Talk:Duloxetine/Archive 1

Archive 1

Use of Statistics

The article states that "Five people . . . committed suicide while Eli Lilly was conducting preliminary trials." But five out of how many total? The linked NY Times article says 9,000, but I myself don't know enough about this topic to add the information myself.

--Skb8721 18:07, 24 September 2006 (UTC)

Um, yeah. That's an incredibly bogus statement to just put into an article. And just because the NYT is also crap at statistics doesn't make it encyclopedic information. Five out of how many? How many in the control group? Reference to the study itself? Not present. I've removed the line from the article in the meantime; it was:

Five people, including a 19-year old college student, committed suicide while Eli Lilly was conducting preliminary trials. (ref)G. Harris (2004): The New York Times

I appreciate whoever put it there did so thinking it was useful information, but it doesn't actually tell the reader a damn thing - stated as is, it's scaremongering. If there's a real problem that's encyclopedic information, it needs more than one piece of newspaper bad science - David Gerard 18:26, 8 October 2006 (UTC)

Salt form

The hydrochloride part of the molecule is not the pharmacologically active portion of the molecule, so I've removed it from the intro to the article (as per WikiProject Pharmacology standards). Fuzzform 23:19, 28 May 2007 (UTC)

Controversy neutrality

Is there anything specifically in the current version of the controversy that is disputed as POV? If not the template should be removed. Neitherday 14:45, 28 April 2007 (UTC)

Much of the text was originally written by someone with an obvious bias towards Eli Lilly, but I think most of the text is OK now, although it's not clear to me why the financial section is included in controversy. I am not totally comfortable with removing the template yet, but I am putting the financial in a separate section. 66.75.247.88 08:10, 30 April 2007 (UTC)

I moved the POV template to the financial section, since that is where the problem is. Neitherday 14:06, 30 April 2007 (UTC)

. —Preceding unsigned comment added by 72.95.16.67 (talk) 04:50, 9 November 2007 (UTC)

The most important section

As is typical for articles of this kind written in an adversarial tone, the article lacks a sensible paragraph that lists the positive trials and the indications for which it has been succesfully approved. This doesn't just belong in "history". Doctors would normally only prescribe a medication if there have been studies showing a benefit. I have certainly seen duloxetine used for chronic pain - if there have been studies these need to be mentioned. JFW | T@lk 06:24, 14 May 2008 (UTC)

Doctors, being merely humans, often prescribe medications under the influence of company salesmen and do not usually read critical reviews in French. On the balance, duloxetine does not appear to be a great medication. Thus it may be argued that the most important part here is the side effects part. Paul Gene (talk) 10:54, 14 May 2008 (UTC)

So far, all I have seen from Prescrire Int is gloomily negative reviews, often quoting data that is not otherwise accessible and therefore not open to verification.

"On the balance", I submit, reflects your conclusions after reading this article. Or have you other sources that we ought to know about? JFW | T@lk 14:12, 14 May 2008 (UTC)

Before anyone asks, I can't think of a single instance when I prescribed this drug personally, nor have I been bowled over by drug company representatives or dazzled by clinical trials. It's just that every time I review this article I am astounded by the hostility, assumption of bad faith and overemphasis on so-called side effects (every SSRI can cause hyponatremia, why put so much stress on a single report here?) JFW | T@lk 14:32, 14 May 2008 (UTC)

There are two major problems with duloxetine - hepatotoxicity at higher doses and suicides of healthy volunteers. They are the main reasons why Lilly's application for SUI indication failed. Paul Gene (talk) 18:33, 14 May 2008 (UTC)

In none of the SUI trials was there any report of hepatotoxicity. How many events were there - or rather what is the source that this was the reason for failing the application? And do you have any idea why the Europeans were not worried by this? JFW | T@lk 11:54, 15 May 2008 (UTC)

CT Registry ID# 6192. ~ 600 patients with SUI/MUI exposed to 80 mg duloxetine for ~250 days.

Elevations above the upper limit of normal for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase values were observed on at least one occasion of 14.8%, 9.4%, and 6.8% of subjects, respectively. TEAEs related to hepatic analytes were reported as follows: 4 for liver function test abnormal, 3 for hepatic enzymes increased, 2 for alkaline phosphatase increased, and 1 for ALT increased. Overall, 4 subjects discontinued from the study from liver function test abnormal, 2 subjects discontinued due to hepatic enzymes increased, and 1 subject discontinued due to ALT increased. Seven subjects reported the TEAE of CPK increased; 3 of whom discontinued from the study. (A subject is considered at-risk for a given laboratory analyte and abnormality category (Low, High, or Positive) if there was at least one baseline measurement for that laboratory analyte and that category of abnormality was not present for any baseline measurement. An abnormal postbaseline laboratory result is considered treatment-emergent if the subject is at-risk for that abnormality and the abnormality was not present for any baseline laboratory assessment.) And are not French - Europeans? Paul Gene (talk) 16:24, 15 May 2008 (UTC)

I am returning the Prescrire-based summation of risks and benefits of duloxetine into the lead - that is exactly what the lead should have. A personal dislike of Prescrire cannot be the basis of removal. Paul Gene (talk) 10:44, 15 May 2008 (UTC)

I have given additional arguments, which you have not addressed. This journal is certainly not the final word on pharmacotherapeutics. JFW | T@lk 11:54, 15 May 2008 (UTC)

Are not suicides of healthy volunteers sufficient? If not, I also given you the data on toxicity above. Prescrire is not a final word, but it is independent; and some well-known people write for it. Paul Gene (talk) 16:31, 15 May 2008 (UTC)

Duloxetine Pharmacodynamics

I attempted to edit the following information:

"When serotonin and norepinephrine are released from nerve cells (neurons) in the brain they are reabsorbed into the nerve cells through reuptake. Duloxetine works by preventing serotonin, norepinephrine, and to a lesser extent dopamine from being reabsorbed into the nerve cells in the brain, specifically on the 5-HT and NE and D2 receptors respectively."

To this:

"After serotonin and norepinephrine have been released from neurons into the synapse, they are reabsorbed back into the presynaptic neurons through reuptake by transporter proteins. Duloxetine works by binding to and inhibiting the transporter proteins for serotonin (SERT), norepinephrine (NET), and to a lesser extent, dopamine (DAT), thus preventing reuptake, and allowing the neurotransmitter to remain longer in the synapse. This results in increased stimulation of the postsynaptic neuron."

Doesn't seem to have updated correctly, but that might just be a problem on my end. The original version was nonsense. Duloxetine is not known to bind to any neurotransmitter receptors, only reuptake proteins. From the prescribing information (available at http://pi.lilly.com/us/cymbalta-pi.pdf):

"Preclinical studies have shown that duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine reuptake. Duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, and GABA receptors in vitro."

If someone thinks its necessary, I can probably edit this section to be more accessible to a general audience, but I figure it's much better to have accurate and inaccessible information than basic information that's just plain wrong. —Preceding unsigned comment added by 131.247.152.4 (talk) 06:47, 21 May 2008 (UTC)

Paul gene (talk · contribs) removed it. I'm not sure whether it should have been removed, but I had previously tagged it with {{fact}} because such wide-ranging claims on method of action need a solid reference. Is this pharmacodynamic profile inferred from its effects, or have there being neurochemical studies that confirm its properties? If such a reference can be provided, I'm sure that we can return your contribution. JFW | T@lk 11:29, 21 May 2008 (UTC)

Duloxetine vs pelvic floor exercise + bladder training

The current chapter on SUI (duloxetine#stress urinary incontinence) selected only favorable for duloxetine conclusions of University of Minnesota analysis (PMID 18268288). It skips over the unfavorable comparison of duloxetine with other drugs and non-pharmacological therapies. The whole story must be presented.

Currently, duloxetine#stress urinary incontinence states: "...concluded that duloxetine did not lead to cure of stress urinary incontinence in the vast majority of people, but that episodes of incontinence were reduced by about 50%. This was associated with an improvement in quality of life measurements. Mild side-effects were common, and about a fifth had to discontinue the medication because of poor tolerance." That is selective and inaccurate reporting.

The abstract of the study (PMID 18268288) points out: "Compared with regular care, pelvic floor muscle training plus bladder training resolved urinary incontinence (pooled risk difference, 0.13 [95% CI, 0.07 to 0.20]). Pelvic floor muscle training alone resolved or improved urinary incontinence compared with regular care, although the effect size was inconsistent across studies. Oxybutynin or tolterodine resolved urinary incontinence compared with placebo (pooled risk difference, 0.18 [CI, 0.13 to 0.22]). Duloxetine compared with placebo improved (pooled risk difference, 0.11 [CI, 0.07 to 0.14]) but did not resolve urinary incontinence, with no significant dose-response association."

The full text of the study (open access here http://www.annals.org/cgi/content/full/148/6/459#F2) states: "Review of 10 RCTs (71–78, 128, 129) (n = 3633) of duloxetine administered for 3 to 12 weeks in women with predominantly stress urinary incontinence concluded that the drug failed to show better curative effects than placebo... However, improvement rates and quality-of-life scores were better after duloxetine than after placebo (pooled risk difference, 0.11 [CI, 0.07 to 0.14]; I2 = 6%).

The study further states: "Moderate consistent evidence from 4 RCTs suggested that women with both types of urinary incontinence were continent more often after pelvic floor muscle training and bladder training compared with regular care (Figure 2) (96, 99, 100, 102, 103). Despite baseline differences in age, type of urinary incontinence, methods to measure continence, and quality of the studies (Appendix Table 2), a pooled risk difference of 13% (0.13 [CI, 0.07 to 0.20]) was consistent across the studies (Appendix Table 3). Pelvic floor muscle training and bladder training also improved urinary incontinence (absolute risk difference, 0.36 [CI, 0.10 to 0.61]), but improvement was not consistent across the studies."

