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

MikeJackmin

Senior Member
Messages
132
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.
 

CFS_for_19_years

Hoarder of biscuits
Messages
2,396
Location
USA
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.
 
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NK17

Senior Member
Messages
592
Trade names are Valdoxan, Melitor and Thymanax.
I'll ask about this at my next psych visit. Thanks for posting.

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.
 

xchocoholic

Senior Member
Messages
2,947
Location
Florida
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
 

snowathlete

Senior Member
Messages
5,374
Location
UK
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.
 

Hip

Senior Member
Messages
17,824
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
 

NK17

Senior Member
Messages
592
@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.
 
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Snow Leopard

Hibernating
Messages
5,902
Location
South Australia
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.
 

Hip

Senior Member
Messages
17,824
5-HT2C antagonism causes release of dopamine and norepinephrine in the brain.

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.
 

Hip

Senior Member
Messages
17,824
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.
 
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CFS_for_19_years

Hoarder of biscuits
Messages
2,396
Location
USA
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
Abstract
INTRODUCTION:
Agomelatine, a melatonin agonist and selective 5-HT2C antagonist, is a novel antidepressant with sleep-enhancing properties. The purpose of this study was to assess the efficacy and tolerability of agomelatine among patients with fibromyalgia and depression.

METHODS:
23 patients with fibromyalgia and depressive symptomatology received 25-50 mg of agomelatine daily for 12 weeks. The primary outcome measure was the change of the Beck depression inventory score. Secondary outcome measures included the hospital anxiety and depression scale, Pittsburgh sleep quality index, Fibromyalgia Impact Questionnaire, short-form health survey, brief pain inventory and patient's global impression scale.

RESULTS:
Agomelatine significantly improved depression, global fibromyalgia severity and pain intensity but effect sizes were small. No improvement was seen in sleep quality. Patients categorized as responders to treatment had milder disease severity than non-responders. Agomelatine therapy was well tolerated and patients only reported mild and transient side effects.

DISCUSSION:
Agomelatine slightly improved depressive and fibromyalgia symptomatology but did not improve sleep quality. Our data do not support agomelatine as a first-line treatment option for the treatment of fibromyalgia and depression.

Agomelatine in the treatment of fibromyalgia: a 12-week, open-label, uncontrolled preliminary study.

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

Abstract
Pharmacological therapy for fibromyalgia syndrome (FMS) is actually unsatisfactory; analgetic and nonsteroidal anti-inflammatory drugs are not very effective. On the other hand, it is opportune to underline that antidepressant drugs produce positive response on pain in patients with FMS. Furthermore, many studies showed that using variable doses of melatonin (3-6 mg/d) in subjects affected from FMS had significantly been effective on pain, sleep, daytime fatigue, and depression. This study was aimed to evaluate the efficacy of agomelatine on depression, anxiety, cognition, and pain in a sample of drug-free FMS patients. Agomelatine was administered at the single daily dose of 25 mg/d to 15 fibromyalgia "drug-free" female subjects during 12 weeks. .......... Treatment with agomelatine significantly improved depression, anxiety, and pain in patients with FMS. Regarding executive/cognitive symptoms, treatment with agomelatine did not have a significant impact on the explored neuropsychological domains, although there was a trend toward the improvement of performances. The findings showed that agomelatine was effective and well tolerated in patients with FMS. Further research is needed to fully evaluate the role of agomelatine as a potential pharmacological strategy for the treatment of FMS.
 
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Messages
426
Location
southeast asia
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.
 

Beyond

Juice Me Up, Scotty!!!
Messages
1,122
Location
Murcia, Spain
5-HT2C antagonism causes release of dopamine and norepinephrine in the brain.

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.
 
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Beyond

Juice Me Up, Scotty!!!
Messages
1,122
Location
Murcia, Spain
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.

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.