Template talk:Antidepressants

American/FDA bias and drug inclusion/exclusion criteria: Refactoring Proposition W1

by WhereIsMarty (talk) 04:54, 30 August 2009 (UTC) updated on

Lets remember ourselves that this is en.wiki.x.io, not us.wiki.x.io or euro.wiki.x.io: This classification, like everything else on wikipedia, should keep its international character. In no way should a drug be excluded on the basis of not having been approved by a specific governmental organisation; FDA, EMEA, Health Canada and such aren't authoritative on which drugs are antidepressants or not. A lot of their approval process considerations aren't related to the EFFECT of the drug in term of antidepressants quality. As example, a drug could be judged not applicable because it didn't outperformed already established/marketed drugs! This doesn't mean the drug has no antidepressant properties and so the sole authority on the classification of what is antidepressant or not is : Science.

With that in mind, drugs classified in this template should have been the one shown to possess antidepressant QUALITIES and so the one which could be backed as such with credible scientific sources. The fact is that is hasn't been classified that way because as of now, WHAT is it that this template classify has never been clearly stated:

• MOLECULES possessing antidepressant properties?
  • Scientifically demonstrated only?
  • Including anecdotal reports and popular consensus? (Not encyclopedia worthy)
• MEDICINES used as antidepressant?
  • Approved by at least one medical authoritative organisation?
  • Including known off-label use?
  • Including known self-medication?
  • Including so called natural/nutritional supplements?
    • With scientific backing or not?

With so many possible criterion combination, there's no way we can work together efficiently toward an elegant and rigorous version of this classification without defining what are the definitive set of criterion. As of August 2009, the state of the template indicate that we have drugs included for ANY of these criteria. Yet, nobody is happy.

Ideally, we should have separate templates for:

1. "Antidepressant Substances": MOLECULES WHICH SCIENCE KNOWS IS ABLE TO UPLIFT MOOD,which would include every, science backed, antidepressant qualities possessing substances. That includes not only medicines, designer drugs, drugs in development (having succeed at least beyond phase 1) but also herbs/supplements or anything else having credible scientific backing. This should be the superset of the other class, except for a possible "Folk Antidepressants Substances".
2. "Medical Antidepressant Drugs": MOLECULES WHICH MEDICINE USES TO UPLIFT PATIENTS MOOD which would include only drugs that can be demonstrated to be used in medicine somewhere in the world and backed by science (and so a subset of "Antidepressant Substances"). Because of the way medicine decides which drugs are to be used differs from a country to another and because doctors largely override the prescribed uses of the drug (off-labeling), those drugs classified in this category wouldn't need to be approved by any governmental agency of any countries. It is to the individual articles to let the reader knowns if it's approved for that use or not and by who as those informations are political in nature, not uniform internationally and so difficult to classify in that way: in every countries, everywhere and in every ages drugs which were and are used in medicine were and are because it was believe or shown to have an MEDICINAL EFFECT. This is what's giving us a class/category, the effect! Not the governmental prescription/control of the use of those drugs or the even the safety. The subset "Medical Antidepressant Drugs Approved by at Least One Country" could definitively be another category, but a very specialized one considering the logical axis of classification.
3. "Folk Antidepressant Substances": which could include any substances which has been proposed to be popularly known to be antidepressants. This is the set for everything that hasn't been backed scientifically and including the medically used one not backed by science. (Homeopathy and others in some countries)

I propose the following, which I ask you to vote on in the "Poll: Classification Refactoring Proposition W1" in the form of "YES: reason" or "NO: argument, counter proposition":

1. To keep THIS (here) template as the superset (#1), that is the "Antidepressant Drugs" backed scientifically. Would change is name to "Antidepressant Drugs" since drugs aren't the only type of antidepressants: i.e.: ECT, Light Therapy and many more things has been shown by science to be antidepressants. Drugs are just one kind of antidepressant therapy: the psychopharmacological one.
2. To migrate the substances NOT backed or at least well backed (at least 2 sources; peer reviewing principles) to a new "Folk Antidepressants" template. We could replace Folk by Popular, Anecdotal, Proposed, Alternative or else.
3. To copy the substances which are backed by science and used in medicine somewhere in the world, BUT NOT necessarily approved by any countries government, in a new "Medicinal Antidepressant Drugs" template.
4. To enforce respective classification criterion in those 3 templates base on those simple rules:
   1. Which isn't backed by science -> ONLY IN Folk Antidepressant Substances
   2. Which is backed by science -> Antidepressants Drugs (here)
   3. Which is backed by science and used in medicine -> Medicine Antidepressant Drugs AND Antidepressants Drugs.