In plain language, duloxetine did not cure any SUI while pelvic floor muscle training + bladder training cured 13% of the cases and oxybutynin or tolterodine cured 18% of the cases. In the terms of "improvement" (made better but not quite cured) duloxetine showed improvement in 11% of patients while pelvic floor muscle training + bladder training showed improvement in 36% of the cases. 71.244.121.113 (talk) 14:51, 1 February 2009 (UTC)

Page protected

Page sysop protected due to edit warring. Tan | 39 15:14, 25 February 2009 (UTC)

Bandolier

For DPN and fibromyalgia, there is fairly good data that duloxetine is effective. http://www.medicine.ox.ac.uk/bandolier/booth/painpag/Chronrev/Other/duloxetine.html JFW | T@lk 23:53, 3 November 2008 (UTC)

Agreed, pain is such a difficult condition to treat with many different causes this should be noted in the article..--Literaturegeek | T@1k? 01:14, 28 June 2009 (UTC)

Common sense: too much space for a topic, poor phrasing for a sentence and sarcastic criticisms

The critical sections seem to be far bigger than warranted. The number of people who experience adverse effects are far, far less than those who benefit. And effects like suicidality are so rare that no one study has shown statistical significance. Further, all anti-depressants and addiction treatment drugs carry this risk. Why? Because this side effect occurs not so much because of the drug as it does because of the person and his/her own situation. Some people have a lot of difficulty treating depression and addiction, and, in rare instances, these difficulties combined with drug treatment may result in the patient becoming suicidal. It's that simple.

Since this is the reality of this side effect, why is the section on suicidality so long and detailed? A small paragraph would be more appropriate. Please understand that I'm not trying to minimize this problem. It's very real. But, instead, I'm trying to give it an amount of space that's appropriate given its rate of occurrence. One could write a lengthy section on any number of unlikely side effects. Such a section may very well be accurate and comprehensive. But it also may suggest that that particular side effect is more common than it really is. The bottom line is that sections should be given an amount of space congruent with the significance of its subject. Is suicide significant? Of course. But it's so rare, that it's not more significant that details on the treatment of these disorders.

For the above reasons, I made a small change to the lede. The sentence in the intro on the critical reviews of Cymbalta suggested that these criticisms were more prominent & numerous than they actually are. Thus, I reworded it to be more accurate and less POV. Also, there was an ad hominem sounding quote from one of the critical reviews. It was sarcastic sentence that was in one of the reviews. However, it really has no place in this article. For now, I moved it down to the end of the "adverse effects" section. Perhaps it should be removed entirely. I'll leave that decision to those who are truly invested in this article (i.e. not me). Lastly, the sentence was unspecific. Who's writing these critical reviews? Users? Doctors? Researchers? How many negative reviews are we talking about? How does the number of negative reviews compare to the number of positive reviews? These questions are all important in deciding how to phrase a sentence of criticisms and how much space to devote to that issue. ask123 (talk) 05:13, 21 February 2009 (UTC)

The problem with Cymbalta is exactly that the side effects are very prominent and the benefits are limited. Please read the article. What you offer above is POV pushing and OR, which is not based on any science. WP guidelines ask to be careful with deleting factual information. You should add rather than delete. Why do not you add more positive information to the article? Lastly, you deleted references to the specific reviews, and then placed a tag requesting references. Instead of deleting and reverting lets discuss your objections point-by-point here.The Sceptical Chymist (talk) 11:22, 21 February 2009 (UTC)

There is no "problem" with Cymbalta. Perhaps the thousands of doctors and tens of thousands of people are wrong, or perhaps Sceptical needs to learn about NPOV.

There was no "problem" with Vioxx? Perhaps the thousands of doctors prescribing Vioxx and millions of patients taking it were wrong? Perhaps Mwalla needs to learn not to ignore the facts. Mwalla's main point is that if a drug (Duloxetine) is prescribed, therefore it has no serious side effects and its balance of risks and benefits is positive for all indications. Duloxetine is not a popular antidepressant - it was 10th among the antidepressants by the number of prescriptions in the US in 2007, behind an old tricyclic drug amitriptyline. If duloxetine is not popular despite the heavy promotion by Eli Lilly, perhaps it happened for a reason. If Mwalla has a POV, it needs at least to be based on some facts, not only on logical fallacies. Perhaps Mwalla also needs to learn Wikipedia etiquette and sign the posts. The Sceptical Chymist (talk) 21:57, 21 February 2009 (UTC)

This guy is really a hypochondriac. Please calm down and remember the NPOV policy. Not every drug is VIOXX. And, for your information, many people wish they could still take VIOXX 24.15.179.168 (talk) 00:11, 22 February 2009 (UTC)mwalla

If there are reliable sources which challenge negatives abouut the various points then we should add them to balance the article out towards Wp:NPOV with differing viewpoints. If undue weight has been given to a source and it has been challenged in other sources then it should be trimmed down.--Literaturegeek | T@1k? 01:23, 28 June 2009 (UTC)

NPOV Issues

There are sections on this talk page, above my own comments, that provide all evidence needed. It's OK to speak about a drug's problems, but even the second line implies the usage of a different medication. If at all, the article can be worded better, as to not disparage its subject. ^blurred_peace ☮ 19:12, 30 May 2009 (UTC)

"It is effective for major depressive disorder but appears inferior to the more popular antidepressants sertraline and escitalopram." Is there a reference existent for that line? It sounds like a POV to me. If it is indeed referenced, can someone make that line look a little better? ^blurred_peace ☮ 18:43, 30 May 2009 (UTC)

There is a reference for that in the body of the text. Please read the chapter Duloxetine#depression. Per WP:LEADCITE guideline there is no need to repeat the appropriate citation there: "with the exception of quotations, such sourcing does not need to be within the lead section itself: since the lead should summarise the body, there should normally be somewhere in the body where sources for the information can be placed." The Sceptical Chymist (talk) 22:50, 30 May 2009 (UTC)

I think that blurred peace is correct, there are serious NPOV violations. I have already started reviewing the literature on this drug and it really is not all that bad. Sure some antidepressants may be better overall but this drug may help some people which other supposedly "better" antidepressants failed them. This article and the paroxetine article are the worst I feel. I have made a start although I may stop if I get tired of editing them. We MUST reflect evidence based clinical guidelines and systematic reviews of the evidence based peer reviewed literature! :)--Literaturegeek | T@1k? 01:28, 28 June 2009 (UTC)

NPOV Noticeboard

I've created a summary of my concerns about this article here. I welcome outside opinions, comments, and ideas. ^blurred_peace ☮ 04:11, 24 June 2009 (UTC)

Thank you for doing that. I got your message on my talk page regarding this drug and paroxetine and have made a start in trying to make those articles more neutral. Unfortunately you get single purpose accounts who will do anything to demonise antidepressants, even having 100% of their edits demonising strong evidence based antidepressants which have a mainstream view of being effective both in the short and the long-term without significant development of tolerance! Some of these opponents of antidepressants become so fanatical that they will even promote benzos by distorting what sources say to make them say benzos are effective long-term as some sort of an "effective alternative" whilst demonising antidepressants as very harmful and ineffective. This is harmful and in the case of suicidal patients dangerous where the evidence says the benefits outweigh the risks. Are you happy with my edits so far? I can do much more work if I feel in the mood to do it. I am a good researcher. Regards :-)--Literaturegeek | T@1k? 01:32, 28 June 2009 (UTC)

NPOV tag was removed 3 May 2009 without justification

The user The Sceptical Chymist edited this article on 3 May 2009 and removed a neutrality point-of-view tag that I had placed in this article in September 2008. Please see the above history on the discussion page that describes the major neutrality conflicts that I and several other users such as JFW have pointed out. The Sceptical Chymist gave no justification for the removal of this POV tag and he/she performed this removal in the middle of a slew of ten successive edits. Even more disturbing is that The Sceptical Chymist also removed another tag which requested an expert to contribute to this page. In this case, The Sceptical Chymist provided an amusing summary of his edit: he said that "the expert is in ;)". So thankfully we now have a self-proclaimed expert who has made frequent successive edits to this article, and has removed critical tags from the article without justification.

This wikipedia page on Duloxetine has been suffering from major competing perspectives on how the introductory paragraph should describe the drug, and whether certain journal articles ought to be cited in the introductory paragraph. Before I return my NPOV tag to this article, I would like to get support from other contributors to this article that, in fact, the NPOV tag should remain. So, if you have anything to say about this, please give me some feedback. Also please check out for yourself the editing history of The Sceptical Chymist so that you can see the type of editing practices that we are dealing with. --Matthaller (talk) 17:36, 3 August 2009 (UTC)

Many changes have been made since then to this page. Literaturegeek, for example, inserted some positive information about the drug. I added more information on the conditions it treats. The return of the POV tag would be unjustified. The Sceptical Chymist (talk) 18:28, 4 August 2009 (UTC)

The Sceptical Chymist, You are right, many changes have been made since then and I do concede that the first paragraph is (in my opinion) a fair introduction to the drug and doesn't show any blatant bias. The second paragraph, containing the references to the "prompted critical reviews" in a European medical journal consisting of opinionated articles, is the area that I have a problem with. Personally I don't think these articles should be cited in the introduction at all (they should be cited in a risks/side effects section), but it's obvious that this ongoing editing war will keep those references there in perpetuity. At some point I would like to get around to reading those two papers in the French journal, I'm very curious to see what they say - however at my university our library doesn't have access to these journals; I can only view their abstracts on PubMed. Hopefully I can get around to it sometime. The Sceptical Chymist, I must thank you very much for your contribution to this Wikipedia article. It's important to have all view points appropriately represented. I especially appreciate someone who is an "expert" to be able to share their knowledge. You removed the "an expert on this subject is needed" tag from this article around 3 May 2009, saying that "the expert is in" in your edit summary. The Sceptical Chymist, please I would appreciate it very much if you could provide us with information describing any credentials which would qualify you as an expert. Your Wikipedia user profile says nothing about your history of expertise in this field. Do you have a degree from an academic institution in some pharmacology-related field? Have you published any peer-reviewed papers in scientific journals? Today I am replacing the "need of an expert tag" and I will happily remove it once you provide information which qualifies you as an "expert." Thanks very much. --Matthaller (talk) 03:44, 21 August 2009 (UTC)

It is hard to prove any credentials on WP, and I prefer to write here anonymously. Besides, "expert", in WP context is someone who has experience in editing this particular kind of article. You can choose to believe me or not but I have an advanced degree in an appropriate field, more than 20 publications and patents, and my work requires me to read 10-20 biomedical articles weekly.

