Wednesday, 15 November 2017

LDN does not affect MS

"Low dose naltrexone (LDN) has become a popular off-label therapy for multiple sclerosis (MS). A few small, randomized studies indicate that LDN may have beneficial effects in MS and other autoimmune diseases. If proven efficacious, it would be a cheap and safe alternative to the expensive treatments currently recommended for MS. We investigated whether a sudden increase in LDN use in Norway in 2013 was followed by changes in dispensing of other medications used to treat MS."


Raknes G, Småbrekke L.Low dose naltrexone in multiple sclerosis: Effects on medication use. A quasi-experimental study. PLoS One. 2017 Nov 3;12(11):e0187423

We performed a quasi-experimental before-and-after study based on population data from the Norwegian Prescription Database (NorPD). We included all patients that collected at least one LDN prescription in 2013, and had collected at least two medications with a reimbursement code for MS, or collected a medication with MS as the only indication in 2009 or 2010. Outcomes were differences in cumulative dispensed doses and incidence of users of disease modifying MS therapies, and medications used to treat MS symptoms two years before and two years after dispensing the initial LDN prescription. 

The eligible 341 patients collected 20,921 prescriptions in the observation period. Apart from changes in line with general trends in MS therapy in Norway, there was no difference in either dispensed cumulative doses, nor number of prevalent users of MS specific medication. Initiation of LDN was not followed by reductions of other medications used to treat symptoms associated with MS.

LDN is a treatment tried by many but there is no clear evidence of whether it works. This study looked at the treatments taken after LDN and it was not reduced, so there is no evidence for LDN-induced benefit. 

10 comments:

  1. LDN helps patients with fatigue and mood and even if this is not an actual improvment on MS, patients should be respected when they choose to use it. For them it is something.

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    1. I do respect...but there is also duty to question value...I wish a proper study was done and said yeah or neah.

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    2. Low Dose Naltrexone for Treatment of Multiple Sclerosis
      A Retrospective Chart Review of Safety and Tolerability
      LETTER TO THE EDITORS—RESEARCH REPORT
      Journal of Clinical Psychopharmacology • Volume 35, Number 5, October 2015 www.psychopharmacology.com 609
      Excerpts below are from Dr. Anthony Turel’s (Penn State) report:

      To the Editors:

      A potential alternative or adjunctive therapy for MS is related to knowledge about the endogenous opioid system and its ability to modulate autoimmune diseases using animal models of MS. This novel biological pathway involves an endogenous opioid growth factor, chemically termed methionine enkephalin, and its nuclear-associated receptor, Opioid growth factor receptor. Modulation of this pathway by exogenous administration of opioid antagonists such as naltrexone (NTX) has been shown to mediate cell replication including T lymphocytes, astrocytes, and other glia that are associated with MS inflammation and degeneration. The magnitude and direction of change in cell proliferation is dependent on the duration of opioid receptor blockade. Low dosages of NTX (LDN), given once daily, block the receptor intermittently and result in inhibited cell replication. The LDN treatment of mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS, improves the course of progressive EAE. Mice immunized with myelin oligodendrocytic glycoprotein to establish EAE and treated daily with 0.1 mg/kg NTX (LDN) beginning at the time of disease induction show delayed onset of clinical disease and reduced behavioral deficits. Pathology of the spinal cord from these mice revealed significant reductions in the number of activated astrocytes and area of demyelination. The LDN treatment of mice with established relapsing-remitting EAE revealed that endogenous opioids inhibited progression of the disease as well.

      The medical records of 215 MS patients, aged 18 to 65 years, seen in the MS clinic for a 7-year period (January 01, 2005 to May 31, 2012) and prescribed 3.5 mg LDN, orally, once daily, served as the study group.

      Prescriptions for LDN were provided to 152 female (71%) and 63 male (29%) patients... Seventy seven percent (n = 166) of patients taking LDN for any period of time did not report any side effects. Six percent of the patients had insomnia, whereas 5% of the patients had excessive dreams. There was no evidence of increased side effects related to other immunomodulators when combined with LDN. No abnormal laboratory results were noted. Of the 215 patients receiving LDN, 57 patients (26%) were hospitalized during the duration of this study; 48 of these patients were hospitalized for non-MS–related events such as infections. No patient was admitted to the hospital because of side effects of LDN.