In November 2009, I'll compute the votes and update this post to reflect the results so as to communicate the will of the majority. --WhereIsMarty (talk) 04:54, 30 August 2009 (UTC)

--- Comments ? Discussion ? Epic Flaming ? --->

Poll: Classification Refactoring Proposition W1

Yes: My reasons can be read in the "American/FDA bias and drug inclusion/exclusion criteria: Refactoring Proposition W1" section. --WhereIsMarty (talk) 04:54, 30 August 2009 (UTC)

Suggestions for refactoring of template=

How about breaking this template up into smaller templates? Essentially, have an Antidepressants template that lists the categories (SSRI, SNRI, DARI, MAOI, etc), and an Antidepressant:XXX template for each of the categories, listing the drugs themselves?

That should limit the confusion, and keep the individual templates more manageable, as well as limiting the need for any controversy about what should be included.

As an example, the escitalopram article would have the Antidepressants/SSRI template, as well as the Antidepressants template, on it, giving the user one box with a list of the types of antidepressants covered on WP, and another box with a list of SSRIs. Zuiram 03:30, 30 October 2006 (UTC)

Archiving

Should we perhaps archive some of the stale material here? The talk page is getting excessively long. Zuiram 03:30, 30 October 2006 (UTC)

Nesting

Nesting templates is reallly bad for server resources and should be avoided at all costs. Is there any way contributors to this article can fix this? gren グレン 17:00, 27 August 2005 (UTC)

Ugghhh - that's one ugly template. The nesting just makes it worse. Anyone care to tidy it up ? Megapixie 06:45, 22 December 2005 (UTC)

I have unnested the templates. --Arcadian 15:12, 23 December 2005 (UTC)

Editing of categories

The only medicines that should be included in this template are those specifically approved for depression, by the FDA or likewise any other drug-monitoring body. If we open templates to include the off-label uses of other medicines, there would be a rapid influx of virtually any drug, with only a single study or source as evidence of efficacy. --Prisonnet 18:34, 6 October 2006 (UTC)

The FDA is not a global authority in this regard.

If you limit this template to those drugs that have MDD as a specific indication, rather than relying on what is actual clinical practice, you will exclude a large number of drugs used for treatment refractory depression.

If this template aims to catalog FDA approvals, it should be renamed to reflect this. If it aims to be an index to the drugs currently being used and routinely showing efficacy in the treatment of depression, it should include several categories that are not currently approved.

A vote would be good here, or at least some kind of policy decision about what the template should reflect. Zuiram 03:24, 30 October 2006 (UTC)

Whoever made lots of deletions etc.. Please either revert the deletions, and move modafinil back to CNS stimulants (it is not simply a DARI, its affinity for NE is about 3 times greater than its affinity for DA), or remove the following items from the template, for consistency:

Harmaline (herb), Iproniazid (recalled), Amineptine (schedule 2), Phenmetrazine (not indicated), Vanoxerine (not generally available yet), Modafinil (not indicated), Atomoxetine (not indicated), Reboxetine (not approved by FDA), Alaproclate (discontinued), Etoperidone (discontinued), Zimelidine (banned worldwide), Maprotiline (recorded in two places), Tianeptine (not approved by FDA), Nefazodone (discontinued).

I'd prefer the more comprehensive list, but the shortened one would be less "confusing", and more in line with FDA regulations.

Zuiram 04:01, 30 October 2006 (UTC)

I didn't say it should be restricted to the FDA, I said "by the FDA or likewise any other drug-monitoring body," which is a big difference. --130.88.188.88 18:20, 6 November 2006 (UTC)

On a side note, nowhere on Nomifensine's page is it mentioned that it is a multiple-uptake inhibitor, even though it is categorized as such. --Prisonnet 18:34, 6 October 2006 (UTC)

Then nomifensine is an incomplete article. The literature clearly supports its action as a triple reuptake inhibitor, with fairly balanced affinity. Zuiram 03:24, 30 October 2006 (UTC)

I agree that only drugs specifically approved for depression should be used on this template otherwise the template would just get cluttered up and become confusing for people. --Benjaminevans82 18:57, 6 October 2006 (UTC)

If you include all the drugs specifically approved approved (sic) for depression, you will get an extremely cluttered-up and confusing template anyway. And the problem will only grow as more drugs are released onto the market.

