Talk:Fluoxetine/Archive 2

Archive 1

Archive 2

Reconcile

Reconcile (a proprietary drug for dogs) in a disambiguation list at http://en.wikipedia.org/wiki/Reconcile links to http://en.wikipedia.org/wiki/Fluoxetine. So far, so good. But there's no mention there of Reconcile. Since there's a link, we owe it to the reader to mention in the latter article that among SSSIs is also Reconcile, the chewable tab for dogs. One can glean this circumstantially (i.e. I have been sent here from there, so Reconcile must be an SSSI), but is that enough? Ajarmitage (talk) 07:10, 12 August 2009 (UTC)

I am not sure it is notable enough. Having a disambig link to the article does not mean the word have to be present there. Even the often made grammar errors in the name sometimes are included into disambiguation. The Sceptical Chymist (talk) 10:29, 12 August 2009 (UTC)

Prozac and personality

I took the liberty of adding this section in again with references. I think to have a wikipedia page on Prozac, and not mention its personality changing effects once, is kind of misleading. Although it only happens in a minority of people, the whole reason it became popular as an AD in the first place was because of these effects.

@Sceptical Chymist. What's your rationale for deleting in the first place? You said dubious, so I backed it with references... —Preceding unsigned comment added by Db0255 (talk • contribs) 06:24, 20 October 2009 (UTC)

I moved the paragraph in question below for further work. The sources you used do not pass the muster for acceptable sources in medical articles. The definition of reliable source is much stricter for medical articles, see WP:MEDRS. You used articles from news magazines and from a popular book by a psychiatrist based on his personal impressions. None of the sources you offered is a peer-reviewed scientific article. The paragraph follows below. The Sceptical Chymist (talk) 01:03, 22 October 2009 (UTC)

OK. That sounds good. If I were able to find the aforementioned articles, I think it would be wise to add this section back in don't you think? There are also news articles and other books, in the main Prozac article, why are those not changed? —Preceding unsigned comment added by 69.134.48.76 (talk) 02:59, 23 October 2009 (UTC)

If you are able to find the literature, a couple of sentences about the personality changes would be warranted in the section on side effects. More material could be distracting -- the space in the article should be proportional to the significance of the material.

As for the popular books and news articles, they are used in the "non-medical" parts such as History and describe "non-medical" facts: sales, patent expiration, court procedures, press reaction. You could, perhaps, insert the "character changes" hypothesis into the popular culture or controversy category. In that case, it would still be very desirable that this hypothesis either confirmed or debunked by an expert opinion from a peer-reviewed article.The Sceptical Chymist (talk) 10:22, 23 October 2009 (UTC)

Personality changes

In a small minority of Prozac users, it has been noted by some psychiatrists that Prozac can transform a person's personality . This effect received substantial publicity in the early 1990's, when noted psychiatrist Peter D. Kramer coined the term, "cosmetic psychopharmacology." The idea being that we might use medication to improve work performance, redesign a person's personality, or improve resilience; and to make people more attractive, more energetic, or more socially acceptable . Peter Kramer's seminal book on the topic, Listening to Prozac, detailed the components of a person's personality that were transformed by Prozac:

• Risk-seeking; some users reported that their "moral sensibility" was gone, and their behavior was more risk-seeking than normal
• Compulsion; like all SSRIs, Prozac had significant effects on compulsive behavior and thoughts
• Pleasure Inhibition; instead of being though of as a pleasure pill, Kramer redefined Prozac's therapeutic efficacy by noting that Prozac restored one's capacity to feel pleasure
• Sluggishness of thought; good responders noticed an added dexterity in cognition, particularly in occupational and social settings
• Stress and sensitivity; interpersonal rejection sensitivity was transformed on Prozac, which led to increased psychological resilience
• Self-esteem; good responders noticed that not only did Prozac lift their moods, but it also made them feel good about themselves; a handful of users reported that while on the drug they felt more like themselves, but this effect quickly diminished while off of it.

Discontinuation syndrome

The section on discontinuation syndrom has been significantly expanded in this series of edits in January 2008 and this series of edits in January 2008. I have performed some relatively minor modifications to the section.

I have right now problem with the following two sentences:

"The double-blind controlled studies support this opinion. No increase in side effects was observed in several studies when the treatment with fluoxetine was blindly interrupted for a short time (4–8 days) and then reinstated, this result being consistent with its slow elimination from the body."

Namely:

• What opinion do the studies support? There are several statements in the article before the first quoted sentence, and it is unclear to which of these statement the statement "... support this opinion" refers.
• To what double-blind controlled studies does the first sentence refer?
• Both of the quoted sentences lack citations in spite of their speaking of studies; possibly they are implicitly cited in [35] - Fava M (2006), but that is not clear.

--Dan Polansky (talk) 13:00, 14 September 2010 (UTC)

Does this unsourced statement read like advertising?

Part of a recent addition:

...This mechanism is similiar to the one exhibited by the novel antidepressant Agomelatine which puts them both in the class of antidepressives refered to as NDDI's(Stahl). In the case of Fluoxetine the NDDI effect is assumely mediated only in the prefrontal cortex. This mechanism is also claimed to be responsible for the quick anti-depressive reponse the patient gain from it. Which can be as fast as an improvement from the day the patients starts taking it.

I was tempted to remove it as unsourced, but as a layman I'll leave that decision to the experts here. --CliffC (talk) 18:39, 30 November 2010 (UTC)

Edit Request: Mechanism of Action

1. Please cite references. Possible reference material: Zhang S, Li B, Lovatt D, Xu J, Song D, Goldman SA, Nedergaard M, Hertz L, Peng L. 5-HT2B receptors are expressed on astrocytes from brain and in culture and are a chronic target for all five conventional 'serotonin-specific reuptake inhibitors'. Neuron Glia Biol. 2010 May;6(2):113-25. Epub 2010 Sep 16. PubMed PMID: 20846463.

2. Mechanism of action of Fluoxetine as with all SSRIs (cited many times on Wikipedia) is unknown- but presumed. Please include this distinction in this article as well.Vp0rter (talk) 19:59, 27 January 2011 (UTC)

Can Prozac permanently alter your brain chemistry, wiring, or function, even after you quit?

I want to discontinue using Prozac and never again use ANY antidepressant.

Though I need to know something. Does Prozac permanently alter the way your brain functions, even after you quit taking it? I DON'T want my brain altered AT ALL. I WANT MYSELF TO BE THE EXACT SAME WAY I WAS BEFORE.

I am an Asperger's/Autistic person and I love my Asperger's/Autistic brain, though I was manipulated into taking the drug Prozac by a psychiatrist when I was younger and suffering from an illness thought to be psychological which wasn't psychological at all. And therefore I was desperate to accept anything.

But now I REALLY don't want it and I liked myself the way I was before. Am I permanently changed by the drug? I started taking it when I was 16 and now I'm 21. HELP please! — Preceding unsigned comment added by 71.161.249.253 (talk) 11:17, 14 June 2012 (UTC)

This is a talk page for discussing improvements to our article on Fluoxetine. It is not a forum for discussion of the drug, and in any case, we do not give medical advice on Wikipedia. Please ask your questions elsewhere. AndyTheGrump (talk) 12:32, 14 June 2012 (UTC)

It figures this is the kind of response I would get. I might as well go on Wiki Answers, where I'll get the response of "Duuuuuhhhhhhrrr i dont know but ill answer anyway!!!!! :)" or else have the question just fester there, unanswered. I suppose it wouldn't really make a difference, considering what I'd just received here.

Medical advice? What the hell kind of "medical advice" would this be? It just requires a straightforward answer based on facts. I'll be going to my psychiatrist on Monday (Which, by the way, happens to be June 18th, AUTISTIC PRIDE DAY!! Be sure to support it. I know I LOVE my AUTISTIC BRAIN!!). And either I've been screwed by the shrink or quitting will make my brain revert to the way it used to be. Either there's hope or I'm just left to rot.

I was hoping there would be someone here with a real sense of ethics, someone familiar enough with the effects of pharmaceutical drugs who could help me by answering a simple question. I mean, there has to be SOMEONE here with the expertise to help. It's just that they don't WANT to help me, even with the knowledge that they could very well do so within a matter of minutes.

