The End ME/CFS Project: History Taking Root
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Agomelatine but not melatonin improves fatigue perception: a longitudinal proof-of-concept study

Discussion in 'Latest ME/CFS Research' started by MikeJackmin, Mar 1, 2014.

  1. MikeJackmin

    MikeJackmin

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    http://www.sciencedirect.com/science/article/pii/S0924977X14000686

    Agomelatine but not melatonin improves fatigue perception: a longitudinal proof-of-concept study

    Abstract

    Chronic Fatigue Syndrome (CFS) represents a disabling condition characterized by persistent mental and physical fatigue, bodily discomfort and cognitive difficulties. To date the neural bases of CFS are poorly understood, however mono-aminergic abnormalities, sleep-wake cycle changes and prefrontal dysfunctions are all thought to play a role in the development and maintenance of this condition. Here we explored in a group of 62 CFS subjects the impact on fatigue levels of agomelatine, an antidepressant with agonist activity at melatonin receptors (MT1 and MT2) and antagonist activity at serotoninergic 2C receptors (5HT2C). To tease out the relative effects of MT-agonism and 5HT2C antagonism on fatigue, we compared agomelatine 50 mg u.i.d. with sustained release melatonin 10 mg u.i.d. in the first 12-week-long phase of the study, and then switched all melatonin-treated subjects to agomelatine in the second 12-week-long phase of the study. Agomelatine treatment, but not melatonin, was associated with a significant reduction of perceived fatigue and an increase in perceived quality of life. Moreover the switch from melatonin to agomelatine was associated with a reduction of fatigue levels. Agomelatine was well tolerated by all enrolled subjects. Our data, albeit preliminary, suggest that agomelatine treatment could represent a novel useful approach to the clinical care of subjects with CFS.
     
    NK17 likes this.
  2. adreno

    adreno Senior Member

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    5-HT2C antagonism causes release of dopamine and norepinephrine in the brain.
     
    Beyond likes this.
  3. CFS_for_19_years

    CFS_for_19_years First Do No Harm

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    Trade names are Valdoxan, Melitor and Thymanax.
    I'll ask about this at my next psych visit. Thanks for posting.

    ETA: Did not realize it's not available in US. Can be purchased online at Canadian pharmacies if you can afford it.
     
    Last edited: Mar 1, 2014
  4. NK17

    NK17 Senior Member

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    Thank you for bringing this up!

    Agomelatine is indeed a very interesting molecule and innovative drug with the big advantage of regulating circardian rythms and its ability to improve disrupted sleep patterns, without being sedating during the day.

    Sounds like the magic pill for many of us ;).

    I stumbled upon it while researching new types of drugs and even managed to get a small supply from Europe.

    This was back in 2011, back then there were preliminary rumors about the approval by the FDA for the US market.
    From a preliminary research it seems that it's still not available in the US.

    Of interest is the research done by Dr. Christian Guilleminault from Stanford University Sleep Disorders Clinic in California.

    I did not experiment with it, I still have the 2 boxes, which by now have experied ;(.

    All this makes me want to reach Dr. Guilleminault and put him in contact with Dr. Montoya at Stanford, one of the few doctors/researchers that is working tirelessly for PWME.
     
  5. lnester7

    lnester7 Seven

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  6. adreno

    adreno Senior Member

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    Perhaps, but there are different forms of POTS, and some are helped by increased NE. I doubt it's a very strong effect, anyway.
     
  7. xchocoholic

    xchocoholic Senior Member

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    10 mg of melatonin is waaaay too much for me. My max during an episode of insomnia caused by gluten, caffeine and stress was 9 mg. I needed 5htp and theanine or klonopin too tho. And that left me feeling groggy for 2 days.

    I'm currently experimenting with .33-1 mg. So far I'm ok with taking it for 1-2 nights in a row but no longer than that.

    I don't know why they gave pwcs such a high dose of melatonin. We're known for needing less not more.

    Tc ... x
     
  8. snowathlete

    snowathlete

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    This was one if three drugs recommended by my sleep specialist following a sleep study a few years back.
    I've been on amitriptyline which worked really well for sleep but has been wearing off. Saw my GP today and she has upped the dose again...but I am suspicious that it's been responsible for my heavy and fast heartbeat. If it makes that worse then I'll be trying one of the other two probably.
     
  9. Hip

    Hip Senior Member

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    Sounds very interesting, and I think I am going to try this drug. Pity it is a bit on the expensive side. Prices are around $110 for 25 x 25 mg tablets, but with some pharmacies like www.aurapharm.com selling as cheap as $57 (but I read that www.aurapharm.com has a bad reputation, so it may be best avoided).