I suggested that we try to find a different way to organize the template to make it easier to understand, though I'm not sure what that would be.

This is a confusing field for the layperson. I've read thousands of papers on this, and I am still not extensively familiar with all the drugs out there. Zuiram 03:24, 30 October 2006 (UTC)

Leading a research on some effects(or absence of effects) with antidepressants, I compiled have a list that I took from a APA database, I will admit that it is absurdley long and that some have ben discontinued or replaced BUT some of them are still produced on a as-needed basis. To provide a comprhensive list we should include them ALL but putting effect dates (ex. Isocarboxazid(1958-1994)) would be usefull. We also have to keep in mind that some discontinued products can still be in use in other countries, especialy since some chemical compositions might no longer be protected under copywright laws. – — … ° ≈ ≠ ± − × ÷ ← → · § Julien (big supprise) name: Julienrl 04:42, 19 January 2007 (UTC)

Zuiram here, not logged in. A comprehensive list will be of no value as a template. Consider such names as TV3326, GBR12909, etc. And adding dates will also be bloating the template excessively. These things belong in a seperate article ala overview of antidepressants.

Also, I'm actually in an "other" country; local practices vary a lot by region, true, but the broad lines are pretty universal. Selecting something to go by here is a matter of deciding what the template is here for.

Personally, I'm more in favour of a two-level template system. Have one template for the types of antidepressant, and one subtemplate for each type. Hence, when you go to the Bupropion page (oddly enough present on the current template as a NARI, which is wrong, as Wellbutrin, which is contrary to policy), you will see one template listing classes (SSRI, TCA, MAOI, SRE, SNRI, NARI, DRI, etc), and a subtemplate for norepinephrine-dopamine reuptake inhibitors (or whatever it eventually gets classified as here).

Please reply to my [User_talk:Zuiram|talk page], as I don't go to this page very often, having pretty much given up trying to improve its quality until I have the energy to do all the work myself. Zuiram 02:52, 28 January 2007 (UTC)

Julien agian: I too am from an "other" country, it is why I insited on puting that comment, the FDA does not regulate what drugs are used in any country other then the US, some people seem bent on the idea of removing non FDA aproved medication, and it is absurd. I do agree on a 2 dimention table, but I think that adding more sub categories would not make it more complicated, simply a bit longer to read.

Regarding CNS stimulants (reply to Davidruben)

CNS stimulants are used clinically in treatment refractory depression. In fact, it is most frequently used as an adjunct to other medicines. For example, despite "common sense" labelling to the contrary, it actually occurs that when people have reached the maximum dose of Tranylcypromine, without adequate response, the doctors will augment it with Dexedrine.

I've been treated with about half or so of these categories, and some that are not present here, as well as having read about 70.000 pages of research on pharmacological treatment of depression, particularly treatment refractory depression comorbid to ADHD and autism-spectrum disorders.

The field is too complex to be accurately represented by this template in any way, but I'm at a bit of a loss as to where the line should be drawn between accuracy and usefulness. The articles themselves tend not to be overly accurate, nor overly useful, but I doubt that is a good standard to emulate. I'd like to rewrite a few dozen psychopharmaca-articles, but that'd require more sourcing/citing work than I'm prepared to invest right now (I've got most the fulltext papers lying around, but it's hell to dig them all up).

In any case, removing the CNS stimulant category is decreasing the factual content of the template. You can reduce it to dexedrine, desoxyn, PEA and ritalin, though, as these are the only stimulants that are "widely" used. I'd not be inclined to revert a remove of desoxyn (a better choice than dexedrine for this use, but not very "in" at the moment) and ritalin (as combinations are the general case, the drugs that have been around the longest are preferred as they have been studied more extensively).

Zuiram 13:07, 25 September 2006 (UTC)

St. John's Wort

It is not appropriate to place St. John's Wort under alternative medicine. While the alternative people sometimes use it, they generally turn to more esoteric approaches nowadays (proper herbalism is a fairly comprehensive study that IME few alternative practicioners have the inclination to master).

St. John's Wort has been extensively studied, particularly in Germany. Studies regarding efficacy in depression have been about as conclusive as the ones for the prescription drug buspar in anxiety, which is to say that the drug company-sponsored trials conclude one thing, while the independent research concludes another thing. In this case, the independent research indicates a moderate efficacy with a tolerable side effect profile for those not taking other drugs at the same time.