I'm telling you I've been F**KED. So now YOU have to tell me what to do about it, as a decent human being. My creativity, my energy, my drive and focus and determination, I want it ALL back!! My unique and vivid perception of the world, I want it BACK!! That way I can expose the Pharmaceutical Industry for the crooks, liars, and frauds that they are! Psychiatrists are agents of the industry and they are criminals, child abusers and mind rapists.

First I need some help. I'm coming to you for help. This is an article pertaining to Fluoxetine. You're not saying that NOBODY here knows ANYTHING about the drug they're writing about, are you? I'm not asking about anything particularly dangerous, such as weaning myself off of meds. This I will do either on my own or with my psychiatrist's help. However, I think the long-term effects of Fluoxetine is an interesting question that people would want to know about. Perhaps information about it should be included within the article itself. — Preceding unsigned comment added by 71.161.249.253 (talk) 01:05, 15 June 2012 (UTC)

Bad Science

In the book Bad science : quacks, hacks, and big pharma flacks by Goldacre, Ben the author has a chapter about Fluoxetine, he claims Pfizer manipulated the clinical trial results to make it look like this drug is effective.

The author thinks differently.

As a result of reading this, I stopped taking the drug and noticed no difference in mood or anything else.

I'm inclined to agree with Goldacre. — Preceding unsigned comment added by 209.78.19.139 (talk) 04:41, 30 January 2013 (UTC)

This talk page is for discussions relating to improving the Wikipedia Fluoxetine article. It is not a forum for general discussions of the subject. AndyTheGrump (talk) 04:48, 30 January 2013 (UTC)

I think he has a point, I feel like shit now after taking Prozac. Cannabis is much better for dealing with western capitalism and it's effects on mental health than SSRI's. I strongly believe that the system as it is in western societies is a major factor in depression, suicide and mental health problems. But we can't talk about root causes can we? 149.241.185.241 (talk)

Violence and SSRIs

I deleted the additional comment about non statistically significant increases in violence being "alarming". The reason we analyze data with statistics is to measure the likelihood that the difference between treatment and control groups is due to chance. Thus using a non-statistically significant result as a counterpoint to multiple studies which showed a statistically significant reduction in violence upon treatment with fluoxetine and other SSRI's is inappropriate and undue weight.

David Healy's position, while getting a lot of attention from the mainstream media and anti-psychiatry activist groups, is not mainstream. Without the added material, this non-mainstream position is already accorded equal weight with the recommendations of the American Psychiatry Association, and the treatment guidelines of agencies such as the National Institute for Health and Clinical Excellence. It seems to me that this is more than a fair level of coverage. Alfred Bertheim (talk) 02:04, 27 February 2013 (UTC)

Removed citation for sexual side effects

I removed the citation "NTP_CERHR Expert Panel Report on Reproductive and Developmental Toxicity of fluoxetine" from the claims that "Similarly to other SSRIs, sexual side effects are common with fluoxetine; they include anorgasmia and reduced libido." I could not find decreased libido or anorgasmia anywhere in that reference. I added a citation needed marker in its place. 169.234.155.162 (talk) 04:09, 2 April 2013 (UTC)

John Virapen on German wikipedia

One information source, a radio talk show interview, led me to research drug company confessions of an insider that led me to the information on John Virapen's further information. Virapen is of India ancestry, was born in Guyana, moved to Europe when he was young to be educated in the medical field. Instead of a M.D. he got a PhD in psychology or similar such. He was recruited to become a marketing / sales person in the pharmaceutical industry. Google (patrick timpone radio one network) and the radio interview is listed from March 2013 or so. The interview from radio including advertising breaks is available as a .mp3 file.

Varapen's claims about prozac are contained within interviews, town hall talks, and several books that he wrote about the dirty deeds with which he was involved while working in the pharmaceutical industry. (1) One such item is that when a prior drug from the company development pipeline failed to be approved, next up was prozac. Eli Lilly & Co wanted prozac approved quickly (to replace revenues lost by the prior drug not being approved), so Varapen, working in Sweden at the time, determined from the key opinion maker players in that country what it would take to green light acceptance of the drug--answer: under the table cash payments and contract work awarded for clinical trials. (2) Varapen claims to have obtained letters (supposedly published on the Internet) from German officials who were quite negative on prozac, however, one year later, and the German government approved the drug. When Varapen asked Germans what new studies had been published that changed their minds, no responses were forthcoming.

Can this insider witness' confessions to "drug company wrong doing" be used in the article since he specifically identifies prozac as the focus of his key story? Oldspammer (talk) 17:47, 20 April 2013 (UTC)

No. Not without his claims being reported in credible independent reliable sources, for a start. AndyTheGrump (talk) 18:52, 20 April 2013 (UTC)

How is this drug synthesized?

Someone needs to post how this drug is synthesized. 2602:306:C518:6C40:505A:5C79:DCDB:627E (talk) 12:25, 26 May 2013 (UTC)

Unit for affinity ?

What's the unit for the affinities presented in the table? nM, I guess?

Good point, I will make that correction. Thanks, I missed that. Fuse809 (talk) 19:21, 24 November 2013 (UTC)

Should we indicate which AEs are irreversible/life-threatening with a symbol and the other types of AEs with other symbols?

Hi, people, I am writing to ask whether you's would accept it if I was to write a symbol, say † to indicate life-threatening/(usually) irreversible AEs like serotonin syndrome, tardive dyskinesias, etc. And other symbols (‡, #, ¤) to indicate other types of AEs, i.e. transient ones (e.g. nausea, vomiting), ones that may lead to permanent damage if it persists in the long-term (e.g. hypertension) and those that can, but usually are not irreversible. I will be editing the page to include this, if you object to it, feel free to change it back the way you like. Fuse809 (talk) 19:21, 24 November 2013 (UTC)

Wrong reference

Reference 41 is clearly wrong. Does anybody have the correct one?Ex-nimh-researcher (talk) 21:41, 22 October 2014 (UTC)

Looks like it was taken from the package insert. Could be my fault. Sometimes I use the Dberri citation tool for URLs and forget to change the "type" from PMID to URL, and get funny results like this as a result. Formerly 98 (talk) 22:50, 22 October 2014 (UTC)

Medical uses: PMDD (Premenstrual Dysphoric Disorder)

Suggest adding the following under the heading Medical Uses: Fluoxetine is also indicated in the treatment of PMDD, which is a severe form of PMS. Awesomeannay (talk) 06:53, 14 December 2014 (UTC)

References

Prozac as a personality modifier

don't know if this should be included in the new edit, but there is evidence to suggest prozac modifies personality. The problem being here that there is little quantifiable data measuring personality. to my knowledge there are no papers about this aspect but there have been a few books about it as well as anecdotal accounts from psychiatrists. i think this should be included due to the interesting issues it raises about personality and the underlying neural basis for it. It is also relevant in explaining prozac's widespread use even after the symptoms of depression have been curtailed. i can't remember the source, but i will put it up as soon as i find it in the library again.

any med perscribed to alter mood will either bring out your true personality or create another one. It's all dependant on how depressed someone is and why. if someone with bi-polar is giving an ssri it will get rid of there depression but make there mania more frequent and more intense. also seratonin isnt the only chemical in the brain that effects mood. but yes prozac is definatly personality modifying.... mood and personality are very related. also prozac takes a while before it takes any effects and those effects can range from off the walls manic to suicidal. and mixing ssri's with any other meds that in anyway effect serotonin can be dangerous. im on prozac for clinical depression. It helps alot with the depression but I can also notice a change in brain chemical lvls, it boosts both seratonin and dopamine, and it gives me a feeling similar to CNS stimulants where im very outgoing, analytical, want to fix things and help people, and become very talkitive.

