Talk:Nefazodone

Untitled

Nice edits, Rmky87. Thanks. -WanderingHermit.

Argh, I can't figure out how to change the brand name to the chemical name (under the molecInsert non-formatted text here ule picture). Oh well. - Fuzzform 22:12, 14 December 2005 (UTC)

I added a bit about the availability of nefazodone in the US. I will add a detailed section on side effects later, as nefazodone is associated with numerous reports of visual disturbances and anxiety, probably due to one of its primary metabolites, m-chlorphenylpiperazine.
Porkchopmcmoose 22:52, 15 January 2006 (UTC)

Serzone Equals Sleep

I have struggled with depression since my adoloscence and was prescribed Aropax (Sp?) at the age of 18 with no results positive nor negative.

At the age of 23 I tried Serzone after some investigation on the internet. As I recall, the prescription indicated a dose every eight hours. In my case, this resulted in an almost constant state of drowsiness. I would sleep for six or seven hours and awaken in time for the next dose. I quit the stuff after two or three weeks. The causes and effects of depression are wide and varied and, having since beaten the disease after a long struggle, I know that, at least for some of us, the torment may be beaten via a non-pharmaceutical approach. Jones

Nefazodone and Sleep/Libido=

No question that this medication is beneficial with sleep. But it should not be dosed every 8 hours; it can be dosed once daily or twice daily (refer to rxlist.com). Its sedative properties are similar to its "cousin", Trazodone, which is commonly used in the U.S. as a sedative in those that have addiction potential; often used as a sleep medication in Alcohol/Substance abuse treatment centers.

<<< Really? I was always told to take it in the morning (when only taking one per day) because it tends to be "energizing." >>> 71.112.87.162 (talk) 12:01, 20 June 2010 (UTC)

In regards to libido, Nefazodone can be combined with lower doses of SSRIs, since it potentiates the effect of the SSRI (anxiolytic) without having to use full doses of SSRIs which all have noted sexual side effects. Please note, SSRIs, despite being called anti-depressants, are in fact the best anti-anxiety medications on the market. DirkMc (talk) 02:50, 9 July 2009 (UTC)

"Please note, SSRIs, despite being called anti-depressants, are in fact the best anti-anxiety medications on the market." Better than benzodiazepines like Alprazolam and Clonazepam? Better than the Phenelzine? Better than Pregabalin? SSRIs aren't the best anxiolytic medications on the market on any level, including the possible difficulty of withdrawal. About its possible use to decrease the dosage of other antidepressant drugs with worst side effect profile, you're right. --WhereIsMarty (talk) 06:42, 15 September 2009 (UTC)

<<< It depends what you mean by "best." There are a number of reasons they like to prescribe SSRI's for anxiety instead of benzos... they do not tend to produce tolerance, and their effects are very slow, so they have much lower abuse potential than benzos. Benzodiazepene's are most effective for occasional episodes of anxiety, like the ones some people get when flying or speaking in public, whereas SSRI's give baseline coverage for chronic anxiety disorders. I don't know about Phenelzine or Pregabalin. Besides, your little sister is a lot less likely to steal your Nefazodone. :) >>> 71.112.87.162 (talk) 12:01, 20 June 2010 (UTC)

Nefazodone is in fact available in the U.S. Opening paragraph is misleading

Serzone (brand name) is no longer available in the U.S. Possibly not anywhere. Nefazodone (generic name) is available in the U.S. 2602:306:CDB2:4860:2998:8465:43F1:58FB (talk) —Preceding undated comment added 18:26, 27 April 2018 (UTC)

Might be linked to dementia

Serzone might cause liver failure as the article states. It also might contribute to dementia similarly to the anticholinergics which are now strongly linked to dementia.

https://www.health.harvard.edu/mind-and-mood/two-types-of-drugs-you-may-want-to-avoid-for-the-sake-of-your-brain

Footnotes did not reset after edits

I'm not sure why. Can anyone tell me how to fix it? Biolitblue (talk) 08:37, 15 January 2024 (UTC)

Question regarding why Nefazodone edits reverted

You reverted an entry regarding a drug to which I made important edits. You claimed that they content was not WP:MERS. Which content are you referring to?

If you are referring to Pubchem, please be advised that it is MERS compliant. Question about PubChem , Sigma Aldrich and ChemSpider

Are the sources above reliable? Nihaal The Wikipedian (talk) 13:51, 12 August 2020 (UTC)[reply]

PubChem (US NCBI) and ChemSpider (UK RSC) are reliable. Sigma Aldrich is a private corporation (owned by Merck), so it depends on the context. François Robere (talk) 14:32, 12 August 2020 (UTC)[reply]

The other citations were from medical literature.

