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A randomised, placebo-controlled, double-blinded trial of duloxetine in the treatment of general fatigue in CFS, 2014, Arnold et al. Cymbalta

Discussion in 'BioMedical ME/CFS Research' started by Hutan, Jan 15, 2020.

  1. Hutan

    Hutan Moderator Staff Member

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    https://www.sciencedirect.com/science/article/abs/pii/S0033318214001935?via=ihub
    https://doi.org/10.1016/j.psym.2014.12.003

    Lesley Arnold, Thomas Blom, Jeffrey Welge, Elizabeth Mariutto, Alicia Heller
    Women’s Health Research Program, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH

    Published in the journal Psychosomatics
    Objective
    To assess the efficacy and safety of duloxetine in patients with chronic fatigue syndrome.

    Methods
    A 12-week, randomized, double-blind study was designed to compare duloxetine 60–120 mg/d (n = 30) with placebo (n = 30) for efficacy and safety in the treatment of patients with chronic fatigue syndrome.

    The primary outcome measure was the Multidimensional Fatigue Inventory general fatigue subscale (range: 4–20, with higher scores indicating greater fatigue).

    Secondary measures were the remaining Multidimensional Fatigue Inventory subscales, Brief Pain Inventory, Medical Outcomes Study Short Form-36, Hospital Anxiety and Depression Scale, Centers for Disease Control and Prevention Symptom Inventory, Patient Global Impression of Improvement, and Clinical Global Impression of Severity.

    The primary analysis of efficacy for continuous variables was a longitudinal analysis of the intent-to-treat sample, with treatment-by-time interaction as the measure of effect.

    Results
    The improvement in the Multidimensional Fatigue Inventory general fatigue scores for the duloxetine group was not significantly greater than for the placebo group (P = 0.23; estimated difference between groups at week 12 = −1.0 [95% CI: −2.8, 0.7]).

    The duloxetine group was significantly superior to the placebo group on the Multidimensional Fatigue Inventory mental fatigue score, Brief Pain Inventory average pain severity and interference scores, Short Form-36 bodily pain domain, and Clinical Global Impression of Severity score. Duloxetine was generally well tolerated.

    Conclusion
    The primary efficacy measure of general fatigue did not significantly improve with duloxetine when compared with placebo. Significant improvement in secondary measures of mental fatigue, pain, and global measure of severity suggests that duloxetine may be efficacious for some chronic fatigue syndrome symptom domains, but larger controlled trials are needed to confirm these results.
     
  2. Hutan

    Hutan Moderator Staff Member

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    from https://www.medicinenet.com/duloxetine (known as Cymbalta):
    Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressants used for treating depression, anxiety disorder, and pain. Other drugs in this class include milnacipran (Savella), venlafaxine (Effexor), and desvenlafaxine (Pristiq). Duloxetine affects neurotransmitters, the chemicals that nerves within the brain make and release in order to communicate with one another. Neurotransmitters either travel across the space between nerves and attach to receptors on the surface of nearby nerves or they attach to receptors on the surface of the nerves that produced them, to be taken up by the nerve and released again (a process referred to as re-uptake).

    Many experts believe that an imbalance among neurotransmitters is the cause of depression as well as other psychiatric disorders. Serotonin and norepinephrine are two neurotransmitters released by nerves in the brain. Duloxetine works by preventing the reuptake of serotonin and epinephrine by nerves after they have been released. Since uptake is an important mechanism for removing released neurotransmitters and terminating their actions on adjacent nerves, the reduced uptake caused by duloxetine increases the effect of serotonin and norepinephrine in the brain. The mechanism responsible for its effectiveness treating pain is not known but also is thought to involve its effects on serotonin and norepinephrine in the brain. Duloxetine was approved by the FDA in August 2004.

    Duloxetine is approved for treating the following conditions:

     
  3. Arnie Pye

    Arnie Pye Senior Member (Voting Rights)

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  4. JES

    JES Senior Member (Voting Rights)

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    Cymbalta is commonly prescribed for management of neuropathic pain, so it's not surprising to me that it would reduce "pain" in ME/CFS and with less pain one might be able to sleep better, hence less fatigue. Probably little useful to treat the core pathology in ME/CFS though. And yes, Cymbalta has withdrawal problems, but if there is a treatment that works I would be on it for life and wouldn't need to withdraw from it, so I never understood this argument.
     