---

Just my personal opinion, but I must say that prozac and other drugs just like it are way over-prescribed. While it is true that it does indeed have it's uses, I do not believe in diagnosing a 3rd grader with ADD and putting him/her on Prozac. To say the least, a 3rd grader is a child, and as such, has by very nature a short attention span, and is highly active. Instead of telling the parents to control their children like they should, the doctor will rescribe them prozac. You see, in a world where physical punishment is frowned upon ( I do not mean abuse! I would say a spanking is in order. I got spanked quite often when I messed up a child, and I turned out just fine, and there are millions like me)the kid is left with very little tangible consequences. He gets sent to his/her room, where they will most likely play video games, or call their friends to tell them what a drag their parents are. In retaliation, the parents send their children to a doc who will 9 out of 10 times, perscribe them prozac. Parents at that point no longer control their childrens erratic behaviour, but the drug does. Now fast forward to 10 yeard later. The child is sick of taking med's and wants to try life without them. I hate to say it people, but an addiction is an addiction. Every major depression they would have felt growing up was masked by the prozac, so they never really learned how to deal with the harshness of everyday life. Many of them will turn to other drugs to ease this feeling. This is wrong, and only happens because the parents failed to control their children. This in turn creates an even bigger problem when the child grows up, because they have no way to control their emotions. On the flip side, if someone is suffering from depression so bad, or they find that they cannot concentrate on the job at hand at all, then you call the doc, and should be given a drug like prozac. What it all comes down to, is people inability to cope with something. We all have problems coping from time to time, and from time to time, would be justified in something to take the edge off. But to constantly use it, even when it is not necessary, will only cloud things up worse. A lack of discipline is also a major factor. I welcome arguments to my point, and will check up regularly :-)—Preceding unsigned comment added by 204.194.77.3 (talk)

I agree they are over-perscribed. so are disorders like ADHD, Bi-Polar, and autism spectrum disorders. I wanna be a psychiatrist and I think that psychiatrists should try finding the root of problems like depression instead of just a quick chat and a perscription, I guarantee that 50% of people on anti-depressents just havnt figured out the root of the depression and all they need is therapy instead of medication, and medications arnt as safe and harmless on the body as people think. also I wish i could slap every pschiatrists who diagnosis kids with ADHD because a 7 year old is hyper and doesnt wanna listen to adults talking... its called be 7 years old.

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With respect to the content above, just a gentle reminder that this space is for the discussion of how to improve the Wikipedia article, rather than a general discussion forum of the topic. Many such forums exist elsewhere. Cheers. Awesomeannay (talk) 06:59, 14 December 2014 (UTC)

Pharmacodynamics: Neurosteroid modulation

Suggest adding that Fluoxetine acts not only as a selective serotonin reuptake inhibitor (SSRI), but also as a selective brain steroidogenic stimulant (SBSS), even at levels too low to affect serotonin reuptake . Specifically, it can stimulate the production of allopregnanonlone Awesomeannay (talk) 06:53, 14 December 2014 (UTC)

References

 Done - used 1 of the reviews you cited. Seppi333 (Insert 2¢ | Maintained) 08:30, 14 December 2014 (UTC)

Graphic

The 3D graphic under the line drawing should be reversed (flipped 180 degrees) so that it matches the line drawing. As it is represented now, they are reversed, and require the viewer to mentally flip one or the other. — Preceding unsigned comment added by 67.199.187.241 (talk) 14:29, 9 September 2015 (UTC)

Opening

The opening paragraph of the history section doesn't make much sense by itself, as it refers back to paragraph excised in change http://en.wikipedia.org/w/index.php?title=Fluoxetine&oldid=583132940. It is not clear why that paragraph was excided in the first place, it seems like a suitable degree of detail for this topic.

2607:FB90:2200:677F:DC1B:6E90:9A58:201A (talk) 14:03, 22 March 2015 (UTC)

As it is not a dif not sure to what you refer. Doc James (talk · contribs · email) 23:49, 22 March 2015 (UTC)

The diff would be with the version prior to the one shown. I have re-added a bit of (condensed) text from that version -- hopefully the story is clearer now. Thanks for pointing out the problem. Looie496 (talk) 15:17, 9 September 2015 (UTC)

WP:NOTCATALOG

"An article should not include product pricing or availability information unless there is a source and a justified reason for the mention. Encyclopedic significance may be indicated if mainstream media sources (not just product reviews) provide commentary on these details instead of just passing mention. Prices and product availability can vary widely from place to place and over time. Wikipedia is not a price comparison service to compare the prices of competing products, or the prices and availability of a single product from different vendors or retailers."

"Wikipedia articles are not:

• Simple listings without context information."

• "Directories, directory entries, electronic program guide, or a resource for conducting business. For example, an article on a broadcaster should not list upcoming events, current promotions, current schedules, etc., although mention of major events, promotions or historically significant program lists and schedules may be acceptable. Likewise an article on a business should not contain a list of all the company's patent filings.

73.162.132.47 (talk) 16:48, 17 October 2015 (UTC)

Sure so the question appears to be should we contain a list of brandnames for a product? If there are refs I do not see anything really wrong with it as long as they go low in the article and not the lead. Doc James (talk · contribs · email) 01:15, 18 October 2015 (UTC)

I just don't see what it really adds. Our article on automobiles doesn't contain a comprehensive list of every local brand of car made anywhere in the world. Nor do our articles on gasoline, televisions, oatmeal, epoxy glue, or personal computers. In the case of generic drugs, it is even less useful than in the above cases, because the generic must be EXACTLY identical to the original.

Honestly, do you ever read those tables of generic names? Do you get anything of value out of it? 2601:643:8100:8AF4:C4A2:D991:C7E0:9B17 (talk) 03:03, 18 October 2015 (UTC)

Fluoxetine for dysthymia

Is it a recommended drug for dysthymia?

Answer: It is what I was diagnosed with and I take it, so yeah I guess it is

Pregancy category C?

Several other reputable sites are reporting that Prozac has been classified category C. I've changed this page to reflect this data, although I was unable to personally verify.

Pedophilia

Nowhere in this article does it say this pharmaceutical drug is used to treat pedophilia.

Kapit

about this dif, the OR here is using a primary source and giving a bunch of WEIGHT to it, even quoting it. What we need is a reliable secondary source that gives significant weight to what Kapit said. Has nothing to do with what he said. Jytdog (talk) 19:45, 10 January 2016 (UTC)

You misrepresent OR. 2)I didn't introduce OR. What we need is for you to ground your objections with specific quotes from policy. Because you misrepresented OR. AGF is not a suicide pact. I don't think policy supports you so I'm restoring the user's content unless you can show otherwise. And I made three edits. J, you only attempted to justify your revert of one. There's no plausibly valid policy violation allegation here. --Elvey^(t•c) 20:50, 12 January 2016 (UTC)

WEIGHT needs to guided by the sources, and ideally secondary sources- this is what NPOV says. I'll acknowledge that it is me saying that doing otherwise is OR. Probably more importantly, providing long quotes from one side in a controversy just invites long quotes from the other side. What we do here is summarize controversies. Jytdog (talk) 22:11, 12 January 2016 (UTC)

• This seems pretty straightforward: primary sourcing is acceptable for uncontroversial material but Wikipedia policy and practice emphasises the use of reliable, independent secondary sources to establish the context of what any primary source might say and ensure we do not give undue weight to minority views, even if we might personally like them. So: secondary sources or it stays out. Guy (Help!) 11:44, 13 January 2016 (UTC)

Your statement that "we do not give undue weight to minority views" presupposes that the quote I added in which the FDA's (then) chief safety investigator, Dr. Richard Kapit, advocates an adverse side-effects black box warning expresses a minority view. You think it's a minority view? How so, since FDA DID mandate an adverse side-effects black box warning? When you say, "secondary sources or it stays out", you seem to be saying that primary sourcing of controversial material violates policy. I also note that you don't seem to care that Jytdog was misrepresenting OR; are you here with your editor or admin hat on? I think you are misrepresenting policy; you are implying that under Wikipedia policy, primary sourcing is unacceptable for controversial material, and that's simply false. Do you deny implying that, or are you willing to state for the record that you believe that under Wikipedia' OR policy, primary sourcing is unacceptable for controversial material? As far as what practice emphasizes: balanced enforcement of policies should be the rule, not the exception. Editors shouldn't selectively enforce policy in a way that favors views they personally like. --Elvey^(t•c) 19:11, 19 January 2016 (UTC)

Preposterous interpretation of WP:OR

For the record, this is what Jytdog removed, with the outrageous two-character edit summary explanation, "OR" ('dif' above): In contrast, in May 1985, FDA's (then) chief safety investigator, Dr. Richard Kapit, wrote: “Unlike traditional tricyclic antidepressants fluoxetine’s profile of adverse side effects more closely resembles that of a stimulant drug than one that causes sedation". He warned "It is fluoxetine’s particular profile of adverse side-effects which may perhaps, in the future give rise to the greatest clinical liabilities in the use of this medication to treat depression". In 1985 Dr. Kapit recommended "labeling warning [for] the physician that such signs and symptoms of depression may be exacerbated by this drug". No such warning was issued until 2004. --Elvey

References

Quick note. I dug up the document (on the website of a lawyer who sues drug companies) - it is here. Note Kapit's conclusion at the end:

Fluoxetine appears to be a relatively safe drug. If it can be demonstrated that treatment with fluoxetine significantly benefits patients with depression, it would appear that the benefits of treatment with fluoxetine would substantially outweigh the risks associated with this drug.