If you have a bona fide reason to revert, that's ok with me. However, you should then briefly discuss on the talk page what the reasons were for reverting and what specific citations you thought were not MERS compliant. I can then decide whether I want (or can) find citations to bring the article into compliance. Simply reverting and making claims underneath the reversion, without more, doesn't come across as acting in good faith. The goal here is to improve the articles.

As to any NPOV, I can provide cites for those. 2601:6C5:300:3FA0:5871:3CFE:17C8:E90F (talk) 00:01, 16 January 2024 (UTC)

WP:MEDRS, not 'MERS'. Chemical databases may be reliable in some contexts, but the requirements for claims about health are much more stringent. Statements from major medical organizations (like the WHO) or systematic reviews are the standard. Chemical databases, medical research articles, primary studies or sites like 'antidepressantsfacts.com' do not meet the standard. Your personal opinions about corruption at the FDA have no place in this article. MrOllie (talk) 03:30, 16 January 2024 (UTC)

Question about why edits on article were reverted

{{3OR}} Third party requested. See above.

Editor who reverted, whether correct or not, should recuse himself due to his admonishment to me and previous interaction on another topic. Biolitblue (talk) 00:24, 16 January 2024 (UTC)

There were blatant failues of neutrality (highlighting the profound corruption at the FDA) as well as sources that did not actually support the claims in question (chemical database used for health claims), and sources that plainly do not meet WP:MEDRS used for health claims (antidepressantsfacts.com, primary medical studies). Properly sourced text such as the incidence of liver problems was also removed without explanation. I will raise this issue at WikiProject Medicine's talk page for additional comment. There is no policy based reason to for my recusal so I decline that. MrOllie (talk) 03:17, 16 January 2024 (UTC)

1) There were blatant failures of neutrality (highlighting the profound corruption at the FDA):

Nope, you're wrong.

2) Sources that did not actually support the claims in question (chemical database used for health claims), and sources that plainly do not meet WP:MEDRS used for health claims (antidepressantsfacts.com)

Nope, you're wrong. Pubchem is citable to show the lipophilicity of a drug, or any other characteristic of the drug published on that site. I can then use a secondary medical source to show that high lipophilicity of a drug exerts hepatotoxic effects.

If Pubchem has a pictogram, it is also citable for that claim.

Lastly, I didn't cite to antidepressantsfacts.com

3) The information was deleted because it is unreliable, especially given other evidence. The manufacturer's claim, if that was what it was, regarding the incidence of liver problems is out of date and there is more than a credible reason for believing the information is false.

The claim cannot be verified because hepatotoxicity is usually asymptomatic and often takes time to manifest. Liver function tests (which is a misnomer in itself) are not dispositive. ALT for example is a tardive biomarker, and is a biomarker of hepatocellular death, not inflammation or stress.

The bit about stopping the drug if ALT and AST are 3x over the normal limit is not only highly problematic, but could constitute malpractice if you were a physician. Those values represent acute hepatotoxicity and hepatocellular death. I deleted it not only because it is wrong but could subject the site or the author to liability.

4) Your point regarding primary medical sources appears to be correct. I will obtain secondary sources for them, which should not be difficult. And there's the rub: that's what you should have asked me to provide rather than reverting the page again. Something like, "hey, thanks for your edits, but I see you used some primary medical sources. Wikipedia's rules require secondary medical sources. Please amend the page to include secondary medical sources or I'll have to revert it." Biolitblue (talk) 04:27, 16 January 2024 (UTC)

Nope, you're wrong. - The neutrality problem is clear, and your attacks on the FDA had zero basis in reliable sourcing.

Pubchem is citable to show the lipophilicity of a drug, or any other characteristic of the drug published on that site. I can then use a secondary medical source to show that high lipophilicity of a drug exerts hepatotoxic effects. - That is textbook WP:SYN. You cannot combine sourcing in that manner on Wikipedia.

As to your complaint about reverting, I'm not going to argue process with you beyond stating that reverts are part of standard editing practice on Wikipedia. The burden is on you to get consensus for your changes, and it is not normal practice to leave problematic content in an article while someone fixes it. It is removed and is then only restored when it gains consensus. MrOllie (talk) 04:34, 16 January 2024 (UTC)

I find it quite a coincidence that you're interested in this drug and recursion. Biolitblue (talk) 05:05, 16 January 2024 (UTC)

1) I didn't attack the FDA. Where is your evidence? Public Citizen objected to the FDA's decision to keep the drug on the market, but I'm not Public Citizen.