As for why I used Prescrire and DTB (the later by the way is not French or opinionated)... Because the quotations from DTB and Prescrire are a fair summary of the appropriate parts of the article. In addition, if I wrote the summary of the data in my own words on such a controversial subject, I would have been accused in doing OR. The Sceptical Chymist (talk) 11:02, 21 August 2009 (UTC)

The Sceptical Chymist, I am curious, are you the same person that was formerly editing this article under the ID of Paul Gene? Or alternatively are you in regular communication with this individual? I simply ask because The Sceptical Chymist and Paul Gene have made extensive efforts to maintain quotations of the two articles from Prescrire and DTB in the introductory paragraph, despite much resistance from many contributors (shown in this discussion page). Also, The Sceptical Chymist or Paul Gene, are either of you authors on the referenced papers in Prescrire and DTB? If so, there is nothing wrong with this; I am simply curious.

I am going to concede this battle for the time being; The Sceptical Chymist is obviously a skilled and committed Wikipedia editor and I simply do not have enough time or energy to devote to counteract The Sceptical Chymist's persistent efforts to tightly control the introductory paragraph of this article. On a side note I'd like to make a small reflection/comment. The drug company Eli Lilly has spent tens of millions, if not hundreds of millions of dollars marketing the drug Cymbalta. However given the nature of Wikipedia and its "global peer review" character, Lilly's efforts to put a positive spin on Cymbalta can be totally thwarted by a dedicated Wikipedia editor such as The Sceptical Chymist. I would bet that some of the contributors to this page are on Lilly's payroll (though of course I have no proof of this). In any case Lilly is clearly losing the PR battle to The Sceptical Chymist on this Wikipedia article. --Matthaller (talk) 13:32, 27 August 2009 (UTC)

Is duloxetine "considered a first line treatment strategy for GAD"?

The lead of this article states that "It [duloxetine] is well tolerated and is considered a first line treatment strategy [for GAD]. There are two problems with this statement.

First of all, this wording misrepresent the original article PMID 19210191. PMID 19210191 says "This body of research suggests that duloxetine should be one of the options considered as a first-line treatment for GAD." Thus, the statement in the lead is much stronger than warranted by the citation.

Second, the principal author of PMID 19210191 is Susan G. Kornstein who has a strong conflict of interest. She received grant support and honoraria from Eli Lilly and served on the advisory board for Eli Lilly (see the disclosure here [2] ).

Is there a better reference from an impartial and respected researcher/research group to justify the strong statement in the lead?

The Sceptical Chymist (talk) 00:52, 22 October 2009 (UTC)

As you know I was the one who added that reference. Are you proposing to delete it or give it less prominance? Have you tried looking in pubmed or similar for a replacement?--Literaturegeek | T@1k? 01:02, 22 October 2009 (UTC)

The burden of evidence is on the person adding the information, see WP:BURDEN. The Sceptical Chymist (talk) 01:07, 22 October 2009 (UTC)

WP:MEDRS does not say papers by authors with affiliations to drug companies are seen as less than those which are not. I am not aware of any policy on wikipedia where we should treat a paper by drug companies differently. So it would come down to editorial consensus. I think that there is room for discussion and consensus. I will try and find a non-biased source over the next day or two to add to the discussion here. If I cannot find one then we can discuss the fate of the reference.--Literaturegeek | T@1k? 07:20, 22 October 2009 (UTC)

Well, although the policy does not spell it out, it would be in the spirit of Wikipedia to use a bona fide unbiased source. If such is unavailable, the statement in the lead should be moderated and qualified as, in effect, paid for by Eli Lilly or abandoned altogether. The Sceptical Chymist (talk) 14:45, 22 October 2009 (UTC)

I agree that a non-biased secondary source is preferable to a potentially biased secondary source. I think that if we are going to add a statement that one of the authors has a COI, that the ref that you provided,[3] should be added beside it so that we are providing a reference for her COI.

If we are going to delete the review article then here are some alternative papers.[4] and [5] I am not sure if the authors have a COI or not.--Literaturegeek | T@1k? 19:26, 24 October 2009 (UTC)

I checked other literature and think that the mention of duloxetine as first line drug for GAD should be scraped. The Maudsley prescribing guidelines only mention SSRI's, venlafaxine and some TCAs. Mayo clinic, among antidepressants mentions only fluoxetine (Prozac), paroxetine (Paxil), escitalopram (Lexapro), sertaline (Zoloft), venlafaxine (Effexor) and imipramine(Tofranil). Guidelines of Canadian Psychiatric Association only mention fluoxetine (Prozac), paroxetine (Paxil), escitalopram (Lexapro), sertaline (Zoloft), venlafaxine (Effexor) and imipramine (Tofranil). The Sceptical Chymist (talk) 22:33, 24 October 2009 (UTC)

Ok you have convinced me; I am okay then with the first line treatment strategy being deleted.--Literaturegeek | T@1k? 00:12, 26 October 2009 (UTC)

confusing lead

The lead is a kludge between 2 different POVs, and should be re-written to either be one NPOV, or to clearly show 2 different POVs. The intro says first that this med is "as effective as venlafaxine", but then says that this med should not be used for depression. Reading through this talk page shows some controversy aboutn this med, so I won't be re-writning. —Preceding unsigned comment added by 86.10.142.176 (talk) 23:13, 25 December 2009 (UTC)

Side Effects

The Literate Engineer 21:50, 19 February 2006 (UTC)

What are the side effects of taking Duloxetine?

---

Although Duloxetine (trade name: Cymbalta) is a serotonin and norepinephrine reuptake inhibitor, while Buproprion (trade names: Wellbutrin and Xyban) is a dopamine reuptake inhibitor, I find their effects very similar. Your Mileage May Vary. Perhaps they seem similar to me because they are the only treatments for depression which are effective for me (and I've tried nearly every other medication available).

Cymbalta tends to make one feel energetic, but also increase anxiety. During the first two to three days when I begin taking it, I experience "psychedelic" side-effects such as exaggeration of perspective; this would be familiar to anyone who has taken LSD. However, these effects are mild, and either goes away very quickly, or perhaps one simply adapts to it.

The most noticeable side-effects, for me, are dry mouth and difficulty sleeping. I get relief from dry mouth by chewing gum and using Biotene mouthwash. For sleep, I take amitriptyline (which is also indicated for fibromyalgia, a chronic muscle disorder I have). If that is not sufficient, I also take Trazodone. These are both tricyclic antidepressants. I take much smaller doses than would someone taking them for psychoactive effect to relieve depression. (Tricyclic antidepressants have become unpopular. At sufficient doses to treat depression, their side effects are difficult to tolerate.)

What little relief I've had from the popular SSRIs (selective serotonin reuptake inhibitors) such as Prozac, Zoloft and Luvox, typically it takes a month or more to be felt. Whereas with Cymbalta and Wellbutrin, I usually feel significantly less depressed within a few days. Unfortunately, during periods of extremely severe depression, I find that higher doses of these medications do not help, but merely increase the severity of the side-effects. When that happens, my best strategy is to focus on the feelings or life events which are causing the depression. (That's something I should already be doing. Drugs are not a panacea. But in my case, sometimes I reach a point where to take more drugs is no longer helpful.)

A common problem with antidepressants is that they all have side effects which are distressing to greater or lesser degrees, depending on the individual's specific response to the drug, and also which side effects one finds more tolerable than others. The side-effects begin as soon as you start taking the medication, while the beneficial effects (reducing or stopping depression) take longer. This makes it difficult to remain patient and keep taking the drug. Especially for someone whose depression (as it usually does) alters their thinking in such a way as to make them feel there is little hope.

All of these medications affect different people in unique ways. If you are seeking pharmaceutical treatment for depression, try to wait about two months to be sure whether or not a new medication is working. If it's not, try something different. Of course, this should be done under the supervision of a psychiatrist; MDs in other specialties are rarely well-informed about antidepressants. Also: pharmacists are often better sources of information on medications than doctors.