Certain clinical risks of mild to moderate severity did appear to be associated with the use of fluoxetine; as determined by a review of the safety data in this NDA submission. These potential risks include intensification of the vegetative signs and symptoms of depression, reduction of hemoglobin level, and elevation of serum LDH.

It is suggested that labelling be developed which advises physicians about possible exacerbations of the vegetative manifestations of depressive illness and about the possibility of decreases in hemoglobin. The occurrence of LDH elevations should be mentioned. If this drug is marketed, post-marketing studies should be required to assess more precisely the severity of these potential risks.

So not even close to the alarmist document that it was being made out to be. This is why we don't cherrypick primary sources. Cherrypicking is a form of OR, per WP:CHERRYPICK. That essay, btw, is listed as the first essay in WP:OR itself. anyway.... Jytdog (talk) 20:46, 19 January 2016 (UTC)

Serafem edits

The changes made to the page on Fluoxetine are all being done in the section entitled "History"; in this section we are adding a more detailed summary of the history of Sarafem and its use to treat PMDD. Since there is already a brief statement on Sarafem in the history summary, we are adding our edits to the section right there after the statement.

The sentence we follow with our history of Sarafem is as follows "Prozac was rebranded for the treatment of PMDD in an attempt to stem the post-patent decrease in Eli Lilly's sales of fluoxetine." This sentence itself we are editing to define what PMDD is, so instead it reads "Prozac was rebranded for the treatment of PMDD—premenstrual dysphoric disorder—in an attempt to stem the post-patent decrease in Eli Lilly's sales of fluoxetine."

Following this, there is a brief explanation of what PMDD is and its presence in the medical community. We then explain how Prozac was rebranded into Sarafem, causing the entire pharmaceutical industry to follow suit with their variations of Prozac. After this we talk about the marketing and media prescience pf Sarafem and the controversy it sparked. Such an influence caused a lot of response and in our last paragraph we explain the feminist response, as well as the significance it has on the feminist movement.— Preceding unsigned comment added by S.zayec (talk • contribs) 08:49, 16 March 2016 (UTC) S.zayec (talk) 02:11, 17 March 2016 (UTC)

Content added per above

I am moving this here as this appears to be WP:UNDUE to me. This is something that happens with student assignments at times; we need to pay mind to WEIGHT in the overall article, always.

PMDD was added to the widely used psychology manual called DSM in the early 1980s. This medicalization of the menstruation cycle stated that severe shifts in mood—along with common symptoms of PMS—that have had an affect on a woman’s personal life during the luteal cycle are means for PMDD diagnoses. With the backing of the medical community, the pharmaceutical company Eli Lilly & Co. was able to take Prozac, change its color, packaging and name to “Sarafem” to sell as the market’s only drug for PMDD. Following the release of Sarafem was a flood of marketing techniques that came from Eli Lilly & Co. to sell the drug. Eventually other pharmaceutical companies followed Lilly’s suit and did the same with their own version of Prozac, generic or not, to create their own version of Sarafem to sell.

The first commercial marketing Sarafem depicted a female struggling to release a grocery cart from a line of others and becoming increasingly frustrated and overwhelmed by the situation. As this is happening, a male voice over explains that while this woman thinks she is simply dealing with premenstrual symptoms, she is actually suffering from PMDD. This first commercial was soon removed from air after the Food and Drug Administration deemed it to undermine the seriousness of PMDD, which had already been receiving much criticism for not being a legitimate disorder. The advertisement had at the same time been criticized by feminist scholars, and the incident has since become a niche focus within feminist studies.

The modern development of PMDD, and the more recent creation of Sarafem, has been critiqued by feminist scholars as an industry that supports the spread of enlightened sexism in recent mass culture. Enlightened sexism is the name the modern feminist movement uses to describe a resurgence of female stereotypes based on the belief that women have already gained gender equality within western society. Sarafem and PMDD are thus considered relevant to enlightened sexism because, as supported by clinical psychologist Paula J. Caplan, it advertises to women who are simply experiencing PMS that they are mentally ill and need to seek uneeded medical treatment. Other researchers such as Renay Tannar have labeled PMDD and PMS as socially constructed illnesses, meaning mock illnesses simply created by a patriarchal society in order to continue to oppress women. Past feminist critiques of the medication and illness have rested on the belief that, when women believe they have a mental illness related to the menstrual cycle, this perpetuates stigma surrounding womanhood and isolating women from positions of power in societal structures due to the belief that their nature is so different than that of men's. Such discourse has caused Sarafem, or any use of fluoxetine as a treatment for PMDD, to maintain it's controversial status as a therapeutic drug

References

-- Jytdog (talk) 03:52, 25 March 2016 (UTC)

selective brain steroidogenic stimulant

Away back in 2014, here, someone suggested adding content about a putative "selective brain steroidogenic stimulant" effect, and it was done. I just looked into pubmed on this, and there are four reviews on this -- all from the same person. This appears to be a "pet theory" and not accepted knowledge, so I am moving this out of all the statements of facts part of this article and moving it into the Research section. Jytdog (talk) 22:20, 1 April 2016 (UTC)

done here. Jytdog (talk) 22:29, 1 April 2016 (UTC)

I understand these edits, Seppi, but I struggle with elevating this one lab's pet theory to fact. The only four reviews are by him; this notion of SBSS is not getting taken up and in my view it isn't appropriate for WP to elevate it. I'm OK with keeping the biochemical stuff in the PD section if we remove the SBSS terminology. is that OK? Jytdog (talk) 06:23, 2 April 2016 (UTC)

I looked at the revision history before seeing your talk page post. Given your argument, I decided to delete the content relating the pharmacodynamic effect to a clinical effect; I retained the SBSS terminology because it's technically an accurate description of the pharmacodynamic effect, but I dont really care if we delete that. Seppi333 (Insert 2¢) 07:24, 2 April 2016 (UTC)

well, putative PD effect. Even that is seems to just be coming out of his lab. but i can live with this - the claiming of a new class of anti-depressants is a a bit too much for WP at this point in time. Thanks. Jytdog (talk) 07:37, 2 April 2016 (UTC)

Feminism and Serafem

About this content:

Critiques of Sarafem'

The modern development of PMDD, and the more recent creation of Sarafem, has been critiqued by feminist scholars as an industry that supports the spread of enlightened sexism in recent mass culture. Some critiques about Sarafem, as supported by clinical psychologist Paula J. Caplan, are that it advertises to women who are simply experiencing PMS that they are mentally ill and need to seek unneeded medical treatment. Other researchers such as Renay Tannar have labeled PMDD and PMS as socially constructed illnesses. Such discourse has caused Sarafem, or any use of fluoxetine as a treatment for PMDD, to maintain a controversial status as a therapeutic drug.