  5. kilfinnan

    kilfinnan Established Member

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    I was prescribed Cymbalta. It was a horrible experience. I found it almost impossible to stop due to withdrawals. 18 months! The worst symptom for me was a short intense feeling of only what I could describe as vertigo. Suppose that's what some people describe as 'brain zaps'. Constantly feeling travel sick.

    I'm at a point now, of desperation but personally I wouldn't do it again. That's only my experience but I would caution anyone who would consider Cymbalta, be aware.
     
  6. Invisible Woman

    Invisible Woman Senior Member (Voting Rights)

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    I've tried it among a list a SSRIs and SNRIs I've tortured myself with in attempts to get better. I've always been completely clobbered by side effects even at minimal doses. No benefits.

    I would agree but....

    It isn't unknown to get to the optimal dose of drugs like this, have some improvement in pain, sleep, etc., but then find the drug stops working for you. A situation can develop where you simply cannot tolerate any increase in dose, the current dose doesn't work and you have great difficulty weaning off it.

    This happened to a friend with ME. Admittedly it wasn't Cymbalta, but it was a drug I had tried and couldn't tolerate. I was quite envious at first but then it stopped working for and she went through hell trying to get off it.

    It's not really advisable to keep taking a drug that doesn't help you anymore, as any side effects that may have been worth it are now an additional burden. It might also increase the likelihood of problems with drug interactions or complications further down the line.
     
    alktipping, MeSci, MEMarge and 10 others like this.
  7. shak8

    shak8 Senior Member (Voting Rights)

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    I won't take any antidepressants of the newer variety (SSRI, etc). I tapered off Paxil too fast and it provoked a type of mania (not meeting the threshold of mania, but still very weird and disconcerting to those around me and me, also), according to a shrink I consulted.

    I have primarily fibromyalgia pain or some sort of initially thought to be auto-i
    immune disorder induced pain. Don't need anything that is stimulative mentally.

    Edit: Dr. Leslie Arnold has done many clinical trials with this drug. Ad nauseum?
     
  8. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    All of the other findings they they are claiming are "statistically significant" don't survive corrections for multiple comparisons (meaning if there is an effect, that effect is weak).
     
  9. James Morris-Lent

    James Morris-Lent Senior Member (Voting Rights)

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    sci-hub: https://sci-hub.tw/https://www.sciencedirect.com/science/article/abs/pii/S0033318214001935?via%3Dihub

    With just one treatment group that is receiving 'flexible dosing', I would be worried about the efficacy of blinding. I would think this would call for a dose-response design.

    Maybe more importantly, I thought antidepressants were a well-known dead-end in ME/CFS? Other than for the important use of treating depressed patients' depression; and maybe insomnia, or possibly pain, depending on the particular drug. Goodness knows how many patients have received various antidepressants over the years so I have to think we would have gotten on to it one of them was particularly effective.
     
  10. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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  11. lansbergen

    lansbergen Senior Member (Voting Rights)

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    They probebly are right but looking at the wrong substance.
     
    alktipping likes this.
  12. ProudActivist

    ProudActivist Senior Member (Voting Rights)

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    I wish such a lifelong treatment could be found! In my experience, our bodies change and can become intolerant of drugs over time even if they still work to some extent. As we age some are more risky as well. I have yet to find more than a couple of drugs I can take long term (so far) and not find in the end I am better off without them, despite a good start and often a few years of usefulness.

    also, as I understand it (and from unreferenced websites) drugs like this deplete vitamin and minerals which we need, often for the very problem they treat. So they can cause problems that way long term.

    After decades of being pushed drugs, particularly anti-depressants in the early years, I now try to take as little as possible. I wouldn’t take anything for “fatigue “ as I agree, there is no understanding of the mode of action or cause of this nebulous symptom. Also I can cope with it more easily than pain, or POTS symptoms, which are more difficult.

    after greatly reducing gabapentin and having a very hard time with the withdrawal I wouldn’t touch Cymbalta, personally. I just hope my pain stays manageable and I don’t have to try more drugs.
     
  13. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    Which begs the question, what is the right substance? Or more appropriately, how would we find out what the right substance is?
     
    lansbergen likes this.
  14. lansbergen

    lansbergen Senior Member (Voting Rights)

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    Looking at what happened with the animals after the mysterious chronic infection was brought in I would say look at the neurotransmitter achetylcholine and receptors.

    As the allosteric a7nicotine achetylcholine receptor modulator was the med to treat the animals with and it also saved my live and still helps me I would say start there. It not only eases the pain within 10 minutes but also calms my brain.
     

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