I can countenance your neutrality argument if you think Public Citizen has agenda other than what it purports to be, but I do think it does and I don't think many others would think it does either. I reject the claim that PC is anti-FDA for the heck of it or for politic reasons. The organization is reliable as far as I can discern.

Additionally, the notion that the FDA has some kind of divine right of unassailable authority, and that any editor who cites a group that disagrees with them is being non-neutral, is quite twisted and somewhat authoritarian in posture.

I don't think this idea of neutrality is feasible, proper, or tenable.

2) True.

However, I would imagine that the purpose of the synth rule is to prevent editors from adding things up in a way that produces an illogical or spurious conclusion. This isn't a spurious conclusion via synthing though. In the meantime, I will try to find a secondary medical source.

3) Ok, fair enough. Biolitblue (talk) 05:52, 16 January 2024 (UTC)

{{3OR}} Third party requested.

I'm challenging the following objections raised:

1) The neutrality objection. Please see my response above; and

2) The synth rule objection.

If a simple inference can be drawn directly from existing citable sources, it wouldn't be considered original synthesis and wouldn't violate the SYNTH rule.

In this case, a simple inference that Pubchem's numerical lipophilicity of a drug, together with a secondary medical source showing that high lipophilicity of a drug exerts hepatotoxic effects, is a simple inference.

Thank you. Biolitblue (talk) 06:22, 16 January 2024 (UTC)

I didn't attack the FDA. Where is your evidence? - In this diff you wrote in the edit summary the FDA's corrupt role in approving it and keeping it on the market and highlighting the profound corruption at the FDA in the article. Please don't waste time denying things that are easily found in the page history. - MrOllie (talk) 13:28, 16 January 2024 (UTC)

That was the first draft. The second draft omitted it.

Your tone to me is consistently antagonistic. You are also hounding me. Biolitblue (talk) 22:57, 16 January 2024 (UTC)

Response to third opinion request:

I am responding to a third opinion request for this page. I have made no previous edits on Nefazodone and have no known association with the editors involved in this discussion. The third opinion process is informal and I have no special powers or authority apart from being a fresh pair of eyes.

Concerning 1) The liver toxicity of Nefazodone is mentioned twice in the introduction and several times in the body of the current article. This is sufficient in my opinion. Placing a long section concerning the hepatoxocity with it's own paragraphs on history and pathophysiology, sometimes repeating content already in the article, right at the beginning is undue weight. Parts could definitely be integrated into relevant subsections. Concerning 2) We probably consume a myriad of lipophylic compounds in large amounts every day without going into liver failure. The claim that lipophilicity is a relevant factor in Nefazodone's hepatotoxicity needs to be backed up by a source establishing this connection. As written, it's definitely WP:SYN. A subsection on the pathophysiology of Nefazodone in the liver would be a good addition, but it needs WP:MEDRS sources. MaligneRange (talk) 09:26, 16 January 2024 (UTC)

Thank you for promptly reviewing the matter and responding to my request.

1) The hepatotoxicity section in the beginning is not given undue placement because it is one of the most problematic drugs still on the market. It has been permanently withdrawn in many countries. The continued availability of the drug in the United States has been criticized in the literature, as has the FDA's decision and the manufacturer's conduct regarding the marketing of the drug. I left that out due to objections by another editor, to avoid politicizing, and to avoid overcomplicating the article regarding matters that do not pertain to the drug itself, which should be the focus.

The undue weight rule states that "[a]n article should not give undue weight to any aspects of the subject, but should strive to treat each aspect with a weight appropriate to its significance to the subject. (emphasis in bold added).

I can place it lower down in the article by putting more background information at the beginning, but I must request that it appear prominently above the fold.

The "second" reference to hepatotoxicity being mentioned is discussed in the Background section. I did not prepare that version of the article, but I can and agree it should be deleted.

2) Your assertion that consuming myriad other lipophilic compounds without experiencing hepatic failure, implying that fat presumably from food sources and the lipophilicity of a drug are comparable with respect to hepatotoxicity, demonstrates a lack of understanding of the subject matter. It is false equivalence.

You are also implying that acute liver failure after a short duration of ingestion of this drug is the only problem. It is not. Acute liver failure, DILI induced fibrosis, and extracellular matrix formation on the liver parenchyma are major concerns if this drug is consumed for several months at the doses prescribed for depression. Sometimes antidepressants are prescribed and consumed for years or indefinitely, which is a profound concern. The consumption of other medications often accelerate disease progression and injury type. Those with depression who are prescribed an antidepresssant are often prescribed other drugs as well.