References

I struggle with this for a few reasons. first, it is not in dialogue with the rest of the article, which touches on this topic. This seems to perhaps be a class assignment? Secondly, it portrays "feminists" as speaking with one voice on this issue and actually does the typical male/sexist maneuver of taking one or two examples and claiming that they represent Reality. Third it presents only one side of what it calls a "controversy". But see

• here, for example, is an article written by an MD who is a woman, who describes the condition as a condition.
• PMID 12132631 was written by a female nurse, and actually does a pretty good job of laying out the hype and the reality (and makes it clear that at of 2002, there were women who actually have PMDD, rigorously speaking).
• PMID 26351143 is a more recent review that also lays out the spectrum between hype and reality.

Giving my own opinion here. I find it kind of sexist that just because a person is born with a uterus and has to suffer periods their whole life that there should be no medicine to help deal with that. Its almost as sexist as the notion that women should be forced to pay for contraceptives while men get Viagra paid for or that abortions should be illegal. Really? Women should just be determined by their biology and the medical establishment should do nothing? Is biology really destiny for women? This content is pretty radically POV and it cannot stand as it is.

That said i see the point of the critique - namely the male-driven establishment painting women as hysterical and medicating them. That is a voice. But this content is not OK. Jytdog (talk) 23:41, 18 April 2016 (UTC)

External links modified

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Fisher

Nothing about Carrie Fisher? I feel as though this would be a good thing to put in this. -A lad insane (Channel 2) 18:23, 10 January 2017 (UTC)

WP:NOTGOSSIP Jytdog (talk) 23:28, 10 January 2017 (UTC)

If you're talking about number 3, it's actually mentioned in her article, so that would not be consistently applied in that case. However, I will admit this is a relatively trivial piece of information, so maybe not. -A lad insane (Channel 2) 02:15, 11 January 2017 (UTC)

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Expanding society and culture

It should probably be mentioned that, for better or worse, fluoxetine (specifically as "Prozac") is one of the drugs most associated with the term "antidepressant" in American culture, and it often figures both in praise and criticism of antidepressants. I have definitely read that Carrie Fisher asked to be buried in a big Prozac capsule and that this wish was granted. But I'm not personally adding all of this to the article because I am not currently willing to track down sources to back this up. I may do so later, or someone else can feel free to. I also think it's worth getting a more worldwide perspective than the one I am currently writing about. Finsternish (talk) 08:15, 2 March 2018 (UTC) In many ways Prozac is to antidepressants as Valium is to anxiolytics. Finsternish (talk) 08:17, 2 March 2018 (UTC)

Given its ubiquity as the default antidepressant in American culture, this is a good idea. I'll get around tuit. kencf0618 (talk) 05:19, 13 September 2018 (UTC)

Suicide and Fluoxetine

There isn't much evidence that fluoxetine reduces suicide risk. It may increase suicide risk in younger patients. I removed the statement in the lede about possible reduction of suicide risk in people older than 65, as this is not supported by the given citation, contradicts info in the main body of the article. There really isn't much evidence specifically about whether fluoxetine increases or decreases risk of suicide in younger persons or older persons. A more nuanced discussion of this would be good for the main body of the article. I've added one meta-analysis and statement to the depression section. Perhaps there ought to be a suicide section for the fluoxetine page?Sbelknap (talk) 06:25, 24 December 2018 (UTC)

Yup it may be that increaases suicide in young people but decreases it in older people. We mention both. There IS a suicide section Fluoxetine#Suicide? Doc James (talk · contribs · email) 02:05, 25 December 2018 (UTC)

QT Prolongation

Fluoxetine can cause QT prolongation:

https://en.wikipedia.org/wiki/Drug-induced_QT_prolongation

As this is potentially fatal adverse effect, it should be probably mentioned directly on Fluoxetine Wikipedia page.

195.113.111.28 (talk) 13:02, 2 September 2019 (UTC)

I have added a section detailing the conditional risk of QT prolongation associated with fluoxetine use. PeaBrainC (talk) 14:45, 2 September 2019 (UTC)

Violence

Are there any side-effects, related to violence, that are peculiar to Fluoxetine and not just to all SSRIs in general? Thanks. Martinevans123 (talk) 14:12, 26 March 2021 (UTC)

Fluoxetine is different from other SSRIs. It is the only SSRI that works in children and, in addition, unlike other SSRIs, it does not make them more aggressive and unruly (the scientific word "disinhibited"). So, it looks plausible that fluoxetine, unlike other SSRIs, may have some positive effects on violence.The Sceptical Chymist (talk) 15:34, 26 March 2021 (UTC)

Well, if that is so, and good MEDR secondary sources could be found, this could be added to the article. I think the general effects of SSRI's on "disinhibition" should be dealt with at Selective serotonin reuptake inhibitor, although I guess we could have a note here directing the reader to that section. Martinevans123 (talk) 16:09, 26 March 2021 (UTC)

I disagree in principle with that reasoning. You are arguing that the page Fluoxetine should _only_ contain information specific to fluoxetine, and delete _all_ information which is also true for all SSRIs. Applying again that principle, than the page SSRI should not contain any info that is true for all Antidepressants, and so on. That doesn't seem reasonable at all. It would also imply deleting most of the article as it is currently. AndreaGMonaco (talk) 15:57, 1 April 2021 (UTC)

Hmm, I hadn't thought of that. But now you mention it, that would be a very good way of eliminating overlap and duplication. Martinevans123 (talk) 15:59, 1 April 2021 (UTC)

My example was paradoxical. That policy is not usually applied in Wikipedia, and it wouldn't be wise to do so. Think for example about animals, another field with a rich taxonomy: the page Dog would not contain anything which is also true for other or all Canis, which would not contain anything which is also true for other or all Canina et cetera. That seems artificial and unreasonable, and would be a major departure from current status. The average person who visits the page Fluoxetine probably expects both kind of information, that specific to Fluoxetine and that which is also true for some broader set, and it's reasonable to provide that. Also, often it's not easy to separate the two. AndreaGMonaco (talk) 17:22, 1 April 2021 (UTC)

Other canines exist. We're here to discuss Fluoxetine. But WP is rife with duplication. It's really not needed in an electronic encyclopaedia - after all, we have hyperlinks, don't we. Martinevans123 (talk) 17:46, 1 April 2021 (UTC)

It is really simple: if a statement is true for fluoxetine based on reliable sources and is notable enough to include - it goes in. The Sceptical Chymist (talk) 20:15, 1 April 2021 (UTC)

Suicide

Here is what the subchapter on suicide specific to fluoxetine in this article states: "Considered separately, fluoxetine use in children increased the odds of suicidality by 50%,[61] and in adults decreased the odds of suicidality by approximately 30%.[58][59] Similarly, the analysis conducted by the UK MHRA found a 50% increase of odds of suicide-related events, not reaching statistical significance, in children and adolescents on fluoxetine as compared to ones on placebo. According to the MHRA data, for adults fluoxetine did not change the rate of self-harm and statistically significantly decreased suicidal ideation by 50%.[62][63]" It has to be summarized accordingly in the lead. The Sceptical Chymist (talk) 11:56, 2 April 2021 (UTC)

Prozac Mortal Effects Coverup

There are articles about Eli Lilly, that they knew about its dangers, but they forced their scientists to cover it up. https://ahrp.org/prozac-revisited-concerns-about-suicides-surface-boston-globe/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC539828/ Because there were making tons of money! Furthermore they tried to discredit scientific studies about dangers of Prozac, which claim it cause serious side-effects, seems familiar? It scares me, that there is not more info! Even at current time psychiatrists still promote SSRIs, which are unhealthy, even serotonin imbalance theory was refuted: https://bigthink.com/surprising-science/antidepressants-withdrawal?rebelltitem=3#rebelltitem3 While no one still know how they work... Empleat (talk) 18:34, 7 April 2021 (UTC)

Fluoxetine side effects

I have been taking fluoxetine for almost 3months & the last few days have been light headed & wouldn’t want to chance driving.By evening it wears off. I intend to contact doctor but would appreciate any advice. 2.30.230.136 (talk) 11:31, 3 February 2022 (UTC)

Sorry, Wikipedia cannot give any medical advice. The doctor who prescribed your medication is your very best route. Otherwise, suggest you try a chat group or notice-board site that specialises in medication or health issues. Thanks. Martinevans123 (talk) 11:46, 3 February 2022 (UTC)

Neuroprotectivity

Thinking we should consider adding a section on (or at the very least, a reference to) the neuroprotective/neurogenic mechanisms that underpin the use case of Fluoxetine in patients with OCD pathologies. I recommend drawing from;

1. Kroeze, Y et al. “Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus.” Translational psychiatry vol. 5,9 e642. 22 Sep. 2015, doi:10.1038/tp.2015.145

-- which ties together the existing body of literature pretty nicely. One of the main underlying pathways appears to be the upregulation of genes responsible for controlling myelination. A really nice summarization from this paper reads,

"Moreover, in obsessive compulsive disorder patients, abnormalities of myelin integrity have been found that were partially reversed by SSRI treatment. Taken together, these findings suggest that myelination is dysregulated in several psychiatric disorders and can be regulated by antidepressants, like fluoxetine." 