IMPORTANT NOTE: DON'T stop taking Cymbalta abruptly - I ran out for 2 days, and even when I resumed the medication I had nightmares that left me terrified to go to sleep. —Preceding unsigned comment added by 114.74.185.230 (talk) 13:36, 11 March 2010 (UTC)

Good source of info on medication effects and side-effects: http://www.rxlist.com/ drone5 00:04, 12 December 2005 (UTC)

Anecdotal adverse effects

I have just removed large chunks of adverse effect-related content, either because it was uncited and just looked like a list of mayhem, or because they were isolated case reports. With regards to the case reports, they were potentially relevant (e.g. hyponatraemia) but I dispute that we need to cite every report. Rather, there are much more reliable sources, such as the postmarketing reports that we are already citing (and they already include hyponatraemia). Duloxetine is approved for certain uses and indeed recommended and prescribed for certain conditions (e.g. painful diabetic polyneuropathy in the UK). We have a certain responsibility in giving a balanced view of a drug, and I think this is where we need to draw a clear line. I certainly do not wish to see the uncited list of complications return. JFW | T@lk 08:24, 22 August 2010 (UTC)

I have also revised the very heavy-handed intro that basically slammed the agent. Evidently, if it was that rubbish, NICE would not be recommending it for painful polyneuropathy. JFW | T@lk 08:51, 22 August 2010 (UTC)

Inconsistency of Fibromyalgia Indication Status

The entire article is bits and pieces written before and after the FDA approved Fibromyalgia indication for Duloxtetine. The article should be edited in its entirety to remove reference to the "pending decision by the FDA". John Holly (talk) 11:07, 21 February 2011 (UTC)

Controversial claim in first paragraph

The first paragraph of this article contains two statements that represent opinions rather than facts. That is, even though these statements cite articles from scientific journals, they clearly hold a bias against the use of this drug.

Duloxetine (brand names Cymbalta, Yentreve) is a serotonin-norepinephrine reuptake inhibitor (SNRI) used for major depressive disorder (MDD), generalized anxiety disorder (GAD), pain related to diabetic neuropathy and fibromyalgia and in some countries for stress urinary incontinence (SUI). It is manufactured and marketed by Eli Lilly. Large number of side effects occurring during duloxetine treatment and lack of clear advantage over existing medications prompted critical reviews concluding that duloxetine "should not be used" for stress urinary incontinence[1] and "currently has no place in the treatment of depression or diabetic neuropathy" as well.[2][3]

I contest the following statements as biased:

The stated "lack of clear advantage over existing medications" surely is disputable in the psychiatric/pharmaceutical community. If doctors are prescribing this drug, they obviously have confidence in its efficacy.

The statement that the drug "should not be used" for urinary stress incontinence may represent an opinion rather than a general fact. Again, if this drug is officially designed or prescribed for this condition, it indicates that at least some portion of the professional community have confidence in Cymbalta's efficacay for this condition.

The statement that Cymbalta "currently has no place in the treatment of depression or diabetic neuropathy" is inappropriate here. This again represents an opinion held by the author of this particular article.

I am fairly new to Wikipedia and do not know how this dispute should be resolved. Should this section be tagged as biased? Or should one of us just delete/change it? The statements should perhaps be moved to a controversies/side effects portion of this article.

--Matthaller (talk) 21:25, 7 September 2008 (UTC)

With reference to previous discussions, I too agree that the opening paragraph (as well as other sections of the article) is quite one-sided. I would suggest that you try to find different sources to complement those presently being cited, and BOLDly improving the intro. If you are reverted (which is possible), discuss the disagreement on this talk page and try to reach consensus (WP:BRD). Let me know if you need any assistance. JFW | T@lk 21:41, 7 September 2008 (UTC)

The statements are citations from independent reviews, which are quoted closely to the original so you should not remove them. If you feel that they present the medication in too negative a light, you can add references to the positive reviews. That will easily fix the problem. Also see the discussion above in Talk:Duloxetine#The_most_important_section. Paul Gene (talk) 21:47, 7 September 2008 (UTC)

I have read the above posts. Though these independent reviews Paul gene has cited from Prescrire Int and Drug Ther Bull represent an opinion rather than consensus, they certainly should be cited and quoted in this Wikipedia article. However, it is unjustifiable to quote these opinions at length in the introductory paragraph. To resolve this dispute I propose that we make the following changes:

1) State in the introductory paragraph that "like all antidepressants, side effects of duloxetine should be weighed against its potential benefits."

2) In the intro paragraph add citations to four articles supporting the efficacy of duloxetine.

3) Retain the citations to the three papers in the intro paragraph from Prescrire Int and Drug Ther Bull that Paul gene has cited, but remove the quotations from these articles.

4) Move these quotations removed from the intro paragraph to a new section of the article labeled "Criticism of duloxetine" or something similar.

The three of us (and anyone else that wants to participate) can surely come to a resolution that results in a comprehensive and clear article, and that does not marginalize any particular viewpoint. Before I make the changes I have described above, I want to see how Paul gene and JFW feel about this. There's no point in getting into an editing/reverting war here. --Matthaller (talk) 16:52, 20 September 2008 (UTC)

I would just like to add that the first part of this article is the worst I have ever seen in terms of bias. It's an opinion piece against the drug disguised with a few questionable, unduly-weighted, cherry-picked facts. Matthaller has some excellent suggestions for fixing it; I second them. I would probably even go further in pulling it back toward neutrality. I was really surprised when I read the top part of the article - I've never run across this kind of thing before despite using Wikipedia a lot. -- (Anon), 22:57, 23 October 2008 (PST) —Preceding unsigned comment added by 66.241.81.202 (talk)

There is no bias in the lead part. Prescrire is a French journal known for its common-sense critical reviews. Drug and Therapeutics Bulletin is a part of the respected BMJ (British Journal of Medicine) group, and its stated purpose is: "DTB's aim is to provide informed and unbiased information on medical conditions, medicines and other treatments to enable people to make informed choices. True to this objective, DTB has always been wholly independent of the pharmaceutical industry, Government and regulatory authorities. DTB is also free of advertising and other forms of commercial sponsorship." (see http://dtb.bmj.com/info/independence.dtl).

To the contrary, it can be argued that many (although not all) positive reviews and publications have been sponsored by Lilly or Shionogy and therefore are biased.

Weighing drug benefits vs risks is by necessity a matter of opinion. The critical reviews in respected journals reflect an opinion of a significant part of medical community. For that reason both positive and negative views on the balance of benefits and risks for duloxetine should be presented. 71.244.121.113 (talk) 00:43, 1 February 2009 (UTC)

Agreed positive and negative views should be presented, but not in the opening paragraph. The purpose there is simply to define the drug and its common uses. A section in the article for critisism of the drug would be an appropriate place to cite these two articles.

As for the articles' validity, I have read both and agree that the journals are respectable. However, the articles are opinion pieces by practitioners. Not to be dismissed for sure, but also not on the same level as a fully executed study. 67.160.162.79 (talk) —Preceding undated comment was added at 16:08, 1 February 2009 (UTC).

In general, if there is a significant controversy it should be reflected in the opening paragraph. The opening paragraph should give a summary for the whole article, not just indications. See WP:BETTER#Lead section: "The lead should establish significance, include mention of notable criticism or controversies, and be written in a way that makes readers want to know more." The authors in Prescrire and DTB are not just "practitioners" but independent practitioners selected for their knowledge of the field. I'll take their opinion over the supposedly positive studies presented by corporate spin doctors. Besides, independent "carefully executed studies" support Prescrire's and DTB's negative conclusions about SUI (see my note below) and depression (I'll follow up on that, if you want). 71.244.121.113 (talk) 16:30, 1 February 2009 (UTC)

I guess that's the issue. there ISNT significant controversy about this drug. There was in trials, and there might be questions about its indications now, but it's a widely prescribed drug. I dont doubt the validity of the two journals you insist on citing, but it's the equivalent to scanning the op/ed section of newspapers to find a letter to the editor that you agree with.