I'll accept your ruling that it is WP:SYNTH but you did not explain your reasoning. It is merely conclusory, even if it is correct. I don't understand why it is definitely WP:SYNTH given the reasons I stated.

"A subsection on the pathophysiology of Nefazodone in the liver would be a good addition." I'm not sure we know the mechanisms for sure. Although some secondary medical references exist that identify in vitro tests which found that mitochondrial perturbations and endoplasmic reticulum stress are implicated, these tests do not necessarily recapitulate similar effects in vivo in humans. Biolitblue (talk) 23:43, 16 January 2024 (UTC)

Your edits continue to contain the same sourcing (failure to comply with WP:MEDRS requirements) and WP:SYN issues, POV pushing, and unjustified deletions. MrOllie (talk) 04:29, 17 January 2024 (UTC)

Your objections should have some explanation.

As to WP:MERS, I cited a secondary source and cited the primary source. I'm looking at other medical articles and many go with primary sources only. What specifically is not compliant with WP:MERS?

Where is there POV pushing? I removed the reference to Public Citizen. The other references to PC were in the previous draft. What content is ok with you and what isn't? Maybe I can delete what you think is objectionable so we can move on without edit warring.

I didn't delete stuff, I moved it around. In fact, I deleted a reference in the existing version to hepatotoxicity to remove a redundancy, which MaligneRange requested. Biolitblue (talk) 19:18, 17 January 2024 (UTC)

Re: WP:MEDRS, a secondary source is not the standard MEDRS requires. You've been told all this stuff before, for example at Talk:Fluoxetine#Chemical_vs_Medical_Toxicity_of_Fluoxetine. I'm not going to go cite by cite with you. You can either start by proposing smaller edits on the talk page, or you can go read and understand the guideline.

Re: POV pushing, The insertion of your personal opinions, for example 'unfortunately' and your overall tilting of the article away from the mainstream view and towards the view that it is toxic poison, which is also being commented on by the 3O's you have been requesting.

Re: I didn't delete stuff You plainly did delete the incidence figures again. It is really difficult to assume good faith when you keep claiming things never happened (as you also did above with the FDA stuff, and your claim that you didn't cite antidepressantsfacts.com) when it is plain to see that you did in fact do these things in the article history. - MrOllie (talk) 19:29, 17 January 2024 (UTC)

You're wrong. You continue with this. Why?

Again, what edits are you ok with? Editors are supposed to cooperate and iron out differences. Biolitblue (talk) 20:16, 17 January 2024 (UTC)

You're wrong. - It's all right there in the article history for anyone to check.

You continue with this. Why? Your edits are not policy compliant and make the article worse.

what edits are you ok with? Edits that proceed with WP:CONSENSUS support from the article talk page. (Requesting third opinions and then telling them they're wrong when they disagree with you is not consensus) and that comply with important Wikipedia policies, such as WP:MEDRS, WP:NOR, and WP:NPOV. - MrOllie (talk) 20:44, 17 January 2024 (UTC)

No, you're time wasting, You claimed that I'm constantly deleting the same content over and over again.

Nope, where I thought they were incorrect on some points I said so. Overall, I asked what everyone thinks is ok so we can try to work out differences.

Your comment of proceeding with WP:CONSENSUS is circular and condescending. I know this and am trying to comply but I'm not getting cooperation regarding what we can all accept. Biolitblue (talk) 20:53, 17 January 2024 (UTC)

No, you're time wasting, You claimed that I'm constantly deleting the same content over and over again. You clearly are. But if you think I'm the one who is being dishonest here, feel free to report that to WP:ANI. MrOllie (talk) 20:59, 17 January 2024 (UTC)

1) It's still undue weight as per the reasons I gave above. This isn't a website for US-specific PSAs, but an encyclopedia. Concerning your request to place it prominently above the fold: I have to correct my statement above where I said it was mentioned twice in the introduction, all of the three paragraphs of the introduction mention it's hepatoxicity. It doesn't get much more above the fold than that.

2) Labeling something as a drug tells us nothing about it's biochemistry. Whether we classify something as a drug or a food is completely irrelevant to how the liver metabolizes it.

3) "Acute liver failure, DILI induced fibrosis, and extracellular matrix formation on the liver parenchyma are major concerns if this drug is consumed for several months at the doses prescribed for depression." This might be true, but would also need MEDRS sources.

4) "I'm not sure we know the mechanisms for sure." That seems to be the case, which should be shown in the article instead of original research. In vitro mechanisms can imho be added to the article if they are clearly labeled as such.