I'd suggest this quote, in particular, because of the relatively plain language used by the authors here. If the proposed addendum ends up needing more support, I've included a few more sources below.

---

2. Pittenger C, Bloch MH. Pharmacological treatment of obsessive-compulsive disorder. Psychiatr Clin North Am 2014; 37: 375–391. [PMC free article] [PubMed] [Google Scholar]

3. Alme MN, Wibrand K, Dagestad G, Bramham CR. Chronic fluoxetine treatment induces brain region-specific upregulation of genes associated with BDNF-induced long-term potentiation. Neural Plast 2007; 2007: 26496. [PMC free article] [PubMed] [Google Scholar]

4. Fan Q, Yan X, Wang J, Chen Y, Wang X, Li C et al. Abnormalities of white matter microstructure in unmedicated obsessive-compulsive disorder and changes after medication. PLoS One 2012; 7: e35889. [PMC free article] [PubMed] [Google Scholar]

5. Malberg JE, Eisch AJ, Nestler EJ, Duman RS. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 2000; 20: 9104–9110. [PMC free article] [PubMed] [Google Scholar]

6. Yune TY, Lee JY, Kang S. Fluoxetine prevents oligodendrocyte cell death by inhibiting microglia activation after spinal cord injury. J Neurotrauma 2015; 32: 633–644. [PMC free article] [PubMed] [Google Scholar]

 Atomic putty? Rien!  16:48, 13 January 2023 (UTC)

Decided to be bold. Added a sentence to the mechanism of action. Tried to summarize as best as possible. ^-^ Atomic putty? Rien! 17:11, 13 January 2023 (UTC)

Pediatric restoration reversion

@SandyGeorgia Apologies as I am quite new to wikipedia, but familiar with antidepressant research and it's unclear to me why the edit regarding the restoration of pediatric fluoxetine trials was reverted. In this case a primary source is relevant and necessary. Clinical trial restorations are not often going to be found in a review, and they're not going to be making it to other secondary sources unless there's some sort of gross misconduct that results in scandal à la Study 329. In this case the authors' editorializing is not even particularly necessary, in looking at the CSR data it is obvious that there was misreporting to the extent that the studies, which were subsequently included in the meta-analyses above, cannot be relied upon. In any case, to describe them as "questioned" downplays the issue quite a bit. Perhaps a disclamatory sentence is suitable: "According to a 2022 restoration, the studies....were flawed and misreported." Feline negativity (talk) 19:22, 21 January 2023 (UTC)

It wasn't reverted; it was reworded.[1] Since it's not a secondary review, we can't state it as fact in Wikivoice. It's only someone's opinion, and it's unclear if it belongs in the article at all. I gave it the benefit of the doubt by merely tagging it. Looking at the underlying data and making our own conclusions about them is original research. SandyGeorgia (Talk) 19:40, 21 January 2023 (UTC)

@SandyGeorgia The first point is fair, my bad, and as I suggested the point could be reworded. To describe a clinical trial restoration as "only someone's opinion" borders on the absurd. The meta-analyses and systematic reviews regarding the efficacy of fluoxetine in childhood depression rely on only a few trials, two of which are the ones that have been restored. If the results from these trials might be significantly flawed it is obviously deserving of mention. Wikipedia policies seem to me to indicate that where it is relevant and necessary, and in the absence of secondary literature, a credible primary source may be used. Feline negativity (talk) 20:22, 21 January 2023 (UTC)

There are times when we can carefully, very carefully use primary sources (although less so in biomedical content). Whether this is one of those times is a matter for consensus, which is why I reworded and tagged rather than removed the content. Whether you can find a way to re-word within policy, I can't say (I am iPad editing from the car on a hotspot and not home to do research now), but your justification above involves mostly original research. I'd suggest asking for help on how to appropriately word the content you want at WT:MED, where others might be able to engage and help out here more quickly and ably than I can right now. I'll put a query there next ... SandyGeorgia (Talk) 21:17, 21 January 2023 (UTC)

Done, SandyGeorgia (Talk) 21:52, 21 January 2023 (UTC)

If I'm parsing the abstract correctly (alas I can't access the full text), this seems to be a review of two separate placebo-controlled trials that were conducted by Eli Lilly and Company between 1991 and 1995, and 1998 and 1999 respectively. The authors of the 2022 paper; Gøtzsche and Healy, do not appear to be connected with either of the two studies, and it looks like Gøtzsche has been working on this since circa May 2019.

Though I do not have the full text to confirm, I would query if this is actually primary research given that on the surface it does not look like the authors have conducted the underlying clinical trials which they are reviewing some 23-27 years after the fact. I'll stick in a request at WP:REREQ shortly to see if I can get the full text of this to check further. Sideswipe9th (talk) 23:01, 21 January 2023 (UTC)

@Sideswipe9th the full text is available on Gøtzsche's website: https://www.scientificfreedom.dk/wp-content/uploads/2022/11/2022-Gotzsche-restoration-of-the-two-fluoxetine-trials-in-children.pdf Feline negativity (talk) 23:06, 21 January 2023 (UTC)

Oh perfect! I will give that a read now! Sideswipe9th (talk) 23:06, 21 January 2023 (UTC)

Thanks for pitching in, Sideswipe9th. You can see from this that PubMed does not consider it a review. Bon courage knows more about how to use that tool, but this is what a review string looks like. I believe that when PubMed fails to classify something that says it's a review as one, there's usually a good reason, but Bon courage will know better. SandyGeorgia (Talk) 23:59, 21 January 2023 (UTC)

PS, you might also want to go ahead and get the actual source, as we can't be certain that the self-published version is the same as what was printed. SandyGeorgia (Talk) 00:02, 22 January 2023 (UTC)

Ok. Some questions coming up as I'm reading that would impact on the prose we can write:

• Were the X065 and HCJE trials the only two blinded-control trials done as part of the approval process for fluoxetine in children and adolescents?
• How well regarded and how impactful is the journal (International Journal of Risk and Safety in Medicine) Gøtzsche's paper was published in?
• On page 19, Gøtzsche states A meta-analysis of 24 placebo-controlled trials in over 4400 children and adolescents showed that for every 1000 patients treated with drug instead of placebo, there were 14 additional cases of suicidality, but doesn't cite a source for this in the relevant passage of the text. Do we know what meta-analysis he's referring to? This seems as though it would also be useful for our content.

Having read through this paper now, it does appear to meet the definition of a systematic review, which would put it pretty high on our MEDRS pyramid. It's clear as to which control trials it is analysing, and how the authors reached their conclusions based upon the data available within those trials. It does diverge quite significantly from the original reporting of the trials by Eli Lilly, as a result is is very critical of how those trials were conducted and their results presented at the time, and the authors point out that it does have some limitations due to missing data within the control trial reports that was either omitted, unrecorded, or censored. I would be somewhat wary of relying solely on PubMed's metadata in determining whether or not this is a review, as metadata can be incorrect, but I would be interested in hearing what Bon courage thinks in relation to this. I've also now received the version of the paper that was published in the journal from REREQ, I'll do a diff on them shortly, but at first glance they do appear to match up closely.

