Talk:Selective serotonin reuptake inhibitor

Permanent neuropsychological changes

From the article

Permanent neuropsychological changes Since the early 80's scientists have used a technique called neonatal clomipramine to produce animals used in depression research. If rats are given the tricyclic antidepressant clomipramine when they are 8–21 days old they will develop behavioural changes in adulthood which resembles depression in humans.[50][51] In 1997 Lundbeck found that treatment with the SSRI LU-10-134-C, which only differs from their product citalopram by two atoms could give similar results as clomipramine.[52] Later it was found that neonatal citalopram and escitalopram makes persistent changes in the serotonergic transmission of the brain resulting in behavioral changes, [53][54] which are reversed by treatment with antidepressants.[55] By treating normal and knockout mice lacking the serotonin transporter with fluoxetine scientists showed that normal emotional reactions in adulthood, like a short latency to escape foot shocks and inclination to explore new environments were dependent on active serotonin transporters during the neonatal period.[56][57]

But when young mice were treated with the SNRI desimipramine they developed to normal adults, which suggests that serotonin and noradrenaline has different effects in the developing brain. For humans, the developmental stage sensitive to SSRI:s corresponds with the last trimester to the first years of life. A study showed that 4-year old children perinatally exposed to SSRI:s behave normally, however the young mice and rats also seems to be normal until they reach puberty and develop their behavioural disturbances.[58][59]

The mechanism is currently unknown, but it seems that early life overstimulation of the 5HT-1 receptor which acts like a thermostat for the serotonin production results in low serotonin production after puberty.[60]

Interesting, but mostly irrelevant. Why? Mice brains are different to human brains. Drugs affect mice different to human. Mice puberty is different to human puberty. Knockout mice are different to mice. I'm not entirely convinced that the fact that knockout mice, when given a rediculously high dose of a SSRI (for their weight), develop problems after puberty, is all the relevant to humans. This isn't even refering to neonatal SSRIs. This section is very long, confusing, and uncertain relevence.

Incidentally, SSRI use hasn't been shown to be associated with any real behavioural differences in those aged 4-5 and a little earlier. This link failed to be proven in quite a few studies. Naturally though the above deals with post puberty, but I thought this was a little interesting. Depression and anxiety is however associated with behavioural alternations. I had a lovely selection of articles I roughly summarised, but I forgot to save them.

I suggest axing the above quoted section, or listing the fact that SSRI use hasn't been associated with behavioural differences and *maybe* consider having 1 line on mice. 203.5.70.1 (talk) 16:58, 15 October 2009 (UTC)

You suggest that because mice brains are different to human brains, it reduces the impact of the study (which I don't necessarily disagree with), yet many of the studies of SSRIs which show their alleged benefits are done via precisely the same route. You can't have it both ways. GimpyFauxHippy (talk) 13:04, 24 January 2010 (UTC)

There is no discussion of the use of SSRI's in anxiety and panic disorder. Christinedoby (talk) 03:22, 2 April 2013 (UTC)

Pregnancy and SSRIs

Really needs referencing, and I don't really know or have enough time to figure out how to reference the articles, but I can point out the articles in question if need be.

Combined my previous edit with another editor's work, I hope it's acceptable? Evidence regarding SSRI's teratogenesis effects is a little "all over the place" due to the methodological difficulties and conflicting evidence (quite a few studies which have found nil increase). SSRIs have been found to be weakly associated in one study or another to be linked with pretty much every deformity under the sun, and yet found by most other studies to not be associated at all. Worth a slight mention in general though, but paroxitine and the septal effects has been replicated in enough studies to probably deserve special mention. Sertraline and other SSRIs in general (with the exception of paroxitine) haven't been associated with septal defects in any other studies in my knowledge.

The fact it's common to continue SSRIs in pregnancy and why I thought is also quite important, and I would like to leave it there.203.5.70.1 (talk) 16:22, 15 October 2009 (UTC)

September 2007 indicates FEWER suicides in subjects taking SSRI, not more.

