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European Medicines Agency (EMEA)[edit]

On 27 July 2006 the Committe for Medical Products for Human Use (CHMP) of the European Medicines Agency (EMEA) recommended a refusal of the marketing authorisation of Valdoxan/Thymanax. The major concern was that efficacy had not been sufficiently shown. The CHMP had no special concerns about the side effects. See <>. I've removed the POV tag following the canges made by my colleague Phan Nyom. The recent changes have been adapted from the European SPC. This article is now more objective.PhanLongon 22 September 2010 —Preceding undated comment added 14:05, 22 September 2010 (UTC).

Added previous comment on the main article because it states very important informations about this drug. Artkin 08:54, 2 April 2007 (UTC)

Structural similarity to melatonin[edit]

Sorry, but this compound does not have a structural similarity to melatonin. It has two benzene rings bound together (making a naphthalene) whereas melatonin and all tryptamines have a pyrrole group (making an indole). That changes the whole compound.

I'm changing this, if someone feels otherwise you can change it back and leave a note here as to why this undo is justified. —Preceding unsigned comment added by (talk) 07:32, 20 May 2009 (UTC)

I agree with you and I've removed this part. —Preceding unsigned comment added by PhanNyom (talkcontribs) 13:23, 22 September 2010 (UTC)

There clearly is much similarity in the structures of agomelatine and melatonin. Naphthalene and indole are indeed different, but they do have similarities. The rest of the molecule is identical. Read the article that I cited: its title is "a Potent Melatonin Analog" and states "This interest prompted us to develop new melatonin receptor ligands and led to the synthesis of a naphthalenic bioisostere".
If you have a suitable reference to peer-reviewed scientific literature that states agomelatine and melatonin are not structurally similar, then post it here and we can discuss. Otherwise my text can stay.
Ben (talk) 14:07, 22 September 2010 (UTC)


"Agomelatine is known as a norepinephrine dopamine disinhibitor (NDDI) because of its 5HT2C antagonistic properties of inhibiting 5HT, thereby disinhibiting DA and NE release" --Stephen M. Stahl, MD, PhD author of "Essential Psychopharmacology". I wish the abstract of the source I gave would mention it, but it doesn't. A quick googling of the statement should prove any skeptic. --WhereIsMarty (talk) 08:56, 28 August 2009 (UTC)

I googled it and didn't find anywhere else saying that agomelatine is known as a norepinephrine dopamine disinhibitor. —Preceding unsigned comment added by (talk)

I searched "norepinephrine dopamine disinhibitor" on Google Scholar, and found Stahl's 2007 article. Haven't read it yet, but I have full access to it. Mutual monarch (talk) 20:28, 4 September 2009 (UTC)

Misleading information. I have changed this section according to the official European Medicine Agency summary of product characteristics.


I'm new to editing on wiki, so i'm starting a discussion first.

In my opinion, it has not at all been shown that agomelatine is efficious, let alone "comparable to paroxetine and sertraline". The source for this statement is a very short article about a presentation, not a RCT published in a (peer-reviewed) journal. I think it is much to early to classify agomelatine as a effective & safe antidepressant. True: probably less sexual side effects & beneficial effect on disturbed sleeping patterns. Also true: the potential for serious adverse hepatic effects.

A bit more about evidence: from Prescrire Int. 2009 Dec;18(104):241-5. (abstract available via

Agomelatine: new drug. Adverse effects and no proven efficacy.

(1) When an antidepressant is considered a necessary addition to psychological support in treating patients with depression, the first-line drug is a tricyclic such as clomipramine or a selective serotonin reuptake inhibitor (SSRI) such as paroxetine; (2) Agomelatine, a melatonin receptor agonist, is approved in the European Union for the treatment of depression; (3) Available evaluation does not include any clinical trials designed to compare the efficacy of agomelatine with that of a tricyclic or a selective serotonin reuptake inhibitor. Most data come from 7 placebo-controlled trials; (4) Agomelatine (25 mg/day) was statistically more effective (on a rating scale) than placebo in only 3 of these 7 trials. The clinical relevance of the score improvements is questionable. No data are available on the cure rate or on suicide prevention; (5) In one trial, increasing the daily dose from 25 mg to 50 mg provided no supplementary benefit; (6) A trial in 367 patients failed to show that agomelatine was any more effective than placebo in preventing new depressive episodes (29% after one year). In another trial including 339 patients, the relapse rate was statistically lower after 6 months on agomelatine (20.6%) than on placebo (41.4%); (7) Very high doeses of agomelatine are oncogenic in animals. The risk in humans is not known. Dizziness, gastrointestinal and cutaneous disorders have been observed. Agomelatine is probably hepatotoxic; (8) In summary, agomelatine has unproven efficacy and poorly documented adverse effects. It is better to continue to use older antidepressants such as tricyclics or serotonin reuptake inhibitors.

comments anyone? —Preceding unsigned comment added by Abcdefgijs (talkcontribs) 15:11, 12 January 2010 (UTC)

gastro intenstinal problems[edit]

It gives a lot of users a lot of stomachproblems. Definitily not better then an ssri in that case. —Preceding unsigned comment added by (talk) 10:04, 12 March 2010 (UTC)

major bias[edit]