The mechanism of action is presumed to be primarily due to hypericin and hyperforin. From the articles, hypericin acts as an antibiotic and kinase inhibitor. One must also assume the article means to say that it might be a dopamine beta-hydroxylase inhibitor, which would decrease dopamine catabolism at the expense of reduced norepinephrine synthesis. Hyperforin apparently inhibits reuptake of 5HT, NE, DA, GABA and glutamate, as well as inducing CYP3A4 with potential downstream effects on testosterone turnover.

Not mentioned in the articles, one of these (can't recall which right now) has been shown to exhibit weak MAOI-properties.

To sum up, this drug definitely does something neurochemical, definitely classifies as a drug (and is even available in refined form with standardized amounts of the active ingredients, from pharmaceutical companies), and is prescribed by traditionally trained psychiatric professionals. To list it as "alternative" trivializes the potential risks associated with its use, as well as the potential benefits.

Its extremely wide profile makes it difficult to classify, though. Perhaps we should move that and some of the other categories, such as SRE, to this category? Otherwise, I'd say it belongs under "monoamine reuptake inhibitors", or something of the sort, for simplification.

Zuiram 13:07, 25 September 2006 (UTC)

I agree St John Wort is hard to classify. I do feel however that it should be included in the template as they is strong evidence that it is effective for mild to moderate depression. --Benjaminevans82 19:01, 6 October 2006 (UTC)

How about a "Miscellaneous" or "Other" category? Classifying it as "alternative medicine" is rather POV, and deleting it is vandalism IMHO (removal of useful content). Zuiram 03:26, 30 October 2006 (UTC)

St Johns Wort is extremely hard to classify, but at least the category "alternative medicine" conveys to the reader that it is not a prescription drug, but it is effective in treating mild to moderate depression. I can not think of a better category for it and I do really think that it should be included in the template. Does any one else have any thoughts on this? Benjaminevans82 01:03, 2 November 2006 (UTC)

Anyone who makes any decisions about a drug based on its inclusion in a wikipedia template without even reading the article is not likely to have the .. faculties .. to pick up that subtle nuance ;)

Leave it to the St Johns Wort article itself to convey the details. The template is not an article, it is an index to the articles.

Also, In some areas, St Johns Wort is a prescription drug, and synthetic hypericin and/or hyperforin may be prescription in other areas. German doctors prescribe it for depression. Harmaline (herbal) and Amineptine (banned) are not prescribed drugs.

Digoxin is a prescription drug, despite being primarily produced by extraction from foxglove.

If this list is prescription antidepressants, the template name and title should reflect this. If it is just "antidepressants", then prescription should not be a criterion for inclusion/exclusion. You could of course just make an "over-the-counter" category, but I still think "other", "miscellaneous", or some such would be better.

We seem to need a consensus on what constitutes an antidepressant (or what to rename the template to if it is concerned with other criteria), and what the organization of the list should be (mechanism of action, efficacy, prescription/non-prescription, etc.), since I appear to be the only one to consider it self-evident that an "antidepressants" template which has entries listed by (roughly) their assumed main mechanism of action, that this template should list drugs that have shown antidepressant efficacy in studies, organized only by their mechanism of action, not their prescription status and/or legality in any particular country.

Zuiram 19:03, 4 November 2006 (UTC)

The key workd in Zuriam's comment is "particular", we should not limit it to a single country but I do think that the legality aspect should come in play. If it is legaly an antidepressant in your country, then it has its place on the table, as long as it has an article related to it. If by some odd fluke, a product is an antidepresant in a single country but nowhere else in the world, then let that article state it.

Julienrl 18:14, March 30th 2007

Why I repositioned viloxazine and venlafaxine within the template.

I'd been wanting to do it for some time. The unnesting of the templates made it easier. Anyway, I saw that fluoxetine and atomoxetine were both bicyclic compounds and are classified purely on the basis of chemical structure, so why the others (it was my idea, and I don't remember why I did it with viloxazine anymore).--Rmky87 10:58, 6 January 2006 (UTC)

Neither fluoxetine, nor atomoxetine are bicyclic. Polycyclism isn't about overall number of rings in structure, but about the number of rings fused. This is a common misperception in many Wikipedia articles regarding psychopharmaceuticals.--84.163.110.20 (talk) 17:05, 15 April 2008 (UTC)

Accuracy of the template, and the articles for that matter.