In quotation from the article: "Brown found that suicide attempts were dramatically lowered once antidepressant medication began, indicating an overall benefit of these newer medications. Also, very few people who died from suicide had been taking antidepressants.

He also found consistent reductions in suicide across counties as well as across countries during the time when there was increased use of antidepressants. Now that the overall level of antidepressants have decreased since the FDA warnings, there is very early evidence of an upturn in youth suicides.

"With the FDA warnings there has been a rapid lowering of antidepressant prescriptions, and there has been a corresponding increase in youth suicides" noted Brown. "We found similar results in the Netherlands once the warning was broadcast there as well."

How did the misconception that this study shows a higher tendency sneak into the article? I'm changing that. Hugi (talk) 00:52, 29 May 2008 (UTC)

I've just been through the SSRI and aggresssion section and sub-sections like a blowtorch through an ice cube. I am certain there are reliable sources that discuss the relationship, Breggin is one of them, but the referencing was terrible and some references outright contradicted the statements contained in the article. I'm sure a portion of this is a limitation of full-text versus abstract, but if the abstract says X reduced suicide, it's mis-representation to quote mine the article for only the cirtical statements without demonstrating the main conclusion. Blech. I would dearly love to see the links between SSRIs and suicide to appear in the article, but not based on blogs and fake sources. WLU (talk) 19:01, 29 May 2008 (UTC)

Just had a look over, and I think this section needs to be redone. I think it should make more of a mention of the impact of age on the risk change (ie adolescents higher risk of suicide, anyone else lower risk), and distinguish between attempted suicide and completed suicide (very important of course). There's a lovely FDA metareview article in 2006 on the subject. I think it's also worth stressing in the article that suicide is relatively rare, and the absolute increase in risk (if any) is very low. Also, untreated depression (obviously) is a huge risk factor for suicide anyway, much more than the use of SSRIs. But in general, wikipedia is pretty lousy for this sort of stuff. POV warriors tend to cherry pick the odd study (or even a statement from a study) that stands out from the crowd and then try to make things sound as alarmist as possible /soapbox 128.250.5.247 (talk) 05:15, 12 October 2009 (UTC)

Suicidality in children

Based on the references and the discussion above, I changed "causes suicidality" to "may increase the risk of suicidality", since there seems to be significant controversy on this issue in the literature. This was reverted with a suggestion to discuss the change here. I'd say that "causes" is too strong, especially given the results of the Brown study discussed above. Klausness (talk) 13:42, 6 June 2008 (UTC)

First of all, both the FDA and MHRA (the UK regulatory agencies) hold that antidepressants in general, including SSRIs, cause suicidality in children (emphasis mine). These conclusions were made after the careful, case-by-case analysis of the occurrences of suicidality in double blind trials on children. I am not kidding, the FDA actually hired a group of suicidology experts from Columbia University who went, one-by-one, through the raw descriptions of all the suspicious cases of suicidality in childrens trials FDA requested fron the companies. The statistically significant increase of suicidality in double-blind trials in the antidepressant groups as compared to placebo was demonstrated beyond any doubt. If a double-blind trial demonstrates some effect it is generally hold to be causal. (Otherwise you would have to agree with such ridiculous statements as: Antibiotics are associated with improvement of acute bacterial infections, but they may not be the cause of this improvement). Thus there are warnings in the US regarding the use of antidepressants in children, and outright counterindication of such use in the UK.

On the other hand, the Brown study included adult patients, for whom the consensus is that antidepressants does not cause suicidality. In addition, the Brown study is not controlled but epidemiological, so it is inherently weaker. Paul Gene (talk) 14:42, 6 June 2008 (UTC)

I understand that these conclusions were reached after careful analysis, but many experts apparently disagree. Also, the standard way to talk about untoward side effects that occur for some, but not most, people is to say something like "may cause". To the lay person (and wikipedia is written for the lay person), "causes suicidality" means "if you take this, you will become suicidal", and that's clearly not true. My wording of "may increase the risk of suicidality" means "if you take this, you may become suicidal (or more suicidal)", which is exactly what the FDA and MHRA concluded. We could also say "increases the risk of suicidality" -- that way it sounds more definitive while still making it clear that we're talking about an increased likelihood, not a certainty. Klausness (talk) 15:18, 6 June 2008 (UTC)

