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A Systematic Review of Drug Therapies for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Discussion in 'Latest ME/CFS Research' started by Kati, May 26, 2016.

  1. Kati

    Kati Patient in training

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    News from Griffith University on facebook:

    Dear Supporters,

    NCNED would like to sent a great thank you to all our sponsors, donors and participants of our research. Without your support, our research here would not be possible.

    As a result of this support, May has been a big month for us here at NCNED with another paper published. This paper reviews the existing evidence on drug therapies with an aim to determine whether any can be recommended for patients for CFS/ME. The full paper may be accessed by clicking on the link below.

    http://www.sciencedirect.com/…/article/pii/S014929181630306X

    Clinical Therapeutics
    Available online 24 May 2016, doi:10.1016/j.clinthera.2016.04.038

    In Press, Corrected Proof — Note to users

    A Systematic Review of Drug Therapies for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
    • Ansel Collatz BA (Human Bioscience), MPH
    • Samantha C. Johnston BBiomedSc, MIPH, MHEcon, PhD
    • Donald R. Staines MBBS, MPH, FAFPHM, FAFOEM
    • Sonya M. Marshall-Gradisnik BSc (Hons), PhD
    Abstract

    Purpose
    The pathogenesis of chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is complex and remains poorly understood. Evidence regarding the use of drug therapies in CFS/ME is currently limited and conflicting. The aim of this systematic review was to examine the existing evidence on the efficacy of drug therapies and determine whether any can be recommended for patients with CFS/ME.

    Methods
    MEDLINE, EMBASE, and PubMed databases were searched from the start of their records to March 2016 to identify relevant studies. Randomized controlled trials focusing solely on drug therapy to alleviate and/or eliminate chronic fatigue symptoms were included in the review. Any trials that considered graded exercise therapy, cognitive behavior therapy, adaptive pacing, or any other nonpharmaceutical treatment plans were excluded. The inclusion criteria were examined to ensure that study participants met specific CFS/ME diagnostic criteria. Study size, intervention, and end point outcome domains were summarized.

    Findings
    A total of 1039 studies were identified with the search terms; 26 studies met all the criteria and were considered suitable for review. Three different diagnostic criteria were identified: the Holmes criteria, International Consensus Criteria, and the Fukuda criteria. Primary outcomes were identified as fatigue, pain, mood, neurocognitive dysfunction and sleep quality, symptom severity, functional status, and well-being or overall health status. Twenty pharmaceutical classes were trialed. Ten medications were shown to be slightly to moderately effective in their respective study groups (P < 0.05).

    Implications
    These findings indicate that no universal pharmaceutical treatment can be recommended. The unknown etiology of CFS/ME, and complications arising from its heterogeneous nature, contributes to the lack of clear evidence for pharmaceutical interventions. However, patients report using a large number and variety of medications. This finding highlights the need for trials with clearly defined CFS/ME cohorts. Trials based on more specific criteria such as the International Consensus Criteria are recommended to identify specific subgroups of patients in whom treatments may be beneficial.
     
  2. taniaaust1

    taniaaust1

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    Sounds like a good bit of research even if it didnt come up with anything. We needed a study like this.

    Now we just need a study like this on the ones which meet the ICC.

    "Ten medications were shown to be slightly to moderately effective in their respective study groups (P < 0.05)."

    I cant get it up being FB, can anyone please tell me what those 10 were?
     
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  3. halcyon

    halcyon Senior Member

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    Hydrocortisone, rituximab, NAD, Nefazodone, Moclobemide, IVIG, ALCAR, Dextroamphetamine, Rintatolimod, and lisdexamfetamine.
     
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  4. Sasha

    Sasha Fine, thank you

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    I haven't even heard of most of that stuff. Are some of those palliative therapies for pain and sleep and OI, rather than things attempting to tackle with the underlying process?
     
  5. halcyon

    halcyon Senior Member

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    Not familiar with some of them but I don't think we can say without knowing what the underlying process is. Here's the table that shows which domains the improvements were in:

    table.png
    table2.png
     
  6. Bob

    Bob

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    These are usually small, isolated, studies of heterogeneous cohorts, so the info should be regarded with suitable scepticism.

    The 'effectiveness' column tells you what sort of effect the studies found. Based on standard effect sizes, my interpretation is that "slightly effective" means barely discernable, "mildly effective" means discernable but not useful, and "moderately effective" means it makes a bit of a difference in some patients but nothing drastic and no major changes to your life. Even in a "moderately effective" study, only a small proportion of patients might respond to the treatment.

    I don't want to kill people's hopes, but I'm just attempting to put the outcomes into perspective. It's partly why the conclusion of the study says: "These findings indicate that no universal pharmaceutical treatment can be recommended."

    Acetyl-L-carnatine and nicotinamide adenine dinucleotide (NAD) are widely available supplements and are (according to the chart) moderately effective, but the studies are small isolated studies and if these substances were particularly useful then we'd already know about it. They might be worth a try, but expectations should probably be low.

    But some people might benefit from, and respond well to, some of the listed substances.
     
    Last edited: May 26, 2016
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  7. taniaaust1

    taniaaust1

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    "Hydrocortisone, rituximab, NAD, Nefazodone, Moclobemide, IVIG, ALCAR, Dextroamphetamine, Rintatolimod, and lisdexamfetamine."

    thanks Halcyon

    for anyone wondering, I've been looking up those drugs as I havent heard of most of them either.