Your distrust of "corporate spin doctors" is probably good.Skepticism is always good.However, sometimes a drug does what it's supposed to do. "big pharma" loses billions on poorly made drugs. they try to avoid it. Just because you found some isolated articles and insist on putting them in the opening paragraph only makes you and Wikipedia look uninformed. It doesnt hurt Eli Lilly. Create a "controversy" section and put the info there. 67.160.162.79 (talk) —Preceding undated comment was added at 05:38, 3 February 2009 (UTC). ---The side effect profile of cymbalta includes an SNRI discontinuation syndrome that I found to be personally much more difficult to endure and much longer lasting than w/d from over 200mg of morphine taken daily for three years or any SSRI d/c, including the dreaded paxil, but also lexapro, prozac, effexor, etc. This from a substance marketed by Lilly (ad nauseum) (that may show some bias, oh well) as expressly and specifically as not only an anti-depressant, but an analgesic compound without any of the risk or difficulties of dependence associated with "narcotic" pain relievers. The term SS/SNRI discontinuation syndrome wasn't included in their literature until long after I had become physically dependent upon cymbalta. The d/c syndrome was so severe and disabling as well as resistant to normal titration down or titration aided by the cocktail of long acting prozac and the SSRI-like structured anti-emetic Ondansetron or Tramadol, that I remained on the (very expensive compared to other antidepressants) 120mg dose of duloxetine for over a year after I had realized it was ineffective and intolerable to my own system entirely because any attempt to taper down resulted in a condition that incapacitated my ability to operate machinery or sometimes walk or shower safely. Regardless of how many ways I tried to extricate myself, including breaking open the smallest available capsule (back then only the 30mg blue and white caps or the much more aesthetically pleasing sea foam green and blue 60mg caps were available) and halving or quartering that amount in the futile (for me) attempt to avoid brain zaps and vertigo by lowering the dose by tiny increments of first 15mg per 2 weeks, then I tried 7.5 mg per 2 weeks. I even tried through estimation to get as close to a 3.75mg reduction as possible. If I left for work in the morning and accidentally skipped my dose, by the afternoon I would have to excuse myself from work and take public transit home. I was only able to free myself from duloxetine when i was injured at work and given sufficient time to undergo the withdrawal effects safely at home with no commitments to drive or operate anything more dangerous than a television remote. This was over a year and a half ago and I still undergo the occasional bout of vertigo/nausea and brain zaps (all conclusively ruled out by neurologists, brain scans, and psychiatrists as due to no other etiology than SNRI D/C Syndrome.) I still contend that any claim of efficacy, mechanism of action, or comparative side effects for these drugs that were pushed through the FDA without evaluating anything other than the manufacturer funded studies of six or 12 weeks that the manufacture selectively submits (if results from study are positive) is delusional. The pathology of mood disorders is a mystery that scientists stab at in the dark, because the human brain is less understood than perhaps anything else on this planet. Case in point: why do we dream? where and how are memories stored? 5 or 10 years ago a pharmaceutical giant ran an advertisement that depression was caused by an imbalance of serotonin levels. This advertisement intended to convince people that their drug, an SSRI, restores that balance of seratonin and depression disappears. We now know it is infinitely more complicated, that myriad neurotransmitters play roles, and we are not sure which role what transmitter plays. Case in point: which has a larger role in depression: the 5-HTC or 5-HTC2 variant of serotonin? Why would medications that have no effect on serotonin like buproprion (Wellbutrin) be effective as an antidepressant? Still, we gather as gospel whatever new claim the same companies that are infamous for fraudulent claims and cover ups of negative elements and marketing passed off as science, because the PhD whose entire salary (and typically all-inclusive retreats to "conferences" in the caribbean or golf resort) came either directly or indirectly from a drug company says their company's drug works. And/or we saw it on the TeeVee. We are right now receiving all of our information on how and how well medications work indirectly from the giant pharmaceutical companies who have the money and power to control all "scientific" study and then bully the FDA into doing their bidding (check how much longer it takes a medication from a small outfit to get passed by the FDA and compare it to how long GSK or SKF, or whatever their latest merger is called (I cant keep track if it was Glaxo or French on the outs, but ...Smith/Klein...), Bristol-Myers-Squibb, or Eli Lilly required for approval) and it's as bad a conflict of interest and danger to the public as the Nuclear Regulatory Commission that simultaneously monitors, regulates, and then aggressively promotes/advises the proliferation of nuclear power plants. But people are much too moral and ethical to bend the truth in order to gain fortune, fame, or power, so why worry? If this article seems biased, it may be due to the fact that the people who really matter here, the sick who actually take these meds and deal with whatever effect (published or dismissed) arises, but have little other outlet to express their experience to a wider audience of similar sufferers wondering whether Cymbalta really does help both their pain and depression or anxiety or if it may make you sweat excessively, are reporting their unfiltered experience on their own time, without any personal gain other than the satisfaction that their report may clear up some of the pervasive lies and almost insurmountable bias created by drug companies with the power to invade yr homes through advertising on everything from radio, newspapers, magazines, television commercials, even TV news who are no longer above essentially disguising an advertisement as a news articles. Ever read a medical journal that doesn't cost a fortune and included no pharmaceutical advertising? If this is biased against one drug company over another, that i see as an issue, but biased against drug companies in general would be a good start. Honestly, all I read here is the lack of corporate bias so common in every aspect of our modern age, so common that actual bias seems balanced and honesty looks biased.

I have to agree that this opening paragraph is clearly biased and should be corrected. I am a medical professional who reads journals and scientific literature nearly every day and you can find several credible journal article that says one thing and then perhaps another in a minority view with a differing opinion. My point being is that their is no science to the statements used in the opening paragraph. They are the "opinion statements" of which are out of context with no scientific evidence that those "opinions" are based on. The person who has put them there clearly has an axe to grind for some reason against a drug that is widely prescribed. Patients deserve to have a more neutral discussion of the drug they are taking. Artful manipulation of the writing of this wikipedia article to satisfy the personal needs of one person's psyche is not fair and ultimately does more harm than good to the average layperson. I dont know if the person who insists on including biased statements had a bad experience with the chemical or works for a competing drug company. But I can tell you, this is the first time I have discussed neutrality in Wikipedia articles. I felt I should say that the first impression, was, who wrote this. It ruins the credibility of the entire article —Preceding unsigned comment added by 68.116.113.17 (talk) 6:09 am, 15 February 2009, Sunday (2 years, 6 months, 2 days ago) (UTC−5)

Scientific evidence from the reviews of risks and benefits of duloxetine as compared with the existing therapies is presented in Duloxetine#Major depressive disorder and Duloxetine#Stress urinary incontinence chapters. The lead just offers short conclusion summing up those chapters. If you can find review articles concluding that duloxetine is better than existing therapies for SUI or MDD, you are welcome to add them. The Sceptical Chymist (talk) 13:11, 15 February 2009 (UTC)

Duloxetine does not have to be better than existing therapies. But the article does have to be unbiased and fact based. Mwalla (talk) 17:12, 20 February 2009 (UTC)mwalla

Scientific evidence from the reviews of risks and benefits of duloxetine as compared with the existing therapies is presented in Duloxetine#Major depressive disorder and Duloxetine#Stress urinary incontinence chapters. The lead just offers short conclusion summing up those chapters. If you can find review articles concluding that duloxetine is better than existing therapies for SUI or MDD, you are welcome to add them. If duloxetine is worse than existing therapies than the lead is correct.The Sceptical Chymist (talk) 02:22, 21 February 2009 (UTC)

Just because an antidepressant is not statistically effective as other antidepressants does not mean it is a bad drug. Say 60% or whatever get a response from an SSRI, they will need to try another antidepressant with a different mechanism of action such as duloxetine and it may be the only antidepressant that works. What if a person has some contraindication or pharmacokinetical reason where other antidepressants aren't possible treatment choice. Duloxetine may be indicated for such patients. I think that you are throwing the babby out with the bathwater Sceptical Chymist.--Literaturegeek | T@1k? 01:13, 28 June 2009 (UTC)

Well, there is no way that any patient could take cymbalta, but not take some preparation of fluoxetine due to "pharmacokinetical" reasons as there is no active metabolite found in fluoxetine (developed by the same exact Eli Lilly scientists at around the same time) that will not result from duloxetine. The opposite could be true, as duloxetine is, in essence, a broader striking (or less selective, depending upon your personal bent) variant of fluoxetine.

--Just because a an anti-depressant therapy is effective in less cases total, does not mean these are the same cases as could be treated by other therapies. Brain chemistry varies enough between patients that one will affect one that will not affect another (for good or ill) at the doses studied. This is true for many drugs or therapies; for instance someone allergic to benedryl obviously won't find it effective for their allergies, and so just because benedryl is effective in more cases total does not mean it is appropriate for them! 67.169.49.52 (talk) 22:05, 1 August 2011 (UTC) Benedryl is ineffective mainly because it does not exist. Diphenhydramine (the INN of the antihistamine more commonly known by its original trade name Benadryl) is extremely effective, but also creates side effects (primarily drowsiness, but occasionally tachycardia) that makes it intolerable for some (Granted a cheap shot. Sorry).

Contradictory tag?

The article has been tagged as contradictory, but there is nothing on this discussion page which tells me why. 67.169.49.52 (talk) 22:08, 1 August 2011 (UTC)

Are you blind? I just explained that in the previous discussion topic. Do NOT remove the WP:UNDUE tag unless you actually plan on fixing the issue! SineSwiper (talk) 03:02, 4 January 2012 (UTC)

I can't find any explanation either, so I have removed the tag for now. -- Ed (Edgar181) 16:16, 18 August 2011 (UTC)

Six years later, still not NPOV

The intro is slanted. The intro should be for a summary of the drug, not whatever minority opinions might be found about it. "The role of duloxetine in the treatment of various conditions has led to divergent opinions." That's not a summary; that's a subsection starter. It doesn't belong here. Furthermore, the subsections are conflicted with two different POVs. This whole article breaks WP:UNDUE. Studies of certain negative comparisons are okay, but they really need to go in some other section, and it shouldn't switch POV mid-paragraph. Based on what I'm reading here, it sounds like Duloxetine will rape your dog and spit in your food. That's not the appropriate tone for the article.

Frankly, this whole article is terrible. It needs to be deleted and re-written. I'm going to repost it in the NPOV Noticeboard, and adding conflict/unbalanced templates to the article. Do NOT remove them until the article is fixed, else I will request an admin lock the page with the templates in place! And by fixed, I mean "rewrite most of the article". SineSwiper (talk) 23:26, 30 March 2011 (UTC)

Actually, the Undue template fits better. SineSwiper (talk) 23:36, 30 March 2011 (UTC)

I've had longstanding concerns about how this article has been stuffed with negative reports that are not really corroborated by the high-quality MEDRS-compatible sources that we should be relying on.

Could I request that you move to the talkpage any content that is obviously in violation of content policies. We can then build on whatever remains.

I think this article is perfect proof that the pharmaceutical industry has not attempted to use Wikipedia to provide rosy picture of their products. JFW | T@lk 01:26, 31 March 2011 (UTC)

Sure. I'll see about go back here when I have some time and cull out the bad spots. SineSwiper (talk) 12:40, 1 April 2011 (UTC)

Sorry, been pretty busy with various things, but this article is overdue for some mass editing. I'll start doing a bunch of that now in a new discussion thread. SineSwiper (talk) 03:26, 4 January 2012 (UTC)

---

"I think this article is perfect proof..."

The greatest trick the devil ever played... was convincing the world he didn't exist

                                                                        ---"Verbal" Kint.  — Preceding unsigned comment added by 70.172.222.139 (talk) 21:06, 17 August 2011 (UTC) 

Massive cleanup of UNDUE and biased information

Its efficacy relative to established treatments such as anticonvulsants and tricyclic antidepressants has not yet been studied.