I am going to change it to "can cause" like with sexual side effects: "SSRIs can cause various types of sexual dysfunction such as...". There is about the same level of certainty. Paul Gene (talk) 16:33, 6 June 2008 (UTC)

Hmm. January 29, 2009 sees the Army reporting the highest suicide rate in history, while Paxil is one of two meds approved by FDA for PTSD. Maybe there's a connection? Ya think? Also the suicidality being acknowledged in children and young adults up to age 18 is as much of a joke as the Black Box Warnings. There is no biological mechanism that keeps maleffects of SSRIs from occurring in adults - And "FDA's strongest warning was never even used on drugs before they applied it to SSRIs - it was only used on cigarrette packaging - which is where those in FDA likely got the idea while they were smoking like expectant fathers, trying to come up with yet another way to obviate appropriate drug safety regulation - AND TAKE THE HARMFUL PRODUCTS OFF THE MARKET. Guess New Boston Tea Party strikes again. Wise up. Thanks.

Where have you found the data showing the SSRIs may "cause" suicidality? Most studies have only found a link between the two, so the data generally doesn't indicate a causal relationship. The FDAs publication in 2003 (which majorly covered depression trials, naturally increasing suicidality risk) found problems with SSRIs. But since then, lots of research (Gibbons, Bridge, Olfson, etc.) suggesting that there is an negative relationship between SSRIs and suicidality. While there have been studies finding no significant benefit (especially for MDD), there is no associated risk of suicidality. Also, you should change it to "certain" SSRIs. Prozac has been cleared multiple times and virtually all costs-benefits analysis have found that it reduces sucidiality. —Preceding unsigned comment added by 128.42.164.188 (talk) 06:30, 5 February 2010 (UTC)

Programmed cell death by SSRI

On August 2 I added a very small note on possible neurotoxic effects of SSRI. It is about apoptosis. (Evident in vitro.) My entry as well as the references were deleted. It's a pity, I think the readers have the right to be informed....

http://www.ingentaconnect.com/content/hum/jmn/2005/00000027/00000001/art00004

Ok, I see it is now under Neuroprotection! Well, but it also shows neurotoxicity... —Preceding unsigned comment added by 62.47.180.13 (talk) 22:11, 6 August 2008 (UTC)

Can somebody put this in terms a welder (who's having antidepressants pushed upon him) can understand? —Preceding unsigned comment added by 68.17.100.179 (talk) 22:17, 14 September 2008 (UTC)

Removed Weasel Word Warning from "Criticism" section

Almost all claims in this section are well-referenced and are not empty statements in the sense of "People say they don't always work...", "Some believe that it does more harm than good...", etc. The only sentences in the section that are written in this way are: "Biopsychiatrists believe that, among other factors, the balance of neurotransmitters in the brain is a biological regulator of mental health. In this theory, emotions within a "normal" spectrum reflect a proper balance of neurochemicals, but abnormally extreme emotions, such as clinical depression, reflect an imbalance. Psychiatrists claim that medications regulate neurotransmitters, and many if not most psychiatrists also claim they treat abnormal personalities by removing a neurochemical excess or replenishing a deficit." But that's simply summing up the general point of view of modern psychiatry: restoring chemical imbalances in the brain. If there are a lot of experts that think that this is not at all what modern psychiatry is about, then maybe these sentences should be removed altogether. The sentences don't form the core of the 'criticism' section. The core is that there are a number of studies that take into account *all* available data on the efficacy of the drugs, and that the conclusions from these analyses are that the drugs are not as useful as is generally portrayed. —Preceding unsigned comment added by 82.74.127.167 (talk) 17:30, 16 December 2008 (UTC)