      Most of the MS patients began LDN therapy because of fatigue. Nearly 60% (n = 128) of patients receiving LDN for any period of time reported a reduction in fatigue with LDN therapy. Fifty of the 215 patients commented that LDN produced no relief from fatigue and 4 patients stated that LDN increased their fatigue levels. Regarding their quality of life and the perception of LDN's effects on MS, 130 patients (60%) stated that LDN stabilized or improved their disease and 75% of the patients reported improved or stabilized quality of life. Nine patients reported that LDN reduced the quality of life, and 8% of the patients had the perception that their disease increased while on LDN but provided no details.


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  2. Research into LDN and multiple sclerosis (from the MS Trust website), the first paragraph below mentions "There was a significant reduction in spasticity during the trial, but half the participants reported an increase in pain "

    "A study in Milan involved 40 people with primary progressive MS taking 4mg/day LDN for six months. The results showed LDN was safe and well tolerated. There was a significant reduction in spasticity during the trial, but half the participants reported an increase in pain. There were no significant changes to measures of fatigue, depression or quality of life.

    A study at the University of California looked at the effects of LDN on quality of life in 80 people with MS. Results showed LDN significantly improved quality of life (specifically mental health, pain, and self-reported cognitive function.) However, no impact was observed on symptoms such as fatigue, bowel and bladder control, sexual satisfaction and visual function. Vivid dreaming was reported during the first week of treatment, but no other adverse effects were reported.

    A second study of quality of life in 96 people with relapsing and secondary progressive MS found that there were no significant differences on a wide range of quality of life measures between those taking placebo and those taking LDN for 17 weeks.

    A small study comparing people who took LDN only or Copaxone with or without LDN found that scores for timed walk tests, MRI data and liver enzyme levels were similar. LDN was shown to be safe and well tolerated. The study was primarily looking at LDN safety in the long-term rather than at efficacy."

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  3. Strange argument, based on a very indirect measure of effect on MS. Interestingly, it holds for every licenced MS treatment: Since there is always need for therapy switch or escalation, none of them treatments affects MS.

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  4. I was pretty sceptical about LDN but gave it a try and while I was hoping for a positive impact on my fatigue this didn't happen. What did happen (and very rapidly) was a significant improvement in my sleep patterns and a very noticeable reduction in night-time visits to the toilet, as well as a general reduction in bladder urgency.

    As LDN can be taken alongside pretty well every other prescribed drug for MS, and has no side effects other than some irritating ones (e.g. vivid dreams) there is no particular reason why use of LDN would necessarily have an impact on the number of prescriptions filled for standard MS drugs.

    I agree that solid and extensive evidence of the efficacy or otherwise of LDN is thin on the ground. However, to assert that there is no evidence for LDN having any benefits in MS on the basis of "no change" in prescription filling for MS drugs is really drawing a bit of a long bow, and how this study ever even got off the ground is beyond me. Mousedoctor - for you to state (based on the conclusions of this study) that "there is no evidence for LDN-induced benefit" makes it seem like your usual scientific rigour on correlation and causation has deserted you on this occasion.
    http://www.tylervigen.com/spurious-correlations

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    1. "Your usual scientific rigour on correlation and causation has deserted you on this occasion".

      Yes I agree.....I was interested in the debate. I was expecting alot of people to tell me how wrong I was.

      I think it is something that should researched and the subject should put to bed or not. There are so many people with MS taking this agent surely they need some answers whether there is any merit.

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  5. What I understand from reports of people using LDN is that it improves symptoms related to MS (fatigue, spasticity, sleep problems, etc.) but it doesn't seem to have any effect on the number of relapses of the disease.

    I even think that pwMS that use vitamin D above 10.400 IU consistently have fewer relapses of MS than those who use LDN.

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  6. Isn't LDN just another placebo, but a harmless and cheap one? Placebos have benefits for people who believe in them so what's the problem with a harmless, cheap placebo? I don't think the NHS should pay for it without a big, properly run (double-blind, placebo controlled) study. And no-one's going to pay for that, you would think. Although I've had MS long enough to remember the big, double-blind, placebo controlled study on cannabis which showed that it did ... nothing for progression. Cannabis was the LDN of its day.
    I agree with Cinara about Vitamin D but I don't think it's been proved, has it?

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    1. Can I point out that in the cannabis trial....the placebo effect killed the idea. People on the trial did relatively well and did not progress at the predicted rate, so it was not possible to show a treatment effect in the overall population in the subgroup analysis in the people below EDSS 5.5 who were progressing, THC had a significant effect. However as the trial took over 5 years to do no one is going to go back to do it again...End of a research line for us.

      VitD....Studies are ongoing.

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