    Some agomelatine suppliers:
    Treat Depression With Agelomelatine
    Search results :: United Pharmacies (UK)
    Valdoxan (Agomelatine) - United Pharmacies
    Buy Agomelatine Valdoxan Online No Prescription 25mg 28 Tablets
    Valdoxan (Agomelatine) tablets
    Buy Valdoxan (Agomelatine) 25mg
    Agomelatine 25mg at $2.42 per Tablet
    AURAPHARM - agomelatine
     
  10. NK17

    NK17 Senior Member

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    @snowathlete and @Hip I would consider that on 24 September 2014 the EMA European Medicines Agency (the equivalent of the FDA in the US, but with more independency from big pharma and I dare say more transparency and integrity ;)) has raised concerns regarding agomelatine (sold under the 2 brand names Valdoxan and Thymanax) for its potential serious liver toxicity.

    The EMA stated that strict liver function monitoring is to be done during treatment with agomelatine (Valdoxan, Thymanax).

    A patient booklet will be distributed to all patient taking this drug and doctors have been alerted and informed as well.

    Liver functioning tests should be performed before and during the treatment with the drug.
     
    Last edited: Nov 6, 2014
    snowathlete, Hip and CFS_for_19_years like this.
  11. adreno

    adreno Senior Member

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    Kudzu is a herbal with 5-HT2C antagonistic mechanism. It might be interesting to combine it with melatonin, to emulate the effects of agomelatine.
     
  12. Snow Leopard

    Snow Leopard Senior Member

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    I'd like to see these results replicated, but specifically I'd like to see whether patients can actually increase their activity levels, or improve performance on neuropsychiatric tests.

    I mean patients are interested in being able to do more without extra symptoms, not ticking different boxes on questionnaires.

    This is not the first drug shown to have this sort of effect on patients, likely mediated by increased dopamine, others include dextroamphetamine, methylphenidate, L-deprenyl. But few recommend those to treat CFS.
     
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  13. Hip

    Hip Senior Member

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    And in particular, 5-HT2C antagonism releases dopamine in the prefrontal cortex, according to this article: 5-HT2C receptor - Wikipedia

    In ADHD, dopamine is low in the prefrontal cortex. The virus I caught which triggered my ME/CFS also hit me with an episode of viral meningitis, causing some brain damage, after which I developed severe ADHD. So it will be interesting to see if agomelatine can help both my ME/CFS and ADHD. One study found agomelatine to be useful in ADHD.

    I have just ordered some agomelatine to try.
     
  14. Hip

    Hip Senior Member

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    One interesting property of agomelatine is that it can restore the circadian rhythm:

    Agomelatine as chronopsychopharmaceutics restoring circadian rhythms and enhancing resilience to stress: a wishfull thinking or an innovative strategy for superior management of depression?

    Given the significant circadian rhythm disruptions in ME/CFS patients, I wonder if agomelatine might be able to reset our clocks. I have a strong tendency to sleep cycle inversion, where you sleep during the say and are awake during the night. It would be great if agomelatine could restore normality in my aberrant circadian rhythm.
     
    Last edited: Nov 7, 2014
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  15. CFS_for_19_years

    CFS_for_19_years First Do No Harm

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    Agomelatine for the treatment of patients with fibromyalgia and depressive symptomatology: an uncontrolled, 12-week, pilot study.
    http://www.ncbi.nlm.nih.gov/pubmed/24549860
    Agomelatine in the treatment of fibromyalgia: a 12-week, open-label, uncontrolled preliminary study.

    http://www.ncbi.nlm.nih.gov/pubmed/23764682

     
    Last edited: Nov 8, 2014
  16. adreno

    adreno Senior Member

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    That doesn't sound very impressive.
     
  17. kisekishiawase

    kisekishiawase sad

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    This drug is a melatonin receptor agonist like ramelteon.
    Anyone with tachycardia or dysautonomia have tried it? I wonder since it says it increases norepinerphrine , it would cause excitation.
     
  18. Little Bluestem

    Little Bluestem Senescent on the Illinois prairie, USA

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    Maybe to make the agomelatine look better by comparison.
     
  19. Beyond

    Beyond Juice Me Up, Scotty!!!

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    And that´s how these drugs cause REM suppression to various degrees, that is related to a pararell increase in SWS. I mean, just speculation and generalization from my part. Been reading a lot on sleep drugs and their effect in sleep for my specific problem which seems tied to excessive REM and low deep stages.
     
    Last edited: Jan 29, 2015
  20. Beyond

    Beyond Juice Me Up, Scotty!!!

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    The thing with agomelatine is that it looks good in paper, but empiric reports in places like longecity or drugs.com don´t put it in such a favourable light. It lookes pretty failed in fact.

    Maybe something else to try I guess.
     
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