List of SSRIs that don't cause Tinnitus

I've heard that Tinnitus is a common side effect with SSRIs. I've been trying to find out which ones don't cause Tinnitus, I think it may be helpful to add a section listing, which SSRIs are better for people who have had Tinnitus as a side effect before, or Tinnitus in general.Violet yoshi (talk) 12:48, 23 June 2009 (UTC)

Potential source

[1] may be a valuable source for the pharmacodynamics section, if it mentions 5-HT2A downregulation. I can't get to my university library to view the full article for several days. Jennifer500 (talk) 03:02, 1 January 2010 (UTC)

That particular source only includes one sentence about 5HT2. Looking at [2], it seems that much of the pharmacology section's unsourced paragraph about 5HT2 neurotransmission is incorrect. Yes, the stimulation of 5HT2a and 5HT1a receptors which occurs during SSRI administration downregulates 5HT2a. But this is a good thing: it occurs when the antidepressant effects of SSRIs become apparent. Also, deceased suicidal and otherwise depressed patients seem to have had more 5HT2a receptors than normal patients, suggesting that 5HT2a overactivity is involved in the pathogenesis of depression. I am modifying the paragraph to include the source, and for conformity to it. Jennifer500 (talk) 23:19, 2 January 2010 (UTC)

Comparison with benzodiazepines irrelevant

Some Wikipedia authors seem not to be able to resist the temptation to insert warnings about benzo withdrawal independent of the the topic being discussed. I've lightly edited the section in this article that compares benzo and antidepressant potential withdrawal concerns. I resisted the temptation to point out that Effexor withdrawal, if one refers to withdrawal sites, appears to be more difficult that benzo withdrawal for many people and that even Heather Ashton (her opinions are well-meaning, but hopeless dated) states that about 50% of benzo users do not exhibit benzo withdrawal symptoms-making any blanket statement about benzo withdrawal invalid. Dehughes (talk) 22:45, 7 April 2010 (UTC) David Hughes

Brain-derived neurotrophic factor's role in SSRI and depression

The following comes from a paper I in progress of writing regarding PTSD and the use of SSRIs. It's directly applicable to this article as it describes one of the mechanisms of SSRIs.

This is done by SSRIs acting on signal pathways such as cAMP (Cyclic AMP) on the postsynaptic cell, which leads to the release of Brain Derived Neurotrophic Factor (BDNF). BDNF enhances the growth and survival of cortical neurons and synapses. Thus, the use of SSRIs may actually help to reverse the hypoconnectivity previously described. (Kolb and Wishhaw, 2006) Source: Kolb, Bryan and Wishaw Ian. An Introduction to Brain and Behavior. New York: Worth Publishers 2006, Print.

I am hoping we'll be able to add in the BDNF info to this article as I think it's missing a major facet without it. Basket of Puppies 07:00, 20 July 2010 (UTC)

Efficacy

This paper looks relevant to the discussion in the efficacy section but I can't access the full text: "In 'Initial severity and antidepressant benefits', Kirsch et al. conducted a meta-analysis of data from 35 placebo controlled trials of four newer antidepressants. They concluded that while these drugs are statistically significantly superior to placebo in acute depression, the benefits are unlikely to be clinically significant...we argue that Kirsch et al.'s is a flawed analysis which relies upon unusual statistical techniques biased against antidepressants. We present results showing that re-analysing the same data using more appropriate methods leads to substantially different conclusions."--86.23.82.164 (talk) 16:24, 1 August 2010 (UTC)

I agree the section seems too one-sided. There has been criticism on the used statistical methods, and most importantly on the use of FDA licensing trials for quantifying the benefits. Given that the FDA requires two positive trials and disregards failed ones for a drug to come on the market, a company will choose the fastest and cheapest way to meet these minimum requirements, ie short duration, no proper screening of candidates and most importantly only designed to show a statistically significant result as required by the FDA. They have no reason to optimize duration and dosage for best clinical results in these trials, yet the meta-study uses the results as such. So basically, to judge the potential efficacy of these drugs, Kirsch et al. took only data from small scale trials, some more than 20 years old, that were set up to show a mere statistical significance, and ignoring any studies that might have been more suitable for their purpose. And they mention publication bias in their meta-study... The other study that is referenced used only six FDA licensing trials with a total of 718 patients. Some replies to Kirsch's article: http://www.bmj.com/content/331/7509/155/reply 94.227.1.33 (talk) 07:24, 14 August 2011 (UTC)

