Talk:Agomelatine

message: 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 <http://www.emea.eu.int/pdfs/human/opinion/267703062en.pdf>.
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)
thread_title:  European Medicines Agency (EMEA) 

message: "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)
replies: text: 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)
thread_title:  NDDI 

message: 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 http://www.ncbi.nlm.nih.gov/pubmed/20020562?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=1)
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 (talk • contribs) 15:11, 12 January 2010 (UTC)
thread_title:  efficacy 

message: It gives a lot of users a lot of stomachproblems. Definitily not better then an ssri in that case.  —Preceding unsigned comment added by 86.95.68.243 (talk) 10:04, 12 March 2010 (UTC)
thread_title:  gastro intenstinal problems 

message: 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)
thread_title:  sleep 

message: 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)
thread_title:  Failure of Agomelatine in the US 

message: 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)
thread_title:  It is very remarkable that adverse effects are not mentioned 

message: This page seems to copy heavily, word for word, from . Not sure if that's okay or not. C6541 (T↔C) 03:33, 10 September 2012 (UTC)
thread_title:  Copies heavily from product info 

message: ... 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 http://pdsp.med.unc.edu/pdsp.php?knowID=&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testDDRadio=testDDRadio&testLigandDD=3873&testLigand=&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query  — Preceding unsigned comment added by 178.235.75.252 (talk) 23:40, 22 July 2013 (UTC)
thread_title: MECHANIZM OF ACTION

message: 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:  http://m.bjp.rcpsych.org/content/203/3/A11.full  
See also:  http://m.bjp.rcpsych.org/content/203/3/179.short  
--Hordaland (talk) 05:54, 17 September 2013 (UTC)
thread_title:  Sept. 2013 review 

message: 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)
thread_title:  Error in "3D" representation? 

message: 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 - http://www.ncbi.nlm.nih.gov/pubmed/12750432 . 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 - http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=1325056Basuraeuropea (talk) 21:03, 20 September 2014 (UTC)
thread_title:  5-HT2B Antagonism 

message: All cause discontinuation rates do not differ per "In active comparator trials 377/2215 (17%) discontinued agomelatine and 392/2067 (19%) comparator antidepressants (fig 12​12).). Patients were no more likely to discontinue agomelatine than... comparator antidepressant (0.90, 0.76 to 1.07; fig 12​12)."
Doc James (talk · contribs · email) 11:37, 15 January 2020 (UTC)
thread_title: Discontinuation rates

message: "Common side effects (may affect up to 1 in 10 people): dizziness, sleepiness (somnolence), difficulty in sleeping (insomnia), feeling sick (nausea), diarrhoea, constipation, abdominal pain, back pain, tiredness, anxiety, abnormal dreams, increased levels of liver enzymes in your blood, vomiting, weight increased." Page 28  
BNF 76 lists "Common or very common Abdominal pain . anxiety . back pain . constipation . diarrhoea . dizziness . drowsiness . fatigue . headaches . nausea . sleep disorders . vomiting . weight changes" Doc James (talk · contribs · email) 11:39, 15 January 2020 (UTC)
thread_title: Side effects

message: US clinical trials are back on as of 2021. there seem to be multiple listings on clinicaltrials.gov, with only capitalization differences between them?  i'm not confident enough to edit wikipedia anyways but i thought i'd drop this here for somebody who is.
https://clinicaltrials.gov/ct2/show/NCT05118750
https://clinicaltrials.gov/ct2/show/NCT05157945 BarrowSys (talk) 20:38, 17 September 2022 (UTC)
thread_title:  2021 US Clinical Trials