54 replies to this topic

[FunkOdyssey]

Tianeptine's action on serotonin receptors is almost identical to sulbutiamine's action on dopamine receptors, look it up, it doesn't increase the release of serotonin at all, the mechanism is receptor regulated.

I'm not the first person to have the idea:

Neuropsychopharmacol Hung. 2009 Jun;11(2):83-7.
Antidepressant action of tianeptine is connected with acceleration of serotonin turnover in the synapse: a hypothesis.

Uzbekov MG.

Department of Brain Pathology, Research Institute of Psychiatry, Moscow. uzbekovmg@mtu-net.ru
Abstract

Based on the results of our investigation of patients with anxious depression under the treatment with serotonergic antidepressants with different mechanism of action on serotonin reuptake we, the first time in the literature, propose the hypothesis about neurochemical mechanism of tianeptine action. According to this hypothesis tianeptine not only activates serotonin reuptake into the synaptic ending but also activates its release from the ending into the synaptic cleft thus accelerating serotonin turnover rate in the synapse. Proposed mechanism mainly refers the first, acute phase of its action directed to the normalization of serotonergic neurotransmission.

You may be right about agomelatine keeping the 5HT-2C receptors from upregulating substantially in response to the tianeptine's reverse-agonism but since agomelatine has such a gradual and benign effect, and 5HT-2C receptors respond more readily to reverse-agonism I can see it simply being made ineffective.

tianeptine is not an inverse agonist of 5-HT2C receptors, I'm not sure why you keep characterizing it this way.

What I'm saying is that agomelatine is a long term and gradual antidepressant, while tianeptine has primarily short term effects on serotonin, but is extremely potent in comparison. It only has long term effects on D1 + D2 auto-receptors, which are irrelevant to the MOA of agomelatine.

I consider most antidepressants to be gradual and long-term including tianeptine, and indeed it does not reach full effects for 4-6 weeks, underlining the fact that its acute effects, despite the fact that they may be mood-lifting, are not "THE antidepressant effect", which lately researchers seem to think is actually related to glutamate modulation:

Mol Psychiatry. 2010 Mar;15(3):237-49. Epub 2009 Aug 25.
The neurobiological properties of tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation.

McEwen BS, Chattarji S, Diamond DM, Jay TM, Reagan LP, Svenningsson P, Fuchs E.

Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA. mcewen@mail.rockefeller.edu
Abstract

Tianeptine is a clinically used antidepressant that has drawn much attention, because this compound challenges traditional monoaminergic hypotheses of depression. It is now acknowledged that the antidepressant actions of tianeptine, together with its remarkable clinical tolerance, can be attributed to its particular neurobiological properties. The involvement of glutamate in the mechanism of action of the antidepressant tianeptine is consistent with a well-developed preclinical literature demonstrating the key function of glutamate in the mechanism of altered neuroplasticity that underlies the symptoms of depression. This article reviews the latest evidence on tianeptine's mechanism of action with a focus on the glutamatergic system, which could provide a key pathway for its antidepressant action. Converging lines of evidences demonstrate actions of tianeptine on the glutamatergic system, and therefore offer new insights into how tianeptine may be useful in the treatment of depressive disorders.

PMID: 19704408

[FunkOdyssey]

The reuptake effects of tianeptine only last as long as the drug is in your system at active levels, whereas the irreversible antagonism of 5-HT2C receptors by agomelatine lasts well beyond it's half-life, though it's melatonin agonism decreases in proportion to plasma concentration. You're totally wrong about plasma concentration of antidepressants being irrelevant, this may be true in some cases, but not in all. For example, Buproprion requires maintained plasma concentrations to be effective, which is why there is an SR and XR version of the pill, tianeptine is the same.

In order to be totally wrong, my statement would have to be true in no cases.

I simply think you're wasting the agomelatine, and I'm not sure why you're taking both at once when you recently claimed to be fully satisfied with your regime. These are significant additions, and starting them both only weeks apart is irresponsible in my opinion, you haven't even waited for tianeptine to exhibit long term effects. It's not as simple as 'the more antidepressants the better', you should be aiming to be on the least amount of pharmaceuticals necessary to achieve a remission in whatever condition you are suffering from, which in your case is what?