In his book  Bad Science,  Goldacre makes the case that SSRI's  are not effective.

http://en.wikipedia.org/wiki/Bad_Science_(book)#Chapter_10:_Is_Mainstream_Medicine_Evil.3F — Preceding unsigned comment added by 209.78.20.61 (talk) 22:42, 14 August 2012 (UTC)

This section has been removed ("Efficacy") but there are still links to it within the document. Anyone want to propose either putting it back in or changing the links?

Jason A. Jensen of USA (talk) 03:47, 29 May 2013 (UTC)

Sexual side effects

"Initial studies found that such side effects occur in more than 80% of patients, but since these studies relied on unprompted reporting, the frequency was probably overestimated. In more recent studies, doctors have specifically asked about sexual difficulties, and found that they are present in between 17%[38] and 41%[39] of patients." This is incredibly unlikely (people have a known unwillingness to raise sexual issues unprompted) and I have seen books saying the exact opposite. If memory serves, under Eli Lilly's original trial it was reported infrequently, but when someone did a follow up and specifically asked if people suffered sexual side-effects, the percentage of positive responses was huge; I do have the figure of 80% in my head, though I don't know why.

Because this says the exact opposite of what it logically ought to, I suspect this is a malicious edit made at some point and not picked up. If someone could check sources and edit appropriately, that would rule. --Matthew Proctor (talk) 12:17, 11 August 2010 (UTC)

OPED in lede?

The passage The term SSRI is somewhat of a misnomer, invented by the pharmaceutical companies who developed these drugs. Rationally, they should be referred to as SRIs, as dopamine reuptake inhibitors and norepinephrine reuptake inhibitors are referred to as DRIs and NRIs respectively, regardless of their selectivity. seems to be somewhat WP:OPED and perhaps WP:POV. Would it be better to note simply that the phrase doesn't match an existing naming pattern and move it out of the lede? Preferably with references?Autarch (talk) 21:41, 16 October 2010 (UTC)

I wouldn't call it editorialising, it is true that it was invented by the pharmaceutical companies who invented those drugs... they called them "selective" because they thought it would distinguish them from the other antidepressants available at the time, and thereby to give them more zeal. --Axxaer (talk) 05:06, 13 December 2010 (UTC)

It's an obvious example of editorializing, original research, and POV. As with the stuff above about "an untested hypothesis." I'm going to fix that presently. 205.211.141.188 (talk) 19:35, 1 June 2011 (UTC)

Improve the sentence: "Rationally, they should be referred to as SRIs, as dopamine ..."

The sentence in the article "Rationally, they should be referred to as SRIs, as dopamine reuptake inhibitors and norepinephrine reuptake inhibitors are referred to as DRIs and NRIs respectively, regardless of their selectivity." could be phrased more clearly.

Is what is meant: "Rationally, they should be referred to as SRIs in order to be consistent with using the term DRIs for dopamine uptake inhibitors and the term NRIs for norepinephrine uptake inhibitors." ?

Tashirosgt (talk) 22:36, 17 December 2010 (UTC)

"Selective" serotonin reuptake inhibitor is misleading as it suggests that this medication selects a specific kind(s) of serotonin. However, as long as the explanation of the name is present, there is no harm. Perhaps the explanation could be a little clearer. We can't unilaterally change the name that drug companies use. No one but us would know what an SRI is.Christinedoby (talk) 03:35, 2 April 2013 (UTC)

Possibly unnecessary weasel words re. "Post-SSRI sexual dysfunction"

This section starts with the words: "According to one source." Which sounds like weasel words to me; and IMHO, doesn't belong on Wikipedia. I'm not criticising the argument, I just think the caveat is unnecessary. Also, I've no doubt there are several reliable citations that could support the original claim. —Preceding unsigned comment added by 86.16.20.52 (talk) 00:40, 18 December 2010 (UTC)

