother and daughter posted by @Jenny a while back:

     
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  2. A.B.

    A.B. Senior Member

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    This doesn't pass the common sense test.

    These medications are so widely prescribed and probably most patients have tried them. If they worked so well, we would know about it.

    There also was a trial of fluoxetine (Prozac) which was clearly negative.
     
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  3. Wonko

    Wonko Senior Member

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    The other side.
    Nearly 20 years ago, when my GP was still under the impression I was suffering from depression, I was put on Fluoxetine (Prozac). I have no idea what the dosage was but I'd assume whatever it was standard for NHS GPs to prescribe as a starting dose. This was after I had been tried on several other SSRIs with bad results.

    The results were fairly spectacular, I wasn't back to "normal" but in most aspects I was functional, I could walk, a little slower than most, but for several miles if i chose. i didn't feel ill, my head was clearer, it took a lot more to overload me e.g. I could walk through a busy town centre (but still not a shopping centre/mall type place) without significant issues etc.

    The only problem was, when the tablet began to wear off the withdrawal was bad, for several hours a day, until it was time to take the next tablet, I was in a grey hell, everything hurt, light, noise, my skin, my joints, everything -- the only fix was to take another tablet, and the after 90 minutes or so I was okay again.

    The time the tablets worked for gradually decreased over the next few months, to a few hours, with the rest of the time being spent in the grey hell, at some point during this time I decided it simply wasn't worth it, so decided to discontinue, pretty sure that was immediately before I became bedbound for several months.

    The above post makes me wonder...should I have asked for an increased dose, or did I do the right thing? in the last 20 years I've never approached being as functional as I was then, but the side effects/withdrawal......so bad I can't have been doing anything good to myself by taking fluoxetine if it did that when it ran out.
     
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  4. Jesse2233

    Jesse2233 Senior Member

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    Yes I agree which makes it so confusing. Some possible explanations.
    • Long term use, starting at very low doseages for the sudden onset cohort Dr James describes is not often tried
    • The patients were misdiagnosed and had major depression (which is unlikely given their symptoms and slow improvement).
    • The patients spontaneously improved and attributed it to the SSRIs
    • The doctors overestimated their own success rate or saw what they wanted to
    There is a possible SSRI mechanism of action that involves boosting serotonin and reducing IL-1b and TNF-a, but it's hazy.

    What struck me as interesting was that Cynthia Floud had demonstrated low blood flow to her brain stem, and the dysautonomia related to that improved with sertraline.
     
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  5. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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    "Dr Le Fanu suggested that readers with CFS/ME ask their doctors to prescribe sertraline, and begin to take it, starting with the smallest possible dose and slowly increasing it. Of the 27 readers who responded, ten found the medication to unpleasant to continue, a further ten felt there had been a definite improvement after taking them for a year - and seven ‘are astounded at how much better they feel’"

    I took Prozac near the beginning. I wouldn't be surprised if it contributed to my worsening, although it was not sertraline, and I was taking other things too. I took 20 mg. Details here: http://forums.phoenixrising.me/index.php?entries/health-notes-including-suicide-attempt-1995-6.2099/
     
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  6. Mrs Sowester

    Mrs Sowester Senior Member

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    Prozac was a complete disaster for me. I was ridiculously happy, but didn't sleep more than 2 hours a night, had some spectacular falls and was so spaced out that one of my dodgier friends wanted to know what I was 'on, cos it looks wicked'.
     
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  7. Webdog

    Webdog Senior Member

    My story is anecdotal and perhaps coincidental. That said...

    I experienced a partial remission on 200mg Zoloft (Sertraline) from 1992-95. My functioning was significantly improved (to perhaps 70%). Then I went into relapse and seemed to get no benefit from the Zoloft, so I was prescribed another antidepressant.

    Note that at the time, all my symptoms were attributed to depression or considered "all in my head". My most disabling symptoms were neuro, with lesser immune and PEM disability than I experience today.

    Zoloft is the only antidepressant (out of ~2 dozen) which I can correlate with a disease remission and improvement in functioning.