Dependent on the questions above, and what Bon courage says about the metadata, I think there is a better way to phrase the sentence for this source in the article. Something like A 2022 systematic review of [two of the/the two?] original blinded-control trials used for approval of fluoxetine use in children and adolescents with depression found that both of the control trials were severely flawed, and did not demonstrate the efficacy of the medication. where the text in brackets is determined by the answer to my question above on X065 and HCJE. Sideswipe9th (talk) 00:26, 22 January 2023 (UTC)

Quick note to say I've done a diff between the file linked above, and the one I received from REREQ which was acquired directly from the journal, both files are identical. Sideswipe9th (talk) 00:36, 22 January 2023 (UTC)

a) So far as I can tell, yes, they are the only two mentioned here.

b) Journal would seem to be reputable, editorial board has a number of prominent pharmacovigilance experts and the publisher isn't on Beall's list.

c) It was difficult to find a published study on this. A couple papers and the FDA website itself mention an FDA-commissioned meta-analysis matching that description. Eventually I found this, whose numbers differ slightly from other reports but is probably the final, published version of the meta-analysis.

Will incorporate your suggested sentence. Feline negativity (talk) 08:39, 22 January 2023 (UTC)

I could find nothing indicating concern about the journal, but it would be nice if International Journal of Risk and Safety in Medicine would be not-RED. SandyGeorgia (Talk) 12:08, 22 January 2023 (UTC)

Scopus says that it's a mid-tier journal.[2] That's good enough. WhatamIdoing (talk) 17:30, 22 January 2023 (UTC)

When PubMed lists a paper as a review, we can usually rely on that, but when it doesn't say anything, that doesn't mean that it's not a review. In particular, it can take a couple of months for this information to appear in PubMed. Also, reviews frequently weren't marked as such in the previous century.

However, in the case of https://pubmed.ncbi.nlm.nih.gov/35786661/ (scroll down to the "Publication types" section), PubMed (now) says this paper is a systematic review. WhatamIdoing (talk) 04:51, 22 January 2023 (UTC)

That solves that then, thanks WAID and Sideswipe9th for the help here. Feline negativity depending on how you want to handle the bracketed portion in Sideswipe's proposed text above, I will leave the honors of rewriting/re-inserting to you. My sincere apologies for the extra work, but I hope we ended with a solid and better result. SandyGeorgia (Talk) 05:52, 22 January 2023 (UTC)

Chemical vs Medical Toxicity of Fluoxetine

Someone keeps expunging the fact that the NIH has determined that fluoxetine is an acutely toxic drug.

https://pubchem.ncbi.nlm.nih.gov/compound/fluoxetine

They revert the page as soon as I make the edit.

I request Wikipedia ban the culprit, come to a compromise (which must include this source), or I will quit the platform in protest. 2601:6C5:300:B230:B4C2:F17D:A842:B895 (talk) 01:03, 31 January 2023 (UTC)

Yeah, it is potentially toxic, if taken in large enough quantities - far beyond prescribed dosages. As are pretty well all pharmaceuticals, if you exceed the recommended dosage by enough. Along with more or less every other substance known to humankind. Don't let the door hit you on the way out... AndyTheGrump (talk) 01:23, 31 January 2023 (UTC)

That's a false equivalence fallacy.

The NIH does not designate drugs as "acute toxic" with a skull and cross bones for nothing. It doesn't mean "only if you ingest a large amount."

You are censoring. 2601:6C5:300:B230:B4C2:F17D:A842:B895 (talk) 02:12, 31 January 2023 (UTC)

The person deleting the citation to fluoxetine's toxicity is also exhibiting disrespectful conduct, in violation of Wikipedia rules, i.e. "Don't let the door hit you on the way out..."

I didn't point out that this person ostensibly cannot write English in complete sentences. 2601:6C5:300:B230:B4C2:F17D:A842:B895 (talk) 02:20, 31 January 2023 (UTC)

Wikipedia cannot allow editors to delete highly authoritative, unbiased, and verifiable sources and citations simply because it is inexpedient, may cause law suits, a decline in drug's sales/revenue, or for any other reason. The NIH is one of the most authoritative sources available.

If the person deleting the citation doesn't want to take it seriously, then that's his prerogative, but it is not his prerogative to impose his interpretations and opinions of the source/citation on everybody else by deleting it.

I recommend that Wikipedia ban this editor due to his ignorance, censorship, and abusive behavior. 2601:6C5:300:B230:B4C2:F17D:A842:B895 (talk) 02:30, 31 January 2023 (UTC)

If you wish to seek the inclusion of a content relating to the toxicity of fluoxetine, then you must first provide MEDRS compliant sources that support the content you wish to add. That content must first be added to the article's body, in a manner that complies with core content policies like WP:NPOV, WP:V, and WP:NOR. Then, if it can be further demonstrated via through the weight of reliable medical sources that the toxicity of fluoxetine is a significant topic within fluoxetine research, it can be considered for adding into the lead. A medication's entry on PubChem is not MEDRS compliant, nor is it a peer-reviewed systematic review of of the relevant literature on that medication. Sideswipe9th (talk) 02:39, 31 January 2023 (UTC)

Thanks.

1) Could you support your conclusion that fluoxetine is not MEDRS compliant? I did not observe any mention of PubChem in MEDRS.

2) Furthermore, could you support your conclusion that a citation must satisfy the requirement of constituting a "peer-reviewed systematic review of [] the relevant literature." If that's the standard, almost all citations would need to be expunged. 2601:6C5:300:B230:B4C2:F17D:A842:B895 (talk) 03:13, 31 January 2023 (UTC)

I did not say that "fluoxetine is not MEDRS compliant". I said that a medication's entry on PubChem is not MEDRS compliant. Fluoxetine has had many published papers on it that meet the criteria of MEDRS, and are cited in the article.

I did not say that all citations must be peer-reviewed systematic reviews. That remark was in reference to the text you inserted, which read The National Institute of Health has determined through a comprehensive review of the medical literature that Fluoxetine is an accutely toxic drug. Though I recognised I could have been clearer in saying that. In order to state your proposed sentence, in that form, in wikivoice, it would need to be cited to a peer-reviewed systematic review of the literature on fluoxetine that states that fact. A medication's entry on PubChem does not meet those requirements. Sideswipe9th (talk) 03:21, 31 January 2023 (UTC)

With respect to the first sentence, I think you understood the idea I was conveying, and are not being entirely intellectually honest. With respect to the second, I wrote an e-mail to NIH for clarification. In the meantime, I'm assuming that NIH conducted a diligent review before characterizing the drug as "acute toxic." I will report more when I receive their reply concerning its review standards and methodology.

Would it be amenable to all those objecting simply to insert a sentence that reads:

"According to PubChem's entry for Fluoxetine, Fluoxetine is identified with an acute toxic 'skull and cross bones' and 'health hazard' pictograms, among others."

That's simply stating a fact without drawing any toxicological conclusions. 2601:6C5:300:B230:B4C2:F17D:A842:B895 (talk) 03:35, 31 January 2023 (UTC)

No. AndyTheGrump (talk) 03:39, 31 January 2023 (UTC)

No. That still has the same problem with PubChem being non-MEDRS. Sideswipe9th (talk) 03:47, 31 January 2023 (UTC)

That's censorship. Why not let people decide for themselves without Wikipedia arrogating the authority to decide for them? Just point out that it isn't peer reviewed, if that's correct.

How about:

1) Fluoxetine disrupts sleep architecture, specifically decreasing sleep continuity and slow wave sleep. Wichniak, Adam, Aleksandra Wierzbicka, and Wojciech Jernajczyk. "Sleep and antidepressant treatment." Current Pharmaceutical Design 18.36 (2012): 5802-5817.

2) Fluoxetine, by decreasing slow wave sleep, impairs the ability of the brain to wash away amyloid beta and other toxic material via the glymphatic system.