Also, this section is woefully lacking in references. I don't doubt that some of this is true, but how do I know which issues have good evidence behind them and which have little or none? —Preceding unsigned comment added by 86.16.20.52 (talk) 00:46, 18 December 2010 (UTC)

Re: SSRIs versus TCAs

I think the conclusion of this section (equality of efficacy between SSRIs and TCAs in depression) is, if not incorrect, then at least too global, and somewhat misleading. TCAs are a far too diverse group of agents in order to compare them with SSRIs who, as the name says, affect more or less serotonin only (yes, there are pharmacological differences between them, but they are minor). Amitriptyline or clomipramine are not the same as desipramine, for example. It would be hard to find a clinician who says that, say, citalopram has the same efficacy as clomipramine, particularly in severe depression. Even the one source that is referenced says in the abstract already that amitriptyline is more effective in in-patients (who are likely to present more severe forms of depression). I will try to find some more references, comparative trials and so on, but I was gonna see whether people would agree with me or not. C.d.rose (talk) 12:12, 13 January 2011 (UTC)

SSRIs versus 5-HT-Prodrugs

The section titled like this is not at all talking about Serotonin Prodrugs but only explaining why Serotonin itself cannot be directly administered. Could a knowledgeable person update this?

If Dopamine Prodrugs + Decarboxylase inhibitor (to assure that the prodrugs are metabolized in the brain) work fine for Parkison (which is caused by a lack of Dopamine) then why shouldn't Serotonin Prodrugs + Decarboxylase inhibitor work fine for Depression, which is caused by a lack of Serotonin? —Preceding unsigned comment added by 141.53.210.36 (talk) 19:03, 12 May 2011 (UTC)

Yes, this text of this section does not relate to the title at all. richard.rankin@ieee.org — Preceding unsigned comment added by 66.188.106.93 (talk) 13:16, 5 August 2011 (UTC)

IQ and drinking water

A 16-year old reported a 30 point drop in his IQ after using the SSRI prozac.(see: "SSRI Babies") Prozac is commonly found in the drinking water of the United Kingdom and Canada.(see: "Prozac in Drinking Water? Likely So", "Drinking water contains traces of nine drugs, new study finds", "Stay calm everyone, there's Prozac in the drinking water")

Petey Parrot (talk) 03:40, 14 June 2011 (UTC)

The above are not reliable sources. Sorry, but it cannot be included in the article unless the sources are reliable. Basket of Puppies 10:28, 14 June 2011 (UTC)

Lawsuits

Changed the text from

The inclusion of the black box warning may have led to a decrease in prescriptions of SSRIs and a decrease in suicide. to: "..and an increase in suicide."
Because that is what the first referenced article claims (can't access the second reference) The article reads:
"Some medical professionals, including the National Mental Health Association, blame the effect of the "black box" warning that the U.S. Food and Drug Administration put on antidepressants in 2004, the year before suicide rates rose precipitously. " 94.227.1.33 (talk) 13:50, 15 August 2011 (UTC)

pov

A widely criticised study that was carried out by a guy known as a big fan of placebo effect and of the use of hypnosis in medical procedures. The studies used were carried out to meet the FDA standards for marketing of the drugs involved and they satisfied those criteria. Misusing those trials to prove things they were not designed to test is intellectually dishonest.

And to quote from Meta-analysis: If a meta-analysis is conducted by an individual or organization with a bias or predetermined desired outcome, it should be treated as highly suspect or having a high likelihood of being "junk science". From an integrity perspective, researchers with a bias should avoid meta-analysis and use a less abuse-prone (or independent) form of research. 84.197.184.6 (talk) 04:01, 9 November 2011 (UTC)

Hi, not sure how to reply, but this is a different person. I would also like to point out that this one study being prominently featured in the first paragraph is a bit ridiculous. Why does it have more merit than any other study done? Why prominently display it? EDIT: this entire article is rife with politicization. 198.53.43.19 (talk) 03:56, 15 February 2012 (UTC)