Please consult the PubMed database; most articles I have seen on antidepressants have significant factual inaccuracies. I try to make some rough corrections when I see them, but the meta-bits about how the articles are organized, I'll let someone else debate and edit; there are many axis along which to classify these pages. I'll try to offer some help with getting the current table right, though. Here are some corrections off the top of my head (it's late, so doublecheck the sources):

SNRIs: Desipramine is, as the article states, a tricyclic antidepressant (TCA), not an SNRI.

Mood stabilizers: Several of these are actually used in unipolar affective disorders, not just bipolar ones. Their omission is significant, and I'm not convinced the distinction between antidepressants and mood stabilizers is right for such a template.

Opiates: This class has recognized antidepressant effects, though legislation generally prohibits prescription. Buprenorphine shows significant promise, especially in combination with tranylcypromine.

NARIs: Omits adrafinil, which is typically placed in this category.

DARIs: Nomifensine is a triple reuptake inhibitor, with potent dopamine and norepinephrine reuptake inhibiting effects, and a mild serotonin reuptake inhibiting effect. It is properly classified as a "triple reuptake inhibitor" (not to be confused with TCAs), "multiple reuptake inhibitor" or "monoamine reuptake inhibitor". The article stated that its admitted abuse potential was the reason for its withdrawal; this is conjecture, and the official reason for its withdrawal was rare cases of a serious blood disorder resulting from its use.

DARIs: Methylphenidate acts on both NE and DA, and its mechanism is not reuptake inhibition. It is properly classified as a CNS stimulant. Please note that amphetamines, PEA and other stimulants are often used in treatment refractory depression; more so than methylphenidate. The article appears vandalized, or at least NPOV'd.

MAOIs: Tranylcypromine forms a metabolite (para-hydroxy-tranylcypromine) which acts as a triple reuptake inhibitor (5-HT, NE, DA) even at low doses. At higher doses, as MAO-inhibition reaches the clinically effective threshold of about 80% (IIRC, about 1.5mg/kg/day), the combined effect is significant MAO inhibition and significant triple reuptake inhibition.

MAOIs: Phenelzine is an inhibitor of GABA-transaminase and glutamic acid decarboxylase, and forms a metabolite which has MAO-inhibiting properties. This is assumed to be why it is popular and effective in the treatment of anxiety.

Finally, I'd point out that it might be more useful to make a matrix of signal substances and enzymes vs drug, and showing the relative potencies of action. For example, reboxetine has a Ki value for NE alpha-2A of >10000nM/L, making it about 5 orders of magnitude more potent in this regard than most antidepressants. The Ki database could be used for this.

--212.169.96.218 00:43, 7 August 2006 (UTC)

The above comment was me, prior to getting my own account. I have now tried to improve the accuracy and completeness, but some of these drugs are hard to classify correctly, so I've tried to be functional about it. Since this is a template, there is no place to put the sources, so if anyone is unsure whether the edits are correct, just ask, and I'll provide links.

The rationale for the edits are as follows:

* Desipramine is properly a tricyclic compound, and not just due to the chemical structure. It does not display the selectivity profile that would qualify it as an SNRI, as its affinity for the major monoamine transmitters is fairly well-balanced. Furthermore, it has significant affinity for e.g. histamine, ACh, etc., which puts it squarely in the TCA ballpark with regards to receptor profiles.

* Buprenorphine is the most potent and selective kappa-antagonist that is currently available; this mechanism of action has been shown to have antidepressant properties. It also has partial mu-agonist properties, also shown to have antidepressant properties, although I am unsure which other opiates might be successfully used in the treatment of depression, and I have therefore emphasised the kappa-antagonist property to avoid opening that particular can of worms.

* Adrafinil, modafinil and nuvigil might more properly be classified as CNS stimulants, but their therapeutic use is generally related to their norepinephrine-dopamine activity, not the H3, NMDA, etc. activity, according to some sources. Feel free to move them.

* Nomifensine is a triple/multiple/monoamine (pick one, there are few agents in this category, so there isn't a standard term just yet) reuptake inhibitor, and should not be mistaken for a DRI. That is a potentially dangerous misclassification.

* Methylphenidate and amphetamine do not rely on reuptake inhibition, and their profile is not limited to DA (in fact, equivalent Ki is about 3-4,000nmol/L for both NE and DA, and there is also some 5HT activity). Properly, they are classified by their result, which is CNS stimulation. Typically, dexedrine is the preferred amphetamine for antidepressant use.