Not appropriate for summary; not cited. This drug is obviously used for treatment of depression, so stating that it "has not yet been studied" is pretty far-reaching. Even if it was, it's not something for the summary paragraphs. SineSwiper (talk) 04:53, 4 January 2012 (UTC)

The role of duloxetine in the treatment of various conditions has led to divergent opinions. Owing to a large number of side effects and lack of clear advantage over existing medications, some reviews have concluded that duloxetine "should not be used" for stress urinary incontinence and "currently has no place in the treatment of depression or diabetic neuropathy." At the same time, some professional guidelines recommend duloxetine in chronic neuropathic pain, especially diabetic polyneuropathy for which it is first-line treatment, and as an add-on medication in stress urinary incontinence instead of surgery.

One, clearly out of scope for the summary. Two, the phrase "has led to divergent opinions" is weasel wordy at best and misleading at worse. Three, despite the references, this still breaks WP:UNDUE. The references don't appear to be primary sources, either. See WP:MEDRS. SineSwiper (talk) 04:53, 4 January 2012 (UTC)

In three out of six well-designed properly controlled pre-marketing trials duloxetine performed better than placebo; the three other trials were inconclusive.

Dead reference. Also, "well-designed properly controlled pre-marketing trials"? Who are we to say what is "well-designed" or "properly controlled"? Breaks WP:NPOV. SineSwiper (talk) 04:53, 4 January 2012 (UTC)

A meta-analysis of these trials indicated that the effect size of duloxetine as compared with placebo was weak-to-moderate, and similar to other 11 antidepressants studied. The rationale behind the development of duloxetine was that inhibition of the reuptake of both serotonin and norepinephrine would make it work better than selective serotonin reuptake inhibitors (SSRIs), which inhibit only the reuptake of serotonin. However, in a comparative meta-analysis of clinical trials duloxetine appeared to be insignificantly less effective than SSRIs. A head-to-head comparison of duloxetine with an SSRI escitalopram (Lexapro) found duloxetine to be both less tolerable and less effective. Another analysis of the comparative efficacy of modern antidepressants found duloxetine to be significantly, by 30-40%, less efficacious than mirtazapine (Remeron), escitalopram, venlafaxine (Effexor) and sertraline (Zoloft). Duloxetine was similar to fluoxetine (Prozac), fluvoxamine (Luvox) and paroxetine (Paxil). The tolerability of duloxetine was significantly worse than the tolerability of escitalopram and sertraline.

A review in Prescrire International summarizing the existing evidence noted that duloxetine has limited efficacy in depression and no advantages over other antidepressants. Prescribers observed that, taking into account the risk of hepatic disorders and drug interactions, there is no reason to choose duloxetine when so many other options are available. Similar analysis was presented by Drug and Therapeutics Bulletin, which is a part of the respected BMJ Group.

Negative, negative, negative, negative, negative. Appalling lack of balance and breaks WP:UNDUE again. Also, the norepinephrine additive was partially to stave off the sexual side effects (since NRIs tend to increase libido), not exactly to increase its effectiveness as an anti-depression med (though it might increase energy levels). Many psychiatrists won't touch SSRIs any more because of the side effects. And "insignificantly less effective"? What the hell does that mean? If it's "insignificant", that means it's not worth mentioning. SineSwiper (talk) 04:53, 4 January 2012 (UTC)

Stress urinary incontinence

Did not remove it, but most of the section needs some better balance. Either it's appropriate for SUI, or it's not, or there's some balanced opinions on the subject. SineSwiper (talk) 04:53, 4 January 2012 (UTC)

Eli Lilly is in Phase III of its FM trials and is expected to submit a sNDA to the FDA for approval of Cymbalta for FM within the next 12 months.

Dated information, contradicting the FDA approval statement on the end of the section. SineSwiper (talk) 04:53, 4 January 2012 (UTC)

According to researchers linked to Eli Lilly, clinical trials have demonstrated that duloxetine is well tolerated both in the short-term and the long-term. Other Eli Lilly dependent researchers suggested that duloxetine should be considered a first-line treatment for generalized anxiety disorder.

If the source is deemed unreliable by the editor themselves, then why put the damn information in? SineSwiper (talk) 04:53, 4 January 2012 (UTC)

In line with the general results, duloxetine use in depressed adults insignificantly decreased the odds of suicidality by 12% or 20% depending of the statistical technique used. However, in the subgroup of young adults (18–24 years old) duloxetine increased the odds of suicidality 5-fold, close to statistical significance.

First, the line before this one states "To obtain statistically significant results the FDA had to combine the results of 295 trials of 11 antidepressants for psychiatric indications. As suicidal ideation and behavior in clinical trials are rare, the results for any drug taken separately usually do not reach statistical significance." And yet, the editor feels the need to try to draw conclusions, anyway, using words like "insignificantly" and "close to statistical significance". "Almost" only counts for horseshoes and hand grenades! It especially does NOT count for statistical evidence.

Duloxetine was approved for use of stress urinary incontinence (SUI) in the EU in 2004. In 2005, Lilly withdrew the duloxetine application for stress urinary incontinence (SUI) in the U.S., stating that discussions with the FDA indicated "the agency is not prepared at this time to grant approval ... based on the data package submitted." A year later Lilly abandoned the pursuit of this indication in the U.S. market.

Didn't remove this one. In fact, this one is good. It should be SUI section above, not buried in this history section. The SUI section should be shortened a bit and summarized with something similar to this statement. SineSwiper (talk) 04:53, 4 January 2012 (UTC)

Hello SineSwiper. Thanks for finally doing what should have been done some time ago, instead of ramming tags onto the article. I have readded the references (originally added by me) to the introduction concerning its role in diabetic neuropathy and SUI. Please complete your changes and remove the tag as soon as possible. JFW | T@lk 13:22, 4 January 2012 (UTC)

Unclear phrasing

In the Fibromyalgia section: "The change in the level of women's pain was particularly pronounced after a month of taking the drug, then leveled off a bit before dropping again near the end of the study."

In this sentence, what does "dropping" mean? The change (presumably improvement) dropped? Their pain levels dropped? These two contradictory ideas could both be read from this phrasing.

Pollifax (talk) 13:20, 28 July 2013 (UTC)

Patent Loss

It is claimed on this page that Eli Lilly loses their patent on Jan 1, 2014.

I just bought Duloxetine 60mg capsule (Lupin), generic for Cymbalta here in northern Virginia. Here is an article on www.medicinenet.com saying it was approved December 11.[6] Donpayette (talk) 01:36, 19 December 2013 (UTC)

"Medical uses" section missing "major depressive disorder" subsection

The first in the list of medical uses is "major depressive disorder", yet there is no subsection for it at all. — Preceding unsigned comment added by 97.97.239.233 (talk) 16:22, 18 February 2014 (UTC)

"Controversy" section considered harmful

That entire section reads like four paragraphs of disguised CCHR propaganda and needs to be drastically rewritten. Totally inappropriate for Wikipedia. Haikupoet 07:26, 29 December 2006 (UTC)

Agreed: This article needs a lot of cleaning up and editing. It is totally sensational. --Joyfulpotato 02:34, 26 January 2007 (UTC)

A certain [user 67.82.232.151|user:67.82.232.151] has a clear bias against the Eli Lilly Corporation, and has single-handedly added the vast majority of the current 'Controversy' section. Since one guy with a grudge has had such a huge effect on this page, I’m adding a POV tag. I know nothing about the industry myself, but until someone can verify this information we should let people know what’s what.

Here are some of his edits to the Eli Lilly page:

Eli Lilly has been known to engage in withholding internal information on medications, including Prozac, Thimerosal and Zyprexa in order to downplay side effects and adverse reactions in order to boost profits. [7]

Consequently, many critics claim that the FDA approval of duloxetine for Major Depressive Disorder (MDD) and diabetic neuropathy is irresponsible and intellectually dishonest, and is a case illustration of the agency's failure to prevent harmful drugs from being marketed in the name of big profits. [8]

In one of the only three cases to ever go to trial for SSRI indication in suicide, Eli Lilly was caught corrupting the judicial process by making a deal with the plaintiff's attorney to throw the case, in part by not disclosing damaging evidence to the jury. [9]

Over the last decade, the company spent millions of dollars lobbying Congress in hopes of extending its patent on Prozac and some lawmakers even attempted to insert last-minute provisions to omnibus spending bills to grant the company’s wish. Generic drugmakers prevailed, handing Eli Lilly one of its few legislative losses in recent memory. The company, which favors Republicans over Democrats with its contributions… [10]

This same user also started the ‘Controversy’ statement on the Duloxetine page, containing the following outsourced and obviously biased statements:

In the 1980s, [Eli] Lilly waged a successful campaign to get fluoxetine, brand name Prozac, through the FDA even though not a single study submitted to the agency showed the drug to be effective for depression when taken alone. …not only targets serotonin, it also impacts another important neurochemical, norepinephrine. This flatly contradicts the ‘serotonin/good, norepinephrine/bad’ story that launched the SSRI revolution that [Eli] Lilly started with fluoxetine. [11]

He started a ‘Legal’ section on the Olanzapine page with this:

…documents given to The Times by a lawyer representing mentally ill patients, show that [Eli] Lilly executives kept important information from doctors about Zyprexa’s links to obesity and its tendency to raise blood sugar — both known risk factors for diabetes. [12]

He adds this unsourced statement to the SSRI Discontinuation Syndrome page:

Data obtained from 9 clinical trials assessing the efficacy and safety of duloxetine in the treatment of major depressive disorder (MDD) by Lilly Research found that patients with discontinuation-emergent adverse events (DEAEs) were reported by 44.3% of duloxetine patients… No follow up was published by [Eli] Lilly stating the duration of DEAE's longer than one week ultimately persisted for. [13]

--70.17.209.58 09:02, 22 March 2007 (UTC)

If any of the statements are verifiable, then surely they should be included. If they are not, they should be removed. Neutral Point Of View is all well and good, but if we're just having a blanket removal of anything that seems biased (even if relevant and verifiable), then that is also a POV issue. Include all that is relevant and verifiable, however uncomfortable it is. Wikipedia is not censored. 2.97.135.148 (talk) 12:03, 17 April 2014 (UTC)

Citation for contraindication with Amphetamines

There appears to be a problem regarding the "harmful interaction with amphetamines" section, as it is attributed to a footnote (27) that refers to harmful interaction with Triptans, not amphetamines. — Preceding unsigned comment added by Lorfa (talk • contribs) 00:20, 15 May 2014 (UTC)

Prescrire????