Even though I added some of it, I agree that it is being given undue weight in the lede. There should be a sentence mentioning the dispute, referring to that study and others. The details of the study should be in the section below. I'll probably make the edits in a few days if no one else does. - Maximusveritas (talk) 01:57, 16 February 2013 (UTC)

Suicidiality Original Research

The statement ending the "Suicide Warnings" section stating that concerns about increasing suicides among children were allayed by the cited CDC annual mortality survey is an original synthesis, as SSRIs are not referred to in the CDC report. Thus is is disallowed by the "no original research" policy (http://en.wikipedia.org/wiki/Wikipedia:OR ). Strictly speaking, it is not a definitive conclusion, as it is possible that increased suicides due to declining SSRI use could have been offset by other factors so that no net increase was apparent. — Preceding unsigned comment added by Alfred Bertheim (talk • contribs) 21:05, 2 March 2013 (UTC)

Neurological changes due to SSRI use in infancy

While MEDRS standards do not completely forbid the use of primary reference s or of animal studies, they do discourage both. As there is not a single citation in this section that is not both animal research and primary research, I think it may be considered to be both poorly referenced and given undue weight. I'd like to suggest either reducing it considerably or eliminating it altogether. These compounds have been around for 2 decades and have been taken by tens of millions of people. If the concerns raised in this section were representative of mainstream thought among experts, it should be possible to identify multiple secondary references of studies in humans by now. Alfred Bertheim (talk) 23:14, 2 March 2013 (UTC)

2010 review

A 2010 review reached similar conclusions: in mild and moderate depression, specifically that the effect of SSRI is very small or none compared to placebo, while it is clinically significant in very severe depression. However, this analysis included only 6 studies out of the over 2,000 that have been done, involved just 2 medications, and did not involve studies with placebo washout periods typically used as controls.

These investigators were only able to get patient level data from 6 trials as the others they asked refused to give them the data they needed for the meta-analysis. This is an equally important point IMO.Doc James (talk · contribs · email) (if I write on your page reply on mine) 12:40, 27 March 2013 (UTC)

A vote to remove a paragraph under the "Pharmacodynamics" heading

The paragraph: "However, there is one counteracting effect: high serotonin levels will not only activate the postsynaptic receptors, but also flood presynaptic autoreceptors, which serve as a feedback sensor for the cell. Activation of the autoreceptors (by agonists like serotonin) triggers a throttling back of serotonin production. The resulting serotonin deficiency persists for some time, as the transporter inhibition occurs downstream to the cause of the deficiency and therefore, is not able to counterbalance the serotonin deficiency. The body adapts gradually to this situation by lowering (downregulating) the sensitivity of the autoreceptors.[99]" sources a publication that states there was no effect on presynaptic autorecptors. From the abstract: "Chronic treatments had no effect on presynaptic 5-HT1B autoreceptors, functionally evaluated by measuring 5-HT1B-mediated inhibition of depolarization-induced [3H]5-HT release from cortical and hippocampal synaptosomes." although this paragraph may be true, this study does not show it — Preceding unsigned comment added by 173.206.144.178 (talk • contribs) 00:06, 6 July 2013‎

Hi User:173.206.144.178! I cannot judge if you are correct or not, but I put a dubious-tag at the end of the paragraph, and I hope someone comes along who knows more and decides if the paragraph should be kept or if the tag should be removed. Lova Falk talk 14:54, 3 January 2014 (UTC)

This is a bit confusing but I don't think there is actually any contradiction. When the paper says that there was no effect on autoreceptors, I take it to mean that there was no increase or decrease in the number of autoreceptors or their potency. I don't think it is saying that there was no activation of autoreceptors. Looie496 (talk) 17:23, 3 January 2014 (UTC)

Deadly overdose

Is it true that it's impossible to take a deadly overdose? --78.156.109.166 (talk) 20:42, 15 December 2013 (UTC)

No, it is certainly possible. See serotonin syndrome. Looie496 (talk) 17:19, 3 January 2014 (UTC)