    Recently, I've considered giving Zoloft another try to see if it improves my functioning.

    Edit: I should note I had no response to Prozac.
    Edit2: I experienced no benefit at Zoloft doses below 200mg.
     
    Last edited: Jul 26, 2017
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  8. NelliePledge

    NelliePledge plodder

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    i was taking fluoxetine aka prozac for ten years before I got diagnosed with ME/CFS so not been of any help at all to me.......
     
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  9. slysaint

    slysaint Senior Member

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    In about the second year of illness (c2002) there was a recovery story in the AfME mag of a mother and daughter who 'recovered' using Lustral (Sertraline). I tried it, starting at a really low dose (cut the tablets up) and very gradually increased the dose but was not able to get it anywhere near a 'normal' dose as it really made me feel even more ill. No improvement in any symptoms so stopped after around 6 months.
     
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  10. Jesse2233

    Jesse2233 Senior Member

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    Interesting, so on this thread alone, we have 6 people who tried an SSRI. 3 were made worse, 1 had no change, and 2 got better for a variable period of time.

    Sounds like a microcosm of most treatments
     
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  11. SilverbladeTE

    SilverbladeTE Senior Member

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    it's just more bullshit to try and shore up the psych "it's all in the mind!" scumbags as their position crumbles and they are about to face the proverbial firing squad for negligence, corruption and abuse.
    they are trying to fling enough crap at the issue to delay their comeuppance, or any help for us, so I have ZERO sympathy for them

    Flouxetine and another such drug were HORRIBLE experiences for me, ugh and I believe they made me worse.
     
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  12. trishrhymes

    trishrhymes Senior Member

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    I'm sure I read something recently about SSRI drugs inhibiting enterovirus replication, so I guess it's possible it is this that helps ME sufferers, rather than the serotonin effects.
     
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  13. Webdog

    Webdog Senior Member

    That's my working theory too.
     
  14. barbc56

    barbc56 Senior Member

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    Other than a few timed when I tried changing antidepressants, I have been taking Zoloft for about twenty five years. I did not notice a change when I developed Fibromyalgia, but maybe I would have felt worse if I hadn't been taking it. I think this would be almost impossible to prove though.

    Antidepressants also reduce pain. When I unknowingly reduced my dosage my pain increased. This was after getting Fibromyalgia.

    It's very important to have an antidepressant prescrided by a competent psychiatrist.

    Monitoring is crucial as ADs can affect people in different ways. I became hypomanic on Wellbutrin. That did not mean I didn't need an AD but that it didn't work for me.

    Zoloft has been a wonder drug for me as it has controlled my depression. There's a difference between the depression of a chronic illness and clinical depression. Sometimes you can have both which makes it very difficult sorting out what is going on.
     
    Last edited: Jul 27, 2017
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  15. Forbin

    Forbin Senior Member

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    Early on, I took imipramine (tofranil) for a couple of months. All it did was raise my resting heart rate to 120+ (sometimes as high as 130). I've always figured that that could not have been good for me, even though I was in my early 20's. I stopped taking imipramine when the psychiatrist I was seeing (who seemed to suspect that my dizziness and other symptoms were psychological) essentially "fired" me after I presented him with objective test results showing an inner ear balance disorder.
     
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  16. NelliePledge

    NelliePledge plodder

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    it had helped me with depression but I wasnt depressed any more and had stopped taking it by the end of last year and not had any worsening in ME symptoms since then so literally no impact on ME
     
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  17. NelliePledge

    NelliePledge plodder

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  18. trishrhymes

    trishrhymes Senior Member

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    I've just browsed this Dr Smith's 103 page document explaining his theories and treatment protocol.

    To save others time and temper, I'll attempt to outline what I've learned from it. I skipped a lot of his ramblings about causes being stressful lives with all sorts of sweeping generalisations not based on any science.

    He was the MEA medical advisor for some years before Charles Shepherd, but fell out with the MEA when he decided that because it could be triggered by different viruses with different symptom patterns in the acute phase, including enteroviruses and Epstein Barr, but with the indistinguishable symptom patterns in the ME stage, he concluded it couldn't be caused by ongoing viral infection.