"In the deepest sleep phases, cerebrospinal fluid rushes through the brain, sweeping away beta-amyloid protein linked to brain cell damage. Without a good night’s sleep, this housecleaning process is less thorough, allowing the protein to accumulate—and inflamma­tion to develop. Then, a vicious cycle sets in. Beta-amy­loid buildup in the brain’s frontal lobe starts to impair deeper, non-REM slow-wave sleep. This damage makes it harder both to sleep and to retain and consolidate memories." https://www.health.harvard.edu/sleep/how-sleep-deprivation-can-cause-inflammation

3) Fluoxetine and its major metabolite, norfluoxetine, potentiate 5HT2C, which activates the central nucleus in the Basal Lateral Amygdala. This activity potentiates neuropathic pain as well as emotional-affective and anxiety- and depression-like behaviors. Ji, Guangchen, et al. "5-HT2C receptor knockdown in the amygdala inhibits neuropathic-pain-related plasticity and behaviors." Journal of Neuroscience 37.6 (2017): 1378-1393. 2601:6C5:300:B230:B4C2:F17D:A842:B895 (talk) 04:27, 31 January 2023 (UTC)

According to its site:

"Where does the data in PubChem come from? PubChem records are contributed by hundreds of data sources. Examples include: government agencies, chemical vendors, journal publishers, and more."

It appears like the data from which NIH bases its pictograms is more reliable and diverse than many if not all MEDRS-approved ones.

I will wait until they respond, but your position for the moment appears untenable. 2601:6C5:300:B230:B4C2:F17D:A842:B895 (talk) 05:45, 31 January 2023 (UTC)

@2601:6C5:300:B230:B4C2:F17D:A842:B895 I think it's unlikely you'll get a reply from the National Institutes of Health. However, the safety data on PubChem regards industrial production and laboratory use. It's a basic principle of toxicology that the dose makes the poison. Many drugs used throughout medicine can be acutely toxic in large doses, as you can see on PubChem by searching other common drugs. However, at clinical doses they will not pose health hazards. The same goes for fluoxetine. Certainly there are legitimate concerns about its medical use, as with other SSRIs, such as suicidality or withdrawals, but if fluoxetine were acutely toxic at the doses used in clinical practice it would have been noticed by now. Feline negativity (talk) 06:28, 1 February 2023 (UTC)

Re: "[I]f fluoxetine were acutely toxic at the doses used in clinical practice it would have been noticed by now."

The hepatotoxicity of fluoxetine has been widely observed. "Fluoxetine-induced liver damage is a cause of chronic liver disease." Karimi-Khouzani, O., Heidarian, E. & Amini, S.A. Anti-inflammatory and ameliorative effects of gallic acid on fluoxetine-induced oxidative stress and liver damage in rats. Pharmacol. Rep 69, 830–835 (2017).

Fluoxetine has a logP of 4, meaning it is highly lipophilic, as is its major metabolite, norfluoxetine which exhibits a logP of 3.5. Drugs that are highly lipophillic, and which are extensively metabolized by the liver, are often markedly hepatotoxic. In addition both fluoxetine and norfluoxetine have a very long half lives (4-6 days with chronic use), causing bioaccumulation over time. As a result, the dose is nort commensurate with blood concentration levels or liver burden when taken chronically consistent with clinical use.

With chronic use (12 weeks or more, which is usually required to putatively observe therapeutic effect), the concentration levels could violate Chen's rule of two, even though the dose of the drug would not meet the criteria. The reason is that Chen's rule of Two is ostensibly predicated on the assumption that the drug's half-life is several hours rather than several days.

Even though you may argue that this is evidence of non-acute toxicity, this is not the case. Toxicity in vivo takes longer to manifest than in vitro studies such as HepG2 would disclose. The liver is a fairly resilient organ, which means that often even acutely toxic drugs will not cause liver failure immediately. It would manifest slowly but progressively faster as the integrity of liver becomes increasingly damaged and functionally compromised. 2601:6C5:300:B230:2491:9990:879F:14A5 (talk) 04:41, 12 February 2023 (UTC)

The main point is the first point - about any chemical being toxic if taken in large enough quantities. This article is about fluoxetine as a 'drug', not about fluoxetine as a laboratory 'chemical'. Making statements about its chemical toxicity would mislead the public. All the conversation about whether PubChem is MEDRS is a red herring for the purposes of this discussion. Even if PubChem were MEDRS (and it might be), the PubChem assignment of chemical toxicity would not support a statement in this article that fluoxetine is toxic. Jaredroach (talk) 18:11, 5 February 2023 (UTC)

Also: there is a link to the PubChem entry in the article. So any reader can click on the link to get the details (almost all of which are minutiae that don't belong in the article) of toxicity and all the other PubChem stuff. So calls of "censorship" are overblown. Wait until someone deletes the link to PubChem before indicting that person for censorship. Jaredroach (talk) 18:18, 5 February 2023 (UTC)

Re: "The main point is the first point - about any chemical being toxic if taken in large enough quantities."

I've already addressed this. This is a false equivalence fallacy.

The pertinent inquiry is whether Fluoxetine is acutely toxic at the doses that the FDA and other regulatory bodies across the world have approved the drug. As I state in my response to Feline negativity, fluoxetine is acutely toxic to the liver in doses approved by the FDA and other regulatory agencies.

Re: "This article is about fluoxetine as a 'drug', not about fluoxetine as a laboratory 'chemical'. Making statements about its chemical toxicity would mislead the public."

All drugs are chemicals so this is a false dichotomy. Indeed, if fluoxetine is deemed to be acutely toxic in the lab, those dealing with the drug would be required to wear protective gear when handling the drug. Ingesting the drug would expose an individual to substantially greater harm, so you are arguing against yourself. Indeed, failing to inform the public of fluoxetine's toxicity through this platform, employing spurious reasoning, obfuscation and pretext, would constitute lying through omission.

RE: "All the conversation about whether PubChem is MEDRS is a red herring for the purposes of this discussion. Even if PubChem were MEDRS (and it might be), the PubChem assignment of chemical toxicity would not support a statement in this article that fluoxetine is toxic."

This first sentence is an example of a type of projection. The comment that Pubchem's identification of fluoxetine's acute toxicity is a red herring is itself a red herring. The drug is acutely toxic to the liver, if not other organs as well. I suspect the editor knows that PubChem is MEDRS (it is) <https://en.wikipedia.org/wiki/Wikipedia:Reliable_sources/Noticeboard/Archive_306#Question_about_PubChem_%2C_Sigma_Aldrich_and_ChemSpider>).

The editor knows that he's won't "win" by stating that is not, so instead attacks the relevance of MEDRS. The purpose of MEDRS is precisely the opposite of what the editor claims. It is meant to verify reliable and pertinent sources. PubChem is MEDRS and reliable, which is consistent with the vast body of reliable research papers and other sources it collects.

According to a PubChem representative, PubChem is part of the "National Library of Medicine." The representative stated as follows: "We report data from high quality sources and list the source as the reference with their data."

RE: "Also: there is a link to the PubChem entry in the article. So any reader can click on the link to get the details (almost all of which are minutiae that don't belong in the article) of toxicity and all the other PubChem stuff. So calls of "censorship" are overblown. Wait until someone deletes the link to PubChem before indicting that person for censorship."

Placing a reference to PubChem in a footnote, (in this case the 90th footnote at the time of this writing) is not equivalent to placing it in the body of the article itself. You are aware of this. Placing a PubChem reference under the "Identifier" column on the right hand side will not be observed by the great majority of readers.

People will more likely notice, read, and be informed by a statement made in the body of the article than if it is in a footnote. Even if a reader notices that it is part of a footnote, that individual may reasonably attribute less weight to it than if it were in the article itself.

On a further note, I must request that the assertion that fluoxetine is acutely toxic appear "above the fold," preferably at the end of the first paragraph. Psychologically, readers typically remember and absorb the first few paragraphs more than the paragraphs which follow, especially in a lengthy article as this one is. Furthermore, many readers do not scroll down, or if they do, gloss over the content. In this article, "Adverse Effects" are discussed way below the fold.

As a separate but related matter, I must also request that the "Adverse Effects" also appear above the fold. Even on TV, when a drug is advertised and described, the pharmaceutical company advertising the drug is required to immediately thereafter identify significant "side effects" of the drug. On Wikipedia, it should be the same. "Adverse Effects" should not appear below the fold in this or in any article pertaining to drugs. 2601:6C5:300:B230:2491:9990:879F:14A5 (talk) 06:26, 12 February 2023 (UTC)