The following discussion is closed. Please do not modify it. Subsequent comments should be made in a new section.

"Prescrire has stating that duloxetine is potentially more harmful than beneficial due to its greater side effects and thus lists it in its 2014 list of drugs to avoid.[4]"

Prescrire? You can pretty reliably find negative quotes about most drugs there, but according to this site the average Prescrire paper was cited 0.17 times over the last 3 years, with half of these citations being from other Prescrire papers.

By comparison, the average BMJ paper was cited 12.5 times (95% external) and even the Journal of Orofacial Surgery got 2.5 cites per article (100% external).

Not a great drug, but do we need to reach this far into the barrel for a citation? Prescrire panned lenalomide ("should only be considered in clinical trials"), though it is a preferred regimen for MM by the NCCN, ESMO, and the British Society for Haematology, panned daptymycin ("no advantage") which is a recommended treatment in many IDSA guidelines, and thought little of linezolid as well. Its clearly not a mainstream publication.

Ultimately, Prescrire is WP:SELFPUBLISH. The manuscripts are written by the editorial staff, and the "reviewers" are handpicked by the staff themselves. In most cases, according to the Prescrire website, the editorial staff makes up a significant portion of the reviewers. Unlike the case of a real journal, there is no element of independence. While the editorial staff of a real journal can control content by selecting sympathetic reviewers, they at least cannot control the subject matter and content of the articles that are submitted.

Formerly 98 (talk) 15:13, 28 June 2014 (UTC)

It is a very well respect perspective from France. Including it increases our global nature. We are already too US centric. And really its conclusions are inline with the Cochrane review. Additionally it is a not for profit and each article is a systematic review and peer reviewed by 20-40 experts. Doc James (talk · contribs · email) (if I write on your page reply on mine) 00:52, 29 June 2014 (UTC)

Well, no disrespect, but werent you just on the medicine talk page discussing the need to restrict the use of low quality journals as sources? And here you have thrown BRD out the window to defend your citation of a self published journal that gets 1 citation for every 11 articles it published.

I'm old enough to know I won't win a fight on this. But I hpe you'll reconsider your position. A bad pharmacology journal has no more place here than a bad accupuncture journal. Respectfully Formerly 98 (talk) 01:19, 29 June 2014 (UTC)

• It is produced by a systematic review
• It is peer reviewed by 20 to 40 experts
• It is a not for profit
• It does not accept advertising
• It is independent of industry

This journal has a lot going for it. Doc James (talk · contribs · email) (if I write on your page reply on mine) 01:30, 29 June 2014 (UTC)

With respect to the SJR the difficult is that this is for "Prescrire International" which is the English translation of Prescrire. SJR does not appear to do not English journals. Doc James (talk · contribs · email) (if I write on your page reply on mine) 01:38, 29 June 2014 (UTC)

By the way their recommendations only pertain to France, thus stated that. Doc James (talk · contribs · email) (if I write on your page reply on mine) 03:34, 29 June 2014 (UTC)

RfC Is this content suitable

The following discussion is closed. Please do not modify it. Subsequent comments should be made on the appropriate discussion page. No further edits should be made to this discussion.

---

I propose adding "In France Prescrire has stating that duloxetine is potentially more harmful than beneficial due to its greater side effects and there being better agents available. Thus it has lists it in its 2014 list of drugs to avoid." I see adding a major non USA and independent opinion to be positive.Doc James (talk · contribs · email) (if I write on your page reply on mine) 09:38, 29 June 2014 (UTC)

Support

• Support Doc James (talk · contribs · email) (if I write on your page reply on mine) 09:38, 29 June 2014 (UTC)
• Support Seems reasonable in context. After all, it is a report of a statement in a reputable source, no? Not an allegation originating in WP. (Incidentally, the reason for the late response is that I have only now received the RFC!) JonRichfield (talk) 10:28, 21 July 2014 (UTC)

Oppose

Discuss

• Comment: Prescrire does not have a high impact and I am wary of using it as a reference since it may represent a small minority of professional opinions. It also represents a single country, France, and prescribing practices vary extensively between counteries. I would prefer not to see specific details from the Prescrire article here (such as the fact that duloxetine is on a "drugs to avoid" list). Instead, discuss the specific reasons why some clinicians believe duloxetine should be avoided, and cite appropriate papers for each reason. Roches (talk) 05:47, 9 July 2014 (UTC)

Follow-up: It seems the arguments against the drug are well supported now. Not sure how I missed this; I wrote the comment above several days after looking through the article. There are several indisputably high-impact, well-reviewed references in the article. So if Prescrire makes the argument more more succinctly than another source, I think it's okay to include. Roches (talk) 19:15, 12 July 2014 (UTC)

The discussion above is closed. Please do not modify it. Subsequent comments should be made on the appropriate discussion page. No further edits should be made to this discussion.

The discussion above is closed. Please do not modify it. Subsequent comments should be made on the appropriate discussion page. No further edits should be made to this discussion.

sleepy

How long do you have to take duloxetine before you are not so sleepy all the time? — Preceding unsigned comment added by 209.141.218.243 (talk) 03:38, 22 September 2014 (UTC)

Impartial links?

Should there the link to the manufacturer's website be there? Surely it's promotional? Also, outside North America direct-to-consumer advertising of prescription-only drugs is illegal.

In the same vane, should the manufacturer's logo be so prominently displayed? I understand that their marketing of duloxetine makes it most visible to the public, but wikipedia isn't meant to be a marketing tool. Let's discuss the chemical and move the corporate information to a section later in the article. Alvis 06:09, 23 April 2006 (UTC)

And anyway, the article isn't about Cymbalta, it's about duloxetine. -Etoile 21:20, 20 May 2006 (UTC)

i had the misfortune of taking this... it took a week of almost continuous morphine to keep my migraines in check. i think it will be pulled from the market -Lieutenant Colonel Frank Slade 07:41, 17 June 2006 (UTC)

"Long-term side-effects seen in these trials did not vary from the original approval studies." <-- ?? is that really needed? doesn't flow in my mind, but I'm not removing it. -- Lieutenant Colonel Frank Slade 13:57, 2 July 2006 (UTC)

IMHO, links to the manufacturer's website should be included, though a display of the company's logo should not, and the generic name clearly identified [currently the Wikipedia page meets these suggestions]. On the manufacturer's site should appear the prescribing information and, among other things, all the incidences of side effects that occurred during the clinical trials that were reported to the FDA. Unfortunately, such information is not always easy to interpret; although the number of occurrences of a particular side effect are reported vs the number of occurrences for a placebo, there is no assurance that the side effect was a response to the drug, only that it occurred to a patient taking the drug. If the incidence is high relative to the placebo, then there is a greater probability that that it is a common side effect. On the other hand, because some individuals respond differently (for many possible reasons), a low incidence of a side effect may still be a response to the drug. In any case, the FDA requires that the manufacturer report all this information and it can be valuable to the patient. The average user should of course be aware that the promotional blurbs on the manufacturer's site should be weighed against other treatment options. I would say consult your doctor, but I have often seen the same promotional promotional information in pamphlets inside the doctor's office. Caveat Emptor! After you visit your doctor, talk the pharmacist, sometimes they know more than the doctor. Janopus (talk) 18:25, 13 January 2009 (UTC)

Impartial Investigative Pages / Links

In my opinion, there should be allowance for impartial references or links that point to a page where real people cite their experiences with this medication. I'm not talking about personal blogs. I'm talking about impartial sites where anyone can write about their true experiences with this medication via a form that has standards for empirical consistency and the elimination of stray variables. I feel it has encyclopedic value, and it is especially important to list such sources in an article that has so much controversy surrounding its content. More specifically, I am referring to the deletion of RxStories - Cymbalta ( duloxetine ). The notes included a statement that said it is "the worst kind of external links". With all due respect for everyone trying to make this article the best possible resource, I do feel this may have been a hasty decision that needs to be re-examined. One of the things that makes Wikipedia so wonderful is the fact that we can reference and link to diverse sources on the Web that enable readers to gain a full perspective. This is something that no other encyclopedia can do effectively. It makes Wikipedia unique and extremely valuable to researchers. Please wait for further discussion before deleting this again. APatcher (talk) 07:41, 9 October 2011 (UTC)

I can think of a large number of reasons why this is a bad idea. For one thing, nobody has actually submitted any experiences with duloxetine you the site yet. It is also not clear whether contents will be moderated, the experiences will be completely unverified and could easily be generated by competing drug companies etc.

The link will stay deleted, because it fails WP:ELNO. JFW | T@lk 08:37, 9 October 2011 (UTC)

NPOV

[[ == This article sounds like an advert written by the drug company itself... There are no side effects, No study texts A link to the manofacturer website And the technical language which usually appears in this kind of Advert. ==]]

I don't know how much this will help, but there are some particularly deleterious side effects. If you miss a dose, it hits you like a sledgehammer...you'll have headaches diarrhea, constant sweating, and a general feeling of malaise and weakness. I believe that this is due to withdrawal from the norepinephrine, as it's half-life within the body is relatively short as compared to serotonin. I had a brief discussion with my doc about this, and he esentially confirmed it, but this is just heresay evidence. Take it for what you choose 72.44.0.76 23:02, 20 September 2006 (UTC)

Suicide as a side-effect?