I haven't kept my regimen updated very well on here, I'll update it in the next couple days along with the rationale for all the changes. Briefly, I've done an insane amount of research in the last few weeks regarding the substantial influence of antidepressant and psychostimulant drugs on the immune system, which is important in my case because I have Lyme. I was forced to drop dexmethylphenidate as a result, leaving escitalopram unbalanced by anything dopaminergic. I briefly toyed with the idea of augmenting it with an agonist (ropinirole) but ultimately decided against it, and went back to tianeptine which I've used before. I'll acknowledge the addition of agomelatine after such a short time on tianeptine is a bit hasty but I have prior experience with both drugs so I'm not flying entirely blind.

What I'm trying to treat: mild depression/dysthmia/anhedonia, mild anxiety (more panic than GAD, tianeptine is already controlling this 100%, escitalopram did as well), inattentive ADHD, shitty libido. Most of this is probably secondary to Lyme but I think there's potential for symptomatic treatment anyway. My antibiotic treatment of Lyme is ongoing and supervised by an LLMD.

If you eliminate all antidepressants that negatively affect libido (SSRI's, SNRI's, TCA's, MAOI's) and/or immune function (NRI's, NaSSAs), and all psychostimulants that negatively affect immune function (AMP, MPH, methylxanthines, pseudoephedrine, etc), you are left with a very short list: tianeptine, agomelatine, modafinil.

These drugs won't permanently 'remodel' your brain, all the receptors will re-regulate after discontinuation within a couple of months. The reason why antidepressants can result in an individual being 'cured' of depression is because the individual makes tangible changes to their life and thought processes while being enabled by the drug, resulting in a sustained change in neurochemistry (exempting neuro-regeneration). If you just sit on your arse while taking these drugs, whatever issues you have will return gradually after you discontinue their use. Try missing a tianeptine dose, the mood elevating effects will wear off rapidly.

I am primarily trying to counter the negative effects of chronic infection on the brain (such as 5-HT2C upregulation in response to cytokines), not treating organically arisen psychiatric disorders as most people are with these drugs. So in my case I fully intend to remain on these drugs until I such time as I am completely recovered from Lyme.

I disagree that I am "wasting" the agomelatine -- at the very least, even if it provided no antidepressant effect, the superior quality sleep it provides is very important, as well as the stimulating effects of its strong MT1 and MT2 agonism on the immune system. I'm depending primarily on tianeptine for the bulk of the antidepressant effect. Tianeptine is the cake, agomelatine is the frosting on top. However, should I decide at some point that it is adding zero antidepressant effect to that of the tianeptine, after sufficient time has passed I would consider discontinuing it and replacing it with melatonin.

I can only imagine the scolding that awaits me when I start using modafinil as well.

Edited by FunkOdyssey, 27 July 2010 - 04:08 AM.

[Animal]

tianeptine is not an inverse agonist of 5-HT2C receptors, I'm not sure why you keep characterizing it this way.

I wasn't claiming it was, maybe my post was a bit unclear, but specifically it is an inverse-agonist of pre-synaptic serotonin receptors. This has a secondary effect on all 5-HT receptors, including 5-HT2C receptors, inducing receptor upregulation.

[Animal]

I haven't kept my regimen updated very well on here, I'll update it in the next couple days along with the rationale for all the changes. Briefly, I've done an insane amount of research in the last few weeks regarding the substantial influence of antidepressant and psychostimulant drugs on the immune system, which is important in my case because I have Lyme. I was forced to drop dexmethylphenidate as a result, leaving escitalopram unbalanced by anything dopaminergic. I briefly toyed with the idea of augmenting it with an agonist (ropinirole) but ultimately decided against it, and went back to tianeptine which I've used before. I'll acknowledge the addition of agomelatine after such a short time on tianeptine is a bit hasty but I have prior experience with both drugs so I'm not flying entirely blind.

