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

Beyond

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

I am going to start Amitryptiline this night. Yeah, apparently it causes commonly heartbeat problems from what I have been reading. Heart problems are pretty scary, have only experienced them once.

Other candidates are: Mirtazapine, Clonidine, Ritanserin, maybe Quetiapine.
 

snowathlete

Senior Member
Messages
5,374
Location
UK
I am going to start Amitryptiline this night. Yeah, apparently it causes commonly heartbeat problems from what I have been reading. Heart problems are pretty scary, have only experienced them once.

Other candidates are: Mirtazapine, Clonidine, Ritanserin, maybe Quetiapine.
good luck. be warned: you will feel like s**t for at least a week when you start this drug. It does pass - at least it did for me.
 

frederic83

Senior Member
Messages
296
Location
France
After a few days on it, I'm a bit more tired 1 hour after the dose but I don't sleep. Then the sleepiness vanishes and I'm wide awake, as usual. I wait a few hours to see if something else happens. Then it is 6 am and I finally take my melatonine otherwise I don't sleep. I will try it for a week or so, I don't think it is that powerful.
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
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
Did you ever try this one, @Hip?
 

boolybooly

Senior Member
Messages
161
Location
Northants UK
I wonder what the effect is on the immune system?

We need subtype recognition. Not all CFS is the same type.

ME CFIDS is characterised by immune dysfunction. My own condition includes sleep disturbance but also regular, cyclic and unrelenting recurrent virus activity.

Anything which causes me excitement and "adrenalin" tends to shorten the cycle of recurring virus attacks due to the suppressive effect on immunity and also creates an ME backlash of an unknown cause but which could relate to the raised immune challenge resulting from transient immune suppression.

Since norepinephrine has this kind of an immunosuppressive effect it strikes me this may not be an appropriate intervention for some people with CFIDS. Stimulants are generally not good for CFIDS patients in the mid to long term.

If you think about it, its precisely because stimulation diverts energy from immunity to activity that it perks people up. That is its biological function and evolutionary purpose and the driver of the evolution which created norepinephrine as a cognitively initiated molecular signal. Its also why people in an immune crisis feel lousy.

Energy economics is a key concept in biology. There is no such thing as a free lunch and if you divert energy away from immune activity you pay a price. I can only suggest that people be careful, it might help some but not others.

I have found that sleep hygiene helps i.e. when using a computer or watching TV, dont do it within three hours of sleeping. Also conscious relaxation and awareness of muscular and mental tension can help but you have to persist with it so it becomes second nature to relax and not allow tension to build up.
 
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Ema

Senior Member
Messages
4,729
Location
Midwest USA
I wonder what the effect is on the immune system?

ME CFIDS is characterised by immune dysfunction. My own condition includes sleep disturbance but also regular, cyclic and unrelenting recurrent virus activity.

.

Improving the circadian rhythm with agomelatine, as per the article posted above, could be a really *good* thing for the immune system.

In the new study, researchers set out to further unpack the connection between immunity and the body’s clock by examining whether a key immune system gene — the so-called “Toll-like receptor 9” gene — is under circadian control and, if so, what that might mean for immune system function, including defense against infection.

Using mice, the researchers found that when levels of that particular gene were highest, the mice were better able to withstand infections. The results were published online Wednesday in the journal Immunity.

“What we discovered is that this innate immune gene is under circadian rhythm,” Adam C. Silver, a postdoctorate associate in infectious diseases at Yale and one of the study’s authors, told The Huffington Post.

https://www.huffingtonpost.com/2012/02/16/circadian-rhythms-immunity-immune-system_n_1281654.html

This article also challenges the idea that NE is always suppressive to the immune system.

Abstract
A common dogma has been that norepinephrine (NE) suppresses lymphocyte function. However, recent studies have challenged this dogma, showing that NE also enhances immune cell readiness during infection and immune challenge.
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
Improving the circadian rhythm with agomelatine, as per the article posted above, could be a really *good* thing for the immune system.



This article also challenges the idea that NE is always suppressive to the immune system.
So this one seems to be a winner for me. I feel “brighter” in general and have started waking up naturally before 8AM again.

It hasn’t really helped my subjective sleep at all (I still am restless) though my Ōura ring suggests my deep sleep has increased from 1-12 min range to 40-50.

Anyway, more positives than negatives for me, for now anyway.
 
Messages
79
Location
Seattle
I stopped taking Agomelatine four days after starting (four doses, total) due to an adverse reaction - it caused severe migraines for me. I had a migraine within 3 hours of taking it starting on days 2, 3, and 4. Migraine is listed as one of the documented possible adverse events for the drug. I wish it was not so as I found the effect useful. It’s also odd that there are recent studies suggesting Agomelatine’s use in prophylactically treating migraine. And it really sucks as three nights of migraine have caused a fairly bad crash (as I am sure you can imagine).

I wonder if the migraine is due to the drug itself or some other ingredient used in the pill. It’s a yellow pill, made by Servier, and I got it from Rupharma which has a good reputation (that I know of) and the pill and packaging look quite legit. I have ordered other items from Rupharma that were legitimate.
I think that if you don’t have adverse side-effects then it’s worth a try - as long as you have a liver panel for elevated AST/ALT to make sure that you don’t suffer from the liver enzyme problem that is the main negative side-effect - and the reason why the FDA hasn't approved it for the US. I wish it would have worked out…
 

nandixon

Senior Member
Messages
1,092
I stopped taking Agomelatine four days after starting (four doses, total) due to an adverse reaction - it caused severe migraines for me.
Thanks for posting your experience. Taking melatonin causes migraines for me at any dosage from 3 mg down to 0.3 mg, so I'd been reluctant to try agomelatine which has a very similar chemical structure. Does melatonin give you migraines as well?
 
Messages
79
Location
Seattle
Thanks for posting your experience. Taking melatonin causes migraines for me at any dosage from 3 mg down to 0.3 mg, so I'd been reluctant to try agomelatine which has a very similar chemical structure. Does melatonin give you migraines as well?

hi @nandixon, i have been taking a 5 mg immediate/extended-release melatonin (natrol brand) for the last year and, in fact, my migraines have lessened greatly. in researching agomelatine, i noticed that there are also studies showing efficacy for melatonin in migraine prophylaxis. i wonder if the melatonin is responsible for reducing my migraines?

it's interesting that it causes migraines for you - we are all so different.

i guess it's possible that agomelatine interfered with the melatonin's purported prophylactic action in this regard? i don't think there are definite answers.