Stories about Cymbalta/Duloxetine I do not know if this story is true or not!! But I think for the sake of discussion it should be considered. I came across this article because I was researching the medicine my wife was prescribed.

It is true that some anti-depression drugs have this suicide side effect according to some traditional Chinese medicine doctors, such as Hai-Sha Ni --Leo 05:35, 12 December 2006 (UTC)

A side effect of *depression* is suicide. It would logically follow that people taking anti-depressants would in some cases commit suicide. --204.210.233.175 20:49, 11 January 2007 (UTC)

Well, the most common explanation for the increased risk of suicide is that (rather than directly increasing thoughts of suicide) anti-depressants have an immediate effect upon your energy, which enables you to actually go through with the thoughts - the anti-depressant affect takes a bit longer. This is the explanation I've gotten from the most psychiatrists, at least. -Elizabennet | talk 19:55, 7 April 2007 (UTC)

I wonder if there is any actual evidence for that explanation. If there is, this would be something to include in the article. Neitherday 22:15, 7 April 2007 (UTC)

As far as I know, the mechanism for temporarily increased suicide rates is still a mystery. Another hypothesis is that people diagnosed with depression may actually have bipolar II, which involves hypomanic states that stand out much less strongly than the depressed states. SSRIs put them at increased risk of a depressed/impulsive mixed state, which can lead to suicidality. Inhumandecency (talk) 22:06, 18 November 2009 (UTC)

Anecdote is not data but I had read personal experiences that described having suicidal thoughts "for no reason", atypical of their personality. And in general, lots of complaints of "not feeling right"... "I don't feel like the same person", "my personality has changed" (in a bad way) by those on cymbalta. Givethemahug (talk) 14:16, 3 October 2014 (UTC)

Vertigo

I personally take this medicine and have encountered abrupt vertigo as a side effect. I also searched online and found this to be mentioned by many patients. I cannot, however, find a research document listing this as a side effect. Has anyone else found anything? Smeggysmeg 06:19, 22 February 2007 (UTC)

According to Eli-Lilly, vertigo is listed as a "frequent" side effect. Frequent is defined as occuring in at least 1/100. Others defined as frequent are: hot flush, anorgasmia/orgasm abnormal, dysguesia, lethargy, parasthesia/hypoesthesia, weight increase, chills/rigors, and palpitations. This in not a comprehensive list. Tunafizzle (talk) 07:41, 17 August 2008 (UTC)

I just started this med and my head is spinning. I've been taking Zoloft for some time; my dr. said I would probably feel the "positive" effects of Cymbalta more quickly because of that. Also, since I started taking it (less than a week now), I am having a big bad flare up of my fibromyalgia pain. THAT could be a coincidence - it's hard to tell with fibro. The dr. is hoping that the Cymbalta can take the place of not only the Zoloft but the pain meds I'm on as well - Tramadol and Neurontin. In addition to the fibro, he's treating me for an obnoxious OCD, where I am picking my scalp and pulling my hair out. (That sounds so awful, but I know there are other people who do it.)Meowfur29 (talk) 15:52, 15 September 2008 (UTC)Meowfur29

I have recently started this med also. I took one 30 mg capsule a few hours ago and now I feel nervous and (uncomfortably) stimulated.--Metalhead94 (talk) 19:46, 25 October 2008 (UTC)

Off label uses?

I've heard of Cymbalta being used off-label for adult ADHD and smoking cessation; perhaps a mention of off-label uses is noteworthy? (I personally know someone who was prescribed Cymbalta for ADHD) --danikayser84 ★ 15:38, 3 January 2015 (UTC)

Edits of Feb 26 2015

Hi Doc, "(→‎Fibromyalgia and chronic pain: adjusted as one ref says "oxycodone no better than placebo" and duloxetine worse than oxycodone)" - could you provide more detail here? Thanks. Formerly 98 (talk) 13:36, 27 February 2015 (UTC)

Here [14] says:

"The analyses found all treatments except oxycodone (frequentist) and hydromorphone (frequentist and Bayesian) to be more effective than placebo." (ie oxycodone as good as or worse than placebo)

"Indirect comparisons to duloxetine using the Bucher method found all confidence intervals but etoricoxib encompassed zero, indicating the differences between duloxetine and all treatments except etoricoxib were not statistically significant."

"This meta-analysis found no difference between duloxetine and other post-first line oral treatments for OA in the total WOMAC score after approximately 12 weeks of treatment in a consistent manner."

But than it says

"After adjustment for baseline pain score, however, duloxetine showed evidence of superiority to both tramadol and hydromorphone, but not for the other treatments, including etoricoxib."

So thus changed it to "may". Doc James (talk · contribs · email) 01:30, 28 February 2015 (UTC)

Yeah, seemed very long winded and hard to follow. Formerly 98 (talk) 02:26, 28 February 2015 (UTC)

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Neutrality

Hello everyone, there has been published a new scientific research on Duloxetine in comparison to placebo effects on chronic knee pain, since several parts of this article, particularly at the beginning, seem to be a bit too positive. Not that promotional, anyhow.
Please take a look at: http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002570
It would be fine, if one could add an information here and there. Thank you. Kind regards --BioExpress (talk) 07:03, 21 November 2016 (UTC)

primary source, we don't use them per WP:MEDRS. but thanks. Jytdog (talk) 09:17, 21 November 2016 (UTC)

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Heading

Unclear what sources support this stuff?

Doc James (talk · contribs · email) 01:12, 7 December 2017 (UTC)

"The duloxetine + mirtazapine combination is a particularly effective tool in the antidepressant arsenal. Duloxetine is a very high affinity blocker of both the serotonin and norepinephrine transporters, at 0.8 for the SERT and 7.5 for the NET respectively, resulting in increased serotonergic and noradrenergic neurotransmission, which results in improvements in mood, cognition, desire to work, motivation, greater skill at performing tasks effectively, memory, alertness, and keenness, while also alleviating depression, anxiety, and obsessive-compulsive ideation. Mirtazapine’s antagonism of the α₂ receptors further preserves and enhances serotonergic and noradrenergic neurotransmission and its very high antagonism of the 5-HT₂ receptors also alleviates depression and anxiety. Importantly, duloxetine is a moderate affinity inhibitor of the CYP2D6 enzyme, thereby increasing the plasma concentration of the substrate, mirtazapine, to between 2-5 times the normal levels. After beginning use of this regimen, symptoms such as prolonged headache, fatigue, and even a worsening of psychological symptoms tend to predominate for 3 weeks before going away. Therapeutic effects set in 3-4 weeks after beginning use, even if one has just discontinued a previous antidepressant."

References

Another version

"The duloxetine + mirtazapine combination is a particularly effective tool in the antidepressant arsenal. Duloxetine is a very high affinity blocker of both the serotonin and norepinephrine transporters, at 0.8 for the SERT and 7.5 for the NET respectively, resulting in increased serotonergic and noradrenergic neurotransmission, which results in improvements in mood, cognition, desire to work, motivation, energy, greater skill at performing tasks effectively, memory, alertness, and keenness, while also alleviating depression, anxiety, and obsessive-compulsive ideation. Mirtazapine’s antagonism of the α₂ receptors further preserves and enhances serotonergic and noradrenergic neurotransmission and its very high antagonism of the 5-HT₂ receptors also alleviates depression and anxiety. Importantly, duloxetine is a moderate affinity inhibitor of the CYP2D6 enzyme, thereby increasing the plasma concentration of the substrate, mirtazapine, to between 2-5 times the normal levels. After beginning use of this regimen, symptoms such as prolonged headache, fatigue, and even a periodic worsening of psychological symptoms tend to predominate for 3 weeks before going away. Therapeutic effects set in 3-4 weeks after beginning use, even if one has just discontinued a previous antidepressant.

References

This is strange. This review "Anttila SA, Leinonen EV (2001). "A review of the pharmacological and clinical profile of mirtazapine". CNS Drug Rev. 7 (3): 249–64. PMID 11607047." does not even mention duloxetine?

And neither does this one[15]

Many of the rest do not meet WP:MEDRS. Doc James (talk · contribs · email) 04:49, 16 December 2017 (UTC)

@Doc James: Hi! I'm the one who added that edit. A few of the links I added were done in expedience from, for example, prior information I had gathered from them that applied to this subject, such as the effects of 5-HT receptor antagonism which can be found in the mirtazapine link, or due to the difficulty of finding a scholarly review article for how long it takes for therapeutic effects to set in. However, the brunt of the information, such as the efficacy of the combination, the forms of improvement resulting from increased serotonergic and noradrenergic neurotransmission, and duloxetine's CYP2D6 inhibition, are all supported by the scholarly review articles and university medicine profiles I cited, such as the "Case for LRF, "Importance of norepinephrine in depression", and "Influence of serotonin on mood and cognition" studies. I think it's helpful for some individuals looking for a bottom line profile of efficacy to see information of the nature that I described. Just wondering what your logic was in removing it (maybe because of a few non MEDRS links?) and if you could give me some feedback and see if we could get the edit back in some revised form. Thanks! Reixus (talk) 08:26, 22 December 2017 (UTC)

Oh yeah, looking at the mirtazapine link more closely, I used that one just to describe the effects of mirtazapine's α₂ antagonism. Duloxetine's effects are described elsewhere. Reixus (talk) 08:42, 22 December 2017 (UTC)

Okay it needs to be based on sources per WP:MEDRS. Case reports are not suitable. Best Doc James (talk · contribs · email) 19:24, 22 December 2017 (UTC)