    "Nefazodone hydrochloride is a phenylpiperazine antidepressant with a mechanism of action that is distinct from those of other currently available drugs. "

    " For venlafaxine and nefazodone, downregulation of the postsynaptic b1 adrenoceptor and 5HT receptor appears to be important. The adverse effects of these new medications can be understood in terms of their effects on central and peripheral serotonergic and adrenergic receptors. "
    ......

    Moclobemide (sold as Amira, Aurorix, Clobemix , Depnil and Manerix) is a reversible inhibitor of monoamine oxidase A (RIMA) drug primarily used to treat depression and social anxiety. It is not approved for use in the United States, but is approved in other Western countries such as the UK and Australia.

    ...................

    Acetyl-L-carnitine, ALCAR or ALC, is an acetylated form of L-carnitine. It is naturally produced by the body, although it is often taken as a dietary supplement.
    .............

    Dextroamphetamine (American English) or dexamfetamine (Commonwealth English) [note1] is a potent central nervous system (CNS) stimulant and amphetamine enantiomer that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy.
    ....................

    Rintatolimod, sold under the tradename Ampligen, is a medication intended for treatment of chronic fatigue syndrome.

    ..............

    lisdextroamphetamine) is a central nervous system (CNS) stimulant and dextroamphetamine prodrug of the phenethylamine class and amphetamine class that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and binge eating disorder.
     
    Last edited: May 26, 2016
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  8. Graham

    Graham Senior Moment

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    I've got a vested interest in the steroids (hydrocortisone) as I have been taking a low dose prednisolone for many years. There appears to be a small subset of us who benefit from it, but a larger subset who find it gives them extra problems.
     
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  9. Valentijn

    Valentijn The Diabolic Logic

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    There might not be many people having problems with low dose hydrocortisone. The psychobabbler studies had pretty good results with it, which seemed to scare the crap out of them and cause them to recommend that it never be used outside of research. But there wasn't much indication of side effects, from what I recall.
     
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  10. JamBob

    JamBob Senior Member

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    I take low-dose Hydrocortisone. I don't think I'd still be here without it. I never had a synacthen test before taking the hydrocortisone but my serum (9am) cortisol was very low - below the range.

    I don't think the hydrocortisone is a cure for ME as I still have a lot of issues with my energy systems (whatever they are!), dysautonomia and my immune system. Before HC, I was bedridden,had major unexplained weightloss, terrible muscle weakness 24/7, marked postural hypotension and recurrent hypoglycaemia etc.

    I seem to recall that Dr Bansal had some research suggesting that patients with ME are in a kind of "functional" state of Addison's disease though I don't think he published it.
     
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  11. Sasha

    Sasha Fine, thank you

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    So is there a test that suggests that low-dose hydrocortisone would be a good idea?
     
  12. Valentijn

    Valentijn The Diabolic Logic

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    I think it's used pretty commonly in autoimmune diseases where there isn't a more specific treatment available yet.
     
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  13. Sasha

    Sasha Fine, thank you

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    You'd think loads of us would be on it, then, given what the rtx trials suggest! :)
     
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  14. Graham

    Graham Senior Moment

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    The synacthen test determines whether your adrenal gland is working properly. I had the test, and mine is, but whenever I cut the dose down much below 10mg I get intense sinus-type headaches and have more fatigue. My ME erupted after a sinus operation. I have this belief (which causes that "look" from doctors) that the inherent infection is still lying there dormant somewhere, and the steroids keep the inflammation down.
     
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  15. JamBob

    JamBob Senior Member

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    For autoimmune diseases they usually use steroids like pred that have a longer half life and are better for quelling inflammation. HC has a shorter half life and has greater mineralcorticoid effects.

    I'd say HC isn't without a number of risks and side effects. It certainly doesn't replicate normal cortisol production and you feel peaks and troughs throughout the day with each dose you take. Researchers are starting to find that cortisol is physiologically released with ultradian pulses and the way that HC pills deliver cortisol doesn't match normal physiology, impacting on things like energy, mood, genes and memory. HC affects your insulin sensitivity and can impact on your sleep. Also it leads to problems every time I get an infection (which is frequent) as you literally feel like you are dying when you have relative adrenal insufficiency (dropping blood pressure, severe weakness etc.) just for a simple infection. I am dependent on other hormone replacement drugs (like insulin) but HC is definitely the worst one I take in terms of "normalising" me.

    I've been on it for 7 years now. I think even if my adrenal glands were partially working when I started it, they won't be now due to suppression from the steroids. At the time I started I was desperate and dying but if there had been other options like RTX - I would have gone for that first.
     
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  16. Graham

    Graham Senior Moment

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    I know my situation is different, JamBob, but I have been on 10mg of prednisolone for 10 years, and had the synacthen test a couple of years back. My adrenal glands were functioning pretty well. So I think it depends on the dosage rather than the length of time. I did read one report that reckoned doses of 10mg or below were not considered to have side-effects, and that has been pretty much true for me.

    In order to take the test, I had to come off the steroids over the course of a week: the headpain after the test was horrific, and continued until I went back on the steroids.
     
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  17. panckage

    panckage Senior Member

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    Yes and going further just because a medication doesn't have a tick mark it doesn't mean it was found ineffective.

    For example with dexedrine it says that it found an effect for fatigue but not for cognition. I find this hard to believe, I think it's likely only fatigue was measured while cognition was not
     
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  18. Bob

    Bob

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    Yes, you're right, panckage - the tick mark simply indicates which features of the illness were measured/assessed in the particular study.
     
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  19. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    I agree with Bob. Labelling Rituximab "moderately effective" doesn`t really get across that a couple of patients got almost healthy again.
     
  20. Graham

    Graham Senior Moment

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    Really the table needed tick, cross and blank.
     
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