What I'm trying to treat: mild depression/dysthmia/anhedonia, mild anxiety (more panic than GAD, tianeptine is already controlling this 100%, escitalopram did as well), inattentive ADHD, shitty libido. Most of this is probably secondary to Lyme but I think there's potential for symptomatic treatment anyway. My antibiotic treatment of Lyme is ongoing and supervised by an LLMD.

If you eliminate all antidepressants that negatively affect libido (SSRI's, SNRI's, TCA's, MAOI's) and/or immune function (NRI's, NaSSAs), and all psychostimulants that negatively affect immune function (AMP, MPH, methylxanthines, pseudoephedrine, etc), you are left with a very short list: tianeptine, agomelatine, modafinil.

I am primarily trying to counter the negative effects of chronic infection on the brain (such as 5-HT2C upregulation in response to cytokines), not treating organically arisen psychiatric disorders as most people are with these drugs. So in my case I fully intend to remain on these drugs until I such time as I am completely recovered from Lyme.

I disagree that I am "wasting" the agomelatine -- at the very least, even if it provided no antidepressant effect, the superior quality sleep it provides is very important, as well as the stimulating effects of its strong MT1 and MT2 agonism on the immune system. I'm depending primarily on tianeptine for the bulk of the antidepressant effect. Tianeptine is the cake, agomelatine is the frosting on top. However, should I decide at some point that it is adding zero antidepressant effect to that of the tianeptine, after sufficient time has passed I would consider discontinuing it and replacing it with melatonin.

I can only imagine the scolding that awaits me when I start using modafinil as well.

I'm not trying to lecture you or scold you, I just think it is unwise to begin taking multiple pharmaceuticals that require chronic dosing at virtually the same time. It will be difficult for you to discriminate between the long term effects of either, or to know whether you would in fact feel better if you were just taking one for an extended period rather then both. Since the MOA of tianeptine is still in conjecture there is the very real possibility that a negative reaction could result over time. Neither of these pharmaceuticals are cheap, I would have thought you'd like to know for definite whether both are necessary.

Modafinil is different in that it only has acute effects so it should be fairly easily to recognise your response.

Part of the reason I responded quite negatively is because I couldn't see your rational for taking them both so soon after you claimed to be enjoying your regime, I assumed (wrongly) that you were one of those people who's constantly trying to maintain a sort of 'high' by throwing together whatever mood enhancers you can get your hands on. There are a few of these kinds of people on the forum.

But since you explained your rational, and I understand that you're primarily trying to counteract the psychological effects of chronic lyme disease, it makes me much more positive about the whole scenario.

I am still extremely interested in the results of this and lets be honest it's an experiment really, so the results may not be what either of us have predicted. Keep us updated please! Could you make a topic specifically for this purpose?

[FunkOdyssey]

I'm not trying to lecture you or scold you, I just think it is unwise to begin taking multiple pharmaceuticals that require chronic dosing at virtually the same time. It will be difficult for you to discriminate between the long term effects of either, or to know whether you would in fact feel better if you were just taking one for an extended period rather then both. Since the MOA of tianeptine is still in conjecture there is the very real possibility that a negative reaction could result over time. Neither of these pharmaceuticals are cheap, I would have thought you'd like to know for definite whether both are necessary.

Modafinil is different in that it only has acute effects so it should be fairly easily to recognise your response.

Part of the reason I responded quite negatively is because I couldn't see your rational for taking them both so soon after you claimed to be enjoying your regime, I assumed (wrongly) that you were one of those people who's constantly trying to maintain a sort of 'high' by throwing together whatever mood enhancers you can get your hands on. There are a few of these kinds of people on the forum.

But since you explained your rational, and I understand that you're primarily trying to counteract the psychological effects of chronic lyme disease, it makes me much more positive about the whole scenario.

I am still extremely interested in the results of this and lets be honest it's an experiment really, so the results may not be what either of us have predicted. Keep us updated please! Could you make a topic specifically for this purpose?