Concerning your latest edit: I'm not sure why you've decided to remove so much content, and I think MrOllie's reversion was justified for the reasons they gave. Again, there's definitely parts in there that could be integrated into the article. MaligneRange (talk) 08:26, 17 January 2024 (UTC)

1) "This isn't a website for US-specific PSAs, but an encyclopedia."

I know, and that's a gratuitous statement.

I think mentioning the cases of liver failure and the FDA evaluation of the drug underneath where I placed it is reasonable. Given that the problem is serious, it doesn't violate the undue weight rule since the rule clearly states that weight may be given in accordance with its significance. It is mentioned in different contexts: in a context involving reported cases and in an FDA evaluation. Simply stating that it is mentioned more than once doesn't mean the issue is being flogged.

Where do you think the information belongs?

2) the word, "it's" should be "its" for your information.

"Whether we classify something as a drug or a food is completely irrelevant to how the liver metabolizes it."

No, you're wrong.

3) Ok.

4) I know I can, but since you are raising so many objections I'm trying to stick with the least controversial stuff. Biolitblue (talk) 19:35, 17 January 2024 (UTC)

You've been told more or less the same thing by three people, two of which responded to the 3OR you yourself placed. Your arguments have been heard, everyone but you agrees they don't hold and you've been given the reasons why. Seeing your replies here, especially the later ones, I'll have to agree with Ollie's and Anon's assessment: Seek consensus first and/or take a break. MaligneRange (talk) 08:01, 18 January 2024 (UTC)

FYI Biolitblue has been blocked and most likely will not be responding here any further. MrOllie (talk) 13:14, 18 January 2024 (UTC)

Response to third opinion request:

I agree that Biolitblue's version (i.e. Jan 15) went too far. Unless a reliable secondary source states something to the effect of "nefazodone's continued availability in the United States is evidence of the FDA's corruption", don't put that in the article. I understand and sympathize with Biolitblue's desire to minimize harm, but a crusading zeal for justice doesn't excuse bad sourcing. If it's so definitely true and important, such a statement should be published somewhere out there. At very least, Wikipedia's neutrality policy advises against such editorializing language. Additionally, such statements likely to be challenged as "All of these factors make the drug poisonous to human health in the doses in which it is administered," should definitely be cited. Furthermore, I don't see why, as in this edit, we must remove the fact that it's an atypical antidepressant, the incidence of liver damage, or the medical uses. I think that the previous explanation of nefazodone's liver toxicity and (un)availability was sufficient. Maybe we can add the fact that it's ranked in DILIrank severity class 8 (ideally with more lay-accessible wording), but I'm not sure I see the benefit of the larger changes, which seem still motivated by the (very non-neutral) feeling that the preexisting article was insufficiently opposed to the drug's availability—the preexisting article seemed to be plenty plain in stating that it is banned in some countries and has serious liver toxicity, which seems sufficiently alarming to me, with the issues covered well enough. Finally, I don't have much comment on the MEDRS qualifications of the three paragraphs under "Contraindications" beginning with "Furthermore, hepatotoxicity is likely caused", "The metabolism of nefazodone", and "Liver biopsy following nefazodone"—I invite more experienced medical editors to look at the usability of those sources and whether those three paragraphs belong in the article (e.g. under WP:DUE)—but the final paragraph seems to edge into synthesis in implying that nefazodone (via hepatotoxicity) harms the brain. My advice to Biolitblue, who seems to have a valuable body of medical knowledge, is perhaps to take some time away, work on less contentious topics (than this or, for example, Israel–Palestine), let the emotions fade, and maybe come back when better acquainted with the relevant policies. — Anon423 (talk) 05:11, 17 January 2024 (UTC)

1) "I agree that Biolitblue's version, i.e. "Jan 15th" and the rest of the first paragraph._

Stop. This is blatant time wasting. I dropped that version, which is clearly evident in the article history record.

2) Dropping the the incidence of liver damage is needed because of the reasons stated earlier. Other stuff is fine.

3) "Maybe we can add the fact that it's ranked in DILIrank severity class 8 (ideally with more lay-accessible wording)."

Most people probably do not know what DILI stands for.

4) "The preexisting article seemed to be plenty plain in stating that it is banned in some countries and has serious liver toxicity, which seems sufficiently alarming to me, with the issues covered well enough."

No, it is not but I'm willing to compromise.

5) Your third paragraph, no problem.

6) "My advice to Biolitblue, who seems to have a valuable body of medical knowledge, is perhaps to take some time away, work on less contentious topics (than this or, for example, Israel–Palestine)."

Blatant condescending and sarcastic comments violate Wikimedia's code of conduct. Biolitblue (talk) 20:01, 17 January 2024 (UTC)