* Phenylethylamine is an important CNS stimulant, although rarely used; as manufacturers cannot patent it, there is little interest in productifying it. Plus, large quantities are needed if not taken with a MAOI.

* Tranylcypromine was copied to the multiple reuptake inhibition category, as one of its metabolites, thought to contribute significantly to its antidepressant action, has this as its mechanism.

I left out some editing that should probably be done, as we really should find a better classification system, such as the drug vs mechanism of action / receptor profile matrix. Thoughts?

Zuiram 04:27, 9 September 2006 (UTC)

Mirtazapine

Mirtazapine is classified only as a Noradrenergic and specific serotonergic antidepressant in the template, should we add it to the tetracyclic group in duplication? Ill be bold.

Phenmetrazine

Should really phenmetrazine be included in this template? I know Amphetamine has been used as an antidepressive in the past, but to my knowledge phenmetrazine has only been used as an anorexic. (Although I'm sure it would function in that role, to some extent.) 213.67.210.135 15:22, 28 August 2007 (UTC)

I agree that it would probably be better if it were removed from the template. --Arcadian 16:13, 28 August 2007 (UTC)

Cleaner setup

There needs to be a better setup, mostly dealing with the TCA/Tetra, as well as the N RI's, and the A RI's current configuration and setup, it's just a wee tad bit confusing; considering that now all of those medications do both. —Preceding unsigned comment added by 75.10.127.178 (talk) 05:13, 24 October 2007 (UTC)

To-Do: request to categorize MAOI into MAO-A inhibitors and MAO-B Inhibitors

I request splitting MAOI because it's hard to keep track of which drugs are which, plus considering the very different actions and effects of A and B inhibitors, it makes sense to do so. Someone who comes across an article with this template will be intrigued with examining the differences. I'm not changing it myself because I don't understand if RIMAs are... um... MAO-A Inhibitors, MAO-B Inhibitors, both, either, or something in themselves. --geekyßroad^{. meow?} 03:27, 11 December 2007 (UTC)

Adding the [hide] link

I'm not that proficient in Wiki to do that. but can anyone add the [hifrf] link to this template? It is to big and gets too much space. Samuel Sol (talk) 13:41, 21 December 2007 (UTC)

A common misinterpretation of polycyclism here

...is, that a polycyclic (e.g., bi-, tri-, tetracyclic) compound is made out by the overall number of rings in their structure; this is wrong. In fact, the number of rings fused defines, wheter a compound/molecule is mono-, bi-, tri-, tetra- etc. cyclic. To illustrate this: trazodone is sometimes reffered to as a tetracyclic, but it is bicyclic. Amoxapine isn't tetracyclic, but tricyclic. Haloperidol isn't tricyclic. Venlafaxine isn't bicyclic. etc. etc.. This issue should be cleared with aid of some users contributing to Chemistry.--84.163.110.20 (talk) 17:14, 15 April 2008 (UTC)

NDDIs and Agomelatine

"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". Int J Neuropsychopharmacol. 2007 Oct;10(5):575-8. Epub 2007 Aug 6. PMID 17681087 I wish the abstract would mention it clearly, but it doesn't. A quick googling of the statement shows that Stahl stated it. Dr.Stahl being the authority he is in psychopharmacology, I would think NDDI as a new category and Agomelatine being its first member is warranted. NDDIs and NDRAs are different in that NDRA act directly as releasers while NDDIs act indirectly via disinhibition. One could argue about Agomelatine being a "Melatonergic antidepressant", but it is recognized that Agomelatine antidepressant effects comes from its 5-HT2c antagonistic properties; the melatonergic effects are side effects. Good side effects, sure, but only side effects as melatonergic agonism has never been proven being antidepressive and already has even been theorized to be depressive. The accent on it being the "first melatonergic antidepressant" is only a marketing strategy by Servier to differentiate its product. Other selective NDDIs are being currently developed, like TIK-301/LY156735. --WhereIsMarty (talk) 09:37, 28 August 2009 (UTC)

After giving it some more thoughts, I think it would be wiser to find at least another drugs which main mechanism is NDDI inducing before implementing this category. Fluoxetine (Prozac) is now considered a NDDI since it's now thought that its antidepressant effect is way more attributable to it's 5-HT2c antagonism property than its SERT inhibiting one. BUT, I fear that migrating Fluoxetine in NDDI isn't possible even if science agrees. So, I have to do some research to figure out if there's other candidate to justify the creation of the NDDI category. --WhereIsMarty (talk) 05:21, 30 August 2009 (UTC)