I will post updates in my regimen thread more frequently. Actually though, I think I've already on only my second day encountered an unacceptable agomelatine effect. It seems to have countered the substantial libido boost I was getting from tianeptine alone. Yesterday I chalked that up to poor sleep, but last night I slept very well and drive is still in the shitter.

I don't recall agomelatine having that effect when I used it previously, although it was probably over a year ago. I've been under the impression it could "do no wrong" in that department, however while it seems to be much better than SSRI's its not entirely innocent:

J Psychopharmacol. 2010 Jan;24(1):111-20. Epub 2008 Sep 18.
Better sexual acceptability of agomelatine (25 and 50 mg) compared with paroxetine (20 mg) in healthy male volunteers. An 8-week, placebo-controlled study using the PRSEXDQ-SALSEX scale.

Montejo AL, Prieto N, Terleira A, Matias J, Alonso S, Paniagua G, Naval S, Parra DG, Gabriel C, Mocaër E, Portolés A.

Servicio de Psiquiatría, Hospital Universitario de Salamanca, Salamanca, Spain. amontejo@usal.es
Abstract

Sexual dysfunction (SD) is a common and underestimated effect of antidepressants. Healthy volunteers are the most adequate group to study this adverse event avoiding influence of depression itself. Sexual acceptability of agomelatine (a melatonergic agonist and 5HT(2C) antagonist) paroxetine and placebo by using the Psychotropic-Related Sexual Dysfunction Salamanca Sex Questionnaire (PRSEXDQ-SALSEX) was explored. A total of 92 healthy male volunteers were randomised to agomelatine (25 or 50 mg), paroxetine 20 mg or placebo for 8 weeks. SD, defined as at least one sexual impairment in one of the following PRSEXDQ-SALSEX items (decreased libido, delayed orgasm/ejaculation, anorgasmia/no ejaculation and erectile dysfunction), was evaluated at baseline and after 2, 4 and 8 weeks. At the last post-baseline assessment, SD was significantly lower in each agomelatine group (22.7% on 25 mg and 4.8% on 50 mg) than in the paroxetine group (85.7%; p < 0.0001). In the placebo group, 8.7% of volunteers reported a SD. The percentages of volunteers with moderate or severe SD were 4.5% for agomelatine 25 mg, 4.8% for agomelatine 50 mg, 61.9% for paroxetine 20 mg and 0% in the placebo group (p < or = 0.0001 agomelatine versus paroxetine). There is a much lower risk of having SD with agomelatine than paroxetine in healthy male volunteers, which confirms the better sexual acceptability profile of agomelatine compared with the SSRIs.

PMID: 18801825

I don't think that trial was adequately powered but there are some clear trends. Paroxetine was predictably terrible but at 25mg agomelatine was significantly worse than placebo (25.7% vs 8.7% sexual dysfunction). Interestingly at 50mg agomelatine is superior to placebo. I'm guessing at that dose the positive effects 5-HT2C antagonism begin to take precedence over the negative effects of MT1 and MT2 agonism. However, I can't afford to take 50mg a day, that would be ridiculously expensive (~$125 a month for that drug alone).

So, I think this combination experiment is over, back to tianeptine monotherapy (until my modafinil arrives).

Edited by FunkOdyssey, 27 July 2010 - 02:57 PM.

[Animal]

Damn, I'm on agomelatine at the moment, for just under a month, I haven't noticed any prominent sexual dysfunction at 25mg/day, but I still have difficulty maintaining an erection for an extended period in penetrative sex, which only began occurring after I took Citalopram for months. I have been off the citalopram for about 5 weeks and although my general sexual health has improved immensely since then, it is not back to what it was before the citalopram and I'm wondering if the agomelatine is to blame.

I can't really afford 50mg/month either, although it seems that's when agomelatines positive effects on DA and NE become evident. Boo fucking hoo, i'll stick with the agomelatine for a while, since I hate the triple daily dosing regime of tianeptine. Do you ever notice that the tianeptine has worn off in the morning?