Based on the peer-reviewed literature I've read, this article seems to be very biased against agomelatine (eg. if I'm not mistaken repeated placebo-controlled trials with multiple SSRIs failed to reach stat significance). I will try to update when I get a chance, but any other article input to make this more objective would be much appreciated.--Xris0 (talk) 02:54, 29 March 2010 (UTC)

I don't see any bias against agomelatine here, instead there may be some pro-bias, since important facts are missing or obscured:
1.) The EMEA (now called EMA)/CHMP deemed[1] agomelatine to be probably less efficacious than other currently available antidepressants. This was based on the fact, that agomelatine failed in 3 out of 4 active-controlled trials, while the (SSRI) comparators failed in 2 (i.e., the normal rate for newer antidepressants, or 50%). In one trial, fluoxetine was significantly more effective than placebo while agomelatine was not. On the other hand, the mean difference on the HAMILTON DRS across all trials was only 1,5 points in favour of agomelatine, thus the EMEA called the clinical significance of this difference doubtful resp. marginal.
2.) "The CHMP had no special concerns about the side effects" is an outdated citation from the 2006 CHMP Refusal AR. In the 2008/2009 EPAR, there is clear documentation of agomelatine's liver toxicity, with dose-dependent risk for liver enzyme elevations (a common side-effect) and several cases of severe liver injury. That's why they imposed liver function tests as a regular safety measure, a major obstacle for a weak antidepressant.
2 of the 3 US studies are now published (the second soon to be listed in MedLine), and as in the EU trials, there was no dose-response relationship - 50mg not more effective than 25mg. But in the newer trials, the liver enzyme elevations were even more common than in Europe (3,0 and 4,5%), indicating either that US livers are more susceptible to agomelatine - or the Europeans did not really want to see the problem.
Unfortunately, the peer-reviewed literature on agomelatine is meager, the developing firm choose not to publish many of the equally important negative results, intead they flooded journals worldwide with advertorials[2][3]. Sincerely --Philipp-R.Schulz (talk) 11:50, 10 April 2010 (UTC)

It doesn't seem to me that they are employees.shoi (talk) 13:17, 10 September 2011 (UTC)SteveH

Agomelatine isn't actually more harmful to the liver than most SSRI's. (talk) 01:51, 29 June 2010 (UTC)


In the lead paragraph we currently have the rather vague statement, "Agomelatine may also have positive effects on sleep". Does this mean Agomelatine might regulate all sleep disorders (including hypersomnia)? Or does it mean it reduces insomnia? Thanks. -- TyrS  chatties  04:16, 3 February 2011 (UTC)

Failure of Agomelatine in the US[edit]

If you cannot access the Scrip Article, go for the 3rd quarter release by Novartis.

"Amerika, Du hast es besser", BR --Philipp-R.Schulz (talk) 14:26, 30 October 2011 (UTC)

It is very remarkable that adverse effects are not mentioned[edit]

There must be something wrong here. Well known adverse effects are not mentioned at all. I would be glad if each contributor explained what has happened here. Nopedia (talk) 16:03, 4 September 2012 (UTC)

Copies heavily from product info[edit]

This page seems to copy heavily, word for word, from [1]. Not sure if that's okay or not. C6541 (TC) 03:33, 10 September 2012 (UTC)


... 5-HT2C antagonist (IC50=270nM; pKi=6.15±0.04). <-What is pKi (I know what is Ki but pKi?)
and should there be nM unit?

Ki for agomelatine for 5ht2c = 707nm, so it is very, very weak antaginizm — Preceding unsigned comment added by (talk) 23:40, 22 July 2013 (UTC)

Sept. 2013 review[edit]

New review - possibly of interest for this article:

Markus Koesters, Giuseppe Guaiana, Andrea Cipriani, Thomas Becker, and Corrado Barbui Agomelatine efficacy and acceptability revisited: systematic review and meta-analysis of published and unpublished randomised trials BJP September 2013 203:179-187; doi:10.1192/bjp.bp.112.120196

About this paper: "...conflicting results between the unpublished and published studies, with none of the negative studies having been published." and "...the European Medicines Agency should aim to have a more robust procedure for evaluating novel drugs,[...] insisting on submission of all available drug studies, rather than relying on a selection of relevant studies provided by the manufacturer." These comments are from:

See also:

--Hordaland (talk) 05:54, 17 September 2013 (UTC)

Error in "3D" representation?[edit]

I notice that the GIF animation doesn't correspond to the structural formula. In the animation, the nitrogen is missing a hydrogen, and the nearby oxygen is shown as hydroxyl rather than amide. --Cedderstk 10:23, 27 July 2014 (UTC)

5-HT2B Antagonism[edit]

I know the serotonergic properties of the drug are widely accepted as being limited to 5-HT2C receptor-site antagonism, although I found whilst looking through articles on pubmed a mentioning of the drug's antagonistic affinity for 5-HT2B which seems to be clinically significant. The link to the article follows - . Do all of you armchair psychopharmacologists think that this should be worth mentioning under the pharmacology section of the article or not? If so, then the drug should be listed as an antagonist on the 5-HT2B Wikipedia page as well. If not, why?

Should there be no response and/or no rejection of the addition of the drug as an antagonist at said site unmentioned, I'll amend the article appropriately after a period of time to allow for review.

edit: see this as well - (talk) 21:03, 20 September 2014 (UTC)