    His theory now is central (ie brain) neurological dysfunction caused by the long term life stress (I think). He seems to dismiss his own and others muscle and gut findings as irrelevant. And he rambles on for pages about stress and lifestyle and personality type and other stuff which I mostly skipped.

    He seems to have worked with Wessely and Chalder in the past, and thinks they have the same theory as he does (I think), and states that CBT and GET are successful treatments. Yet his own treatment seems to involve very strict pacing, not GET.

    Treatment

    First phase - stabilise activity at a level than can be maintained every day, with very strict restrictions on mental as well as physical activity, eg in any hour, no more than 15 minutes of visual concentration - reading, TV, computer etc., and no more than 30 minutes of audio stimulation - eg listening to the radio or an audio book. Also distance per day walked kept to planned amount that is less than what a patient says they can do. So it's strict physical and mental pacing staying rigidly within energy envelope.

    Second phase - once first phase is established an stable, get sleep pattern sorted with amitryptiline or other tricyclic antidepressant (TCA) starting with a small dose and working up to what suits the patients (usually 10 to 75 mg) taken an hour before bed. Regular bedtime, regular waking time using alarm clock. He says getting sleep sorted is a most essential part of the treatment.

    Phase 3 - SSRI, usually Prozac, morning dose starting with tiny dose and working up gradually. With the warning that SSRI and TCA aren't usually both taken because they use the same biochemical pathway in the liver for detoxification, so regular blood tests are needed to make sure it's ok. He says this is the part of the treatment that actually does the curing of the brain biochemistry, and hence leads to ME cure.

    Throughout these 3 phases keep to the strict pacing regime.

    I think he also suggested cure was less likely if you'd been ill more than a couple of years, but I'm a bit vague about that. My concentration had gone.

    The treatment can go on for several years. I don't know how he decides it's worked and is time to start taking patients slowly off the drugs (SSRI first), maybe it's when the patient feels better.

    He claims great success rates.

    My problems with this whole thing:
    He says nothing about diagnostic criteria, except vague stuff about fatigue and other symptoms, so he could be treating patients suffering from stress/burnout/depression for whom permission to slow down and take time out of their stressful lives, plus some antidepressants, is likely to be helpful.

    He says something about the Royal Free and other outbreaks, but I've forgotten, or it didn't make sense, but I got the impression he thought they were something different.

    His theories about cause and perpetuating factors are pure speculation, not evidence based.

    What he calls recovery may be patients finding a way to live at a slower pace and stay within their energy envelope, after several years of strict pacing.
     
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  19. Snow Leopard

    Snow Leopard Hibernating

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    This is why we trust randomised controlled trials, not anecdotes.

    Initial positive unblinded pilot studies (eg Behan 1994) failed to replicate in RCTs. It's a typical story of hype in medicine.

    These RCTs for a variety of SSRIs show this class of drugs are not only ineffective for CFS symptoms, but also ineffective for depression in CFS patients compared to placebo! (whereas tricyclics and monoamine oxidase inhibitors have demonstrated efficacy for depression)
     
    Last edited: Jul 27, 2017
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  20. Sidereal

    Sidereal Senior Member

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    These 1990s theories have to be understood within their historical context. Back then there was massive hype about these new drugs (SSRIs) and every problem known to man was about serotonin. Pharma was pushing SSRIs for everything and many doctors enthusiastically jumped on this wagon. Prior to SSRIs, prescribing antidepressants required psychiatric supervision so it was a relatively small market. With SSRIs now in the hands of desperate and mostly incompetent GPs who are constantly faced with various ill-defined and non-specific medical problems, it became evident that these drugs were able to cut across diagnostic categories and had some degree of effectiveness for all sorts of symptoms (probably mostly placebo in hindsight). If you read old literature you can just sort of laugh at how zealous psychiatry was about these drugs. It wasn't until around 2000, after 10+ years of indiscriminate clinical use by GPs, gynaecologists and other assorted relatively low IQ medical professionals that their true effectiveness and dangers were properly appraised and the bodies counted, so to speak.
     
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