[FunkOdyssey]

I can't really afford 50mg/month either, although it seems that's when agomelatines positive effects on DA and NE become evident. Boo fucking hoo, i'll stick with the agomelatine for a while, since I hate the triple daily dosing regime of tianeptine. Do you ever notice that the tianeptine has worn off in the morning?

Well I do think agomelatine would be exhibiting positive DA and NE related behavioral effects at 25mg, just not enough to overpower the negative sexual effects of the melatonin agonism (which probably max out at 25mg or even lower, whereas 5-HT2C antagonism continues to scale with dose).

There is considerable individual variability in agomelatine metabolism and I bet slower metabolizers are able to reach concentrations at 25mg that are helpful for libido while fast metabolizers are suffering and would need 50mg. This would account for the variety of libido related testimonials I've seen for agomelatine (some good, some bad).

I don't feel much different before/after taking the tianeptine dose in the morning.

[Thorsten3]

I find the drug very stimulating at 25mg and I've mentioned on other forums that this is definitley the best drug I have ever taken. Everyone is different and I am also a big fan of tianeptine - but agomelatine is even better for me.
If anything it is starting to go the other way now. Where as it promoted deep sleep for me in the first week of taking it I am now noticing less consistency with the sleep quality. I am having more broken nights and odd bouts of insomnia because I am finding this drug so stimulating. So I don't agree that it is benign in its effects. It depends on the individual I suppose. I'm 6ft 1 and am very tolerant of most meds/drugs I have tried so I i'm not bullshitting when saying how effective this drug is for me.
I did read an interview on the net from a doctor (can't remember where he was based or the link to the site, but somewhere where they obviously prescribe agomelatine) and he stated that 1/3 of his patients prescribed the drug had a dramatic reaction to it, 1/3 had no reaction to it and became irratated by side effects and the other 1/3 had an average reaction and would tend to loose interest in it. You couldn't really rely on this alone for a full understyanding of agomelatine's effiency but it was worth making note of. So yeah this drug is probably not for everyone.

I've been on it for 12 days by the way. I also take bacopa (1g), fish oil and piracetam (on work days) and there are no contradictions.

Oh and I combined it with tianeptine when I first started agomelatine a couple of weeks back but I found it was too much for me. I definitley agree that it would be better to bed one drug in after you've settled on one for a while. I found it too much at once.

I've enjoyed reading this thread though. Some good information!

Edited by Thorsten, 28 July 2010 - 06:16 PM.

[OneScrewLoose]

I think Animal is confusing the action of tianeptine of lowering agonism of 5HT2c receptors by reducing serotonin levels, calling it reverse agonism, and an actual inverse agonist. And inverse agonist is something that attaches to the receptor and causes the opposite effect an agonist would have. So if an agonist of 5HT2c reduces dopamine levels, an inverse agonist of the receptor would directly increase dopamine (as opposed to increasing it by simply blocking it with an antagonist.

I am still on it, and it's still making me enjoy things more. SInce I am almost sure that Lamictal is a 5HT2a agonist based on personal experiences and interactions with other things I am taking, I am wondering if Lamictal is at all a 5HT2c agonist, because it so well reversed the side-effects I was talking about.

I am currently taking 50mg, and I recently went down to 25mg but noticed a reduction in positive effects so I went back up. I am about to leave Europe though, and am worried that I will still need it, even after the Memantine change. For those who are taking it, please PM me about how you are getting it. I just thought of something and am going to mail someone at alldaychemist to see if there is anyone in India making a generic of it and to see if they can start carrying it.

[FunkOdyssey]

I am currently taking 50mg, and I recently went down to 25mg but noticed a reduction in positive effects so I went back up. I am about to leave Europe though, and am worried that I will still need it, even after the Memantine change. For those who are taking it, please PM me about how you are getting it. I just thought of something and am going to mail someone at alldaychemist to see if there is anyone in India making a generic of it and to see if they can start carrying it.

Agomelatine Psychonauts Group on Google Groups

[John Barleycorn]

There is considerable individual variability in agomelatine metabolism and I bet slower metabolizers are able to reach concentrations at 25mg that are helpful for libido while fast metabolizers are suffering and would need 50mg. This would account for the variety of libido related testimonials I've seen for agomelatine (some good, some bad).

I've just noticed how terrible the bioavailability is. I'm wondering at this point whether the molecule is sufficiently non-polar to absorb sublingually or buccally. 25 mg is no problem as far as volumes go. That might tilt the economics in a more favourable direction. Does the product info say anything about taking it with food?

I'm not turning up much about agomelatine's metabolites or their activity, but as an amide, there is a distinct possibility that it is hydrolysed in the gut when taken orally.

[OneScrewLoose]

Yeah, I am pretty aware of that group, but I was just hoping that I didn't have to dig through the info and that someone could give me a direct link.

[FunkOdyssey]

Yeah, I am pretty aware of that group, but I was just hoping that I didn't have to dig through the info and that someone could give me a direct link.

http://groups.google...ine-psychonauts

[John Barleycorn]

OK, the agomelatine product info suggests that it is poorly water soluble and has no significant metabolites. The experience round the Google group seems to be that the potency of sublingual agomelatine is about 8X that of oral. Putting that in perspective, 6.25 mg (ie, a quarter tab) sublingual is about as much as anyone can take without unpleasant side effects.

[OneScrewLoose]

Yeah, I am pretty aware of that group, but I was just hoping that I didn't have to dig through the info and that someone could give me a direct link.

http://groups.google...ine-psychonauts

I meant to a place to buy it.

[FunkOdyssey]

Yeah, I am pretty aware of that group, but I was just hoping that I didn't have to dig through the info and that someone could give me a direct link.

http://groups.google...ine-psychonauts

I meant to a place to buy it.

I'm slightly irritated. Did you even go there? That's where you buy it, look in the files section.

[John Barleycorn]

I meant to a place to buy it.

Don't overlook unitedpharmacies. They may look dearer, but they accept credit cards. Too bad they won't ship here.

Edited by John Barleycorn, 04 August 2010 - 08:57 AM.

[YoungSchizo]

Finally found a topic on the web about Agomelatine & Stablon combo. (was anxious to try it out!)
Now, I was wondering, Valdoxan has very positive effects on my mood, for 2 days I used 25mg at 12pm and 25mg at 6pm and told my pdoc assistant about this, she said: it might mess up my Melatonine household so keep taking it before going to bed. Is this true?
(Because of what she said I kept taking it before going to bed, the effect of agomelatine on a good night sleep isn't the same as when (3 months ago) I began taking it, I wake up 2 times at night (quite annoying))

What do you guys think/suggest?

And thank you guys for the information about Ago & stablon combo!

[FunkOdyssey]

Finally found a topic on the web about Agomelatine & Stablon combo. (was anxious to try it out!)
Now, I was wondering, Valdoxan has very positive effects on my mood, for 2 days I used 25mg at 12pm and 25mg at 6pm and told my pdoc assistant about this, she said: it might mess up my Melatonine household so keep taking it before going to bed. Is this true?
(Because of what she said I kept taking it before going to bed, the effect of agomelatine on a good night sleep isn't the same as when (3 months ago) I began taking it, I wake up 2 times at night (quite annoying))

What do you guys think/suggest?

And thank you guys for the information about Ago & stablon combo!

It's the 5-ht2c antagonism. It's stimulating. I don't think there's anything you can do except pile on some sedative supplements/drugs at bedtime if you want to keep using it. And yes, you should be taking it at or shortly before bedtime or it will screw up your circadian rhythm.

[YoungSchizo]

Finally found a topic on the web about Agomelatine & Stablon combo. (was anxious to try it out!)
Now, I was wondering, Valdoxan has very positive effects on my mood, for 2 days I used 25mg at 12pm and 25mg at 6pm and told my pdoc assistant about this, she said: it might mess up my Melatonine household so keep taking it before going to bed. Is this true?
(Because of what she said I kept taking it before going to bed, the effect of agomelatine on a good night sleep isn't the same as when (3 months ago) I began taking it, I wake up 2 times at night (quite annoying))

What do you guys think/suggest?

And thank you guys for the information about Ago & stablon combo!

It's the 5-ht2c antagonism. It's stimulating. I don't think there's anything you can do except pile on some sedative supplements/drugs at bedtime if you want to keep using it. And yes, you should be taking it at or shortly before bedtime or it will screw up your circadian rhythm.

What are the harms of a screwed up circadian rhythm? Right now, I'm also on a high dose of Zyprexa (15mg), years ago, this kept me sleeping 12 hours, agomelatine is counteracting this. (I wake up refreshed that's positive).
What kind of supplement/drugs you suggest I should take if Stablon does not recover my sleep rhythm (sleeping 9 hours straight is my goal).

Edited by YoungS, 21 September 2010 - 03:52 PM.

[FunkOdyssey]

Finally found a topic on the web about Agomelatine & Stablon combo. (was anxious to try it out!)
Now, I was wondering, Valdoxan has very positive effects on my mood, for 2 days I used 25mg at 12pm and 25mg at 6pm and told my pdoc assistant about this, she said: it might mess up my Melatonine household so keep taking it before going to bed. Is this true?
(Because of what she said I kept taking it before going to bed, the effect of agomelatine on a good night sleep isn't the same as when (3 months ago) I began taking it, I wake up 2 times at night (quite annoying))

What do you guys think/suggest?

And thank you guys for the information about Ago & stablon combo!

It's the 5-ht2c antagonism. It's stimulating. I don't think there's anything you can do except pile on some sedative supplements/drugs at bedtime if you want to keep using it. And yes, you should be taking it at or shortly before bedtime or it will screw up your circadian rhythm.

What are the harms of a screwed up circadian rhythm? Right now, I'm also on a high dose of Zyprexa (15mg), years ago, this kept me sleeping 12 hours, agomelatine is counteracting this. (I wake up refreshed that's positive).
What kind of supplement/drugs you suggest I should take if Stablon does not recover my sleep rhythm (sleeping 9 hours straight is my goal).

Valerian root, lemon balm, glycine, magnesium are some things you could try. For pharmaceuticals, pregabalin at a low dose at bedtime works well.

[stablemind]

Which countries provide this drug? Is it available anywhere in the US?

[YoungSchizo]

Which countries provide this drug? Is it available anywhere in the US?

(From what I know)
Valdoxan - Brazil, Russia, Ukraine, the EU. Valdoxan is scheduled for FDA approval somewhere in 2012(!)
Stablon - France, Turkey, India, mainly not available in Western countries.

[QuantumTubule]

Hey got a speculation as to mode of action of Agomelatine
Agonising Melatonin receptors causes a increase in acetylserotonin (Acetylserotonin is shown to increase after chronic SSRI use and appears to be causative in the neurogenic and AD effect. Melatonin agonisim and Acetylserotonin concentration are assumed to coupled in that an increase in one will increase another, I only have a vague memory of these processes.

Increased Acetylserotonin increases agonism of TrckB, TrckB is also activated by BDNF and is involved in synaptic vescular& protien trafficing, Agonising TrackB causes a favourable alteration of particular NMDAR, that increases signal transduction and biological viability.

This acts as a antidepressent.

Highlighting that Agomelatine is contraindicated in dementia is important. I can speculate that Agomelatine may increase disease in some pathologies, Agonising Melatonin receptors is expected to cause a decrease in vivo melatonin, through negative feedback. This will cause a decrease in the antioxidative capacity of CerebralSpinalFluid. This will be offset to an unknown extent by increased Acetylserotonin which is also a potent antioxidant. Melatonin/acetyl(5htp) is a special antiox in that it behaves in differing whys to the majority of others, therefore other antiox may not offset this lowered antioxidant status. However TrckB stimulation does decrease oxidative load, and neurogensis offsets neurodegeneration. So no conclusions on the relevancy of ago on antiox, Go through a doc if you could have a neurodegenerative disease.

M

Edited by QuantumTubule, 20 October 2011 - 11:18 AM.

[Omega 3 Snake Oil]

Does anyone know if agomelatine is available in Canada?