Persistent Sexual Dysfunction

I don't object to this being mentioned, even though the sources are all pretty much non-MEDRS. But I am uncomfortable with it being presented as an clinical entity whose existence is widely accepted by mainstream medical practitioners, as it is not mentioned in any medical textbook that I am aware of, and the only "secondary" source supporting its existence is a review written by a member of the University of Iowa group that has written up the majority of the 12 case reports appearing in the literature. Furthermore, this review is published in a non-Medline indexed journal, and authored by a college psychological counselor rather than an established medical expert. Overall, its basically just another primary source. It does not serve the WP:MEDRS purpose of establishing that the subject matter is widely accepted by the mainstream medical community.

I'm also concerned about writing this up in a way that suggests that it is common, given that there are only 12 case reports in the literature from among the 100 million or so who have taken these drugs.

A hard line on this would be to say that since there are no WP:MEDRS compliant sources, this should not be mentioned in the article at all. I won't go that far. But given the lack of mainstream acceptance that this syndrome exists, and the relative rarity persons claiming to have been affected, I think more than a mention that case reports exist is over-emphasis. The language should not suggest that it is common or that the existence of they syndrome is well-established and widely accepted. Formerly 98 (talk) 19:09, 3 February 2014 (UTC)

No compliant sources? Search David Healy and PSSD Yahoo group. The article about PSSD was deleted on January, 23. So you might be happy. Now you can censor this page too and delete this part of this article. Those who are suffering with sexual dysfunction, an there is a huge number of youngsters. Instead of serving the public WeakPedia serves those who finance it. This is everywhere. Nothing new. --Justana (talk) 09:23, 12 February 2014 (UTC)

I'm sorry for your troubles, but advocacy is not Wikipedia's purpose. Material added to articles has to meet the requirements of notability, avoiding excess weight, and in the case of medical information, WP:MEDRS. Yahoo message boards are clearly not MEDRS compliant. Dr. Healy is an interesting minority viewpoint, but a quick look at the APA treatment guidelines will quickly show that his views are far from mainstream. Furthermore, as a paid expert witness in litigation against SSRI manufacturers, he has a very substantial financial COI. Formerly 98 (talk) 14:01, 12 February 2014 (UTC)

"I'm sorry for your troubles." Just now I saw that. I'm a psychoanalyst and in my country, Brazil, and in Argentina psychoanalysis is still strong. You have CBT for everything and a pill for every ill as explained in UK parliament review "The Influence of Pharmaceutical Industry" APA? lol What a joke! APA, FDA... all corrupted. Take a look at the article "evergreening"; You should delete this article. I pity you. Since it is becoming personal I can say I pity you for having to work for the mainstream people. I hope you are being well payed.--Justana (talk) 21:08, 28 February 2014 (UTC)

"...but advocacy is not Wikipedia's purpose." Wikipedia is all about advocacy. It is all about the official view and advocating for the companies, politics and all of those who are... the winners. There are numerous articles with wrong information because it is the mainstream view. I wonder why PSSD had even had an article in this encyclopedia. We know quite well why the article was removed and who told you to remove it. The same people who made "Corporate Crime in the Pharmaceutical Industry" by John Braithwaite disappear from the market by the time it was published. BTW: Iatrogenesis: leading cause of death in US. Search for Dr. Kafka and you'll find your authoritative source for PSSD. We all thought that Wikipedia was a project where people would have a voice. No! It is mainstream, mainstream and once again mainstream. Ergo, no ethics and integrity in this project. Human, all too human. And, please, stop treating those who come here as a bunch of resentful few cases. This is a very serious issue and I'm sure that each of you know someone who had their sexuality altered by an antidepressant. Even among you. It is such a delicate and terrible condition that makes people ashamed of admitting they were chemically castrated. Some people never had and will never have a sexual life because they took these drugs as teenagers or even while childhood. Please, no need to answer with your famous arrogance. --Justana (talk) 00:30, 28 February 2014 (UTC)

Well, I'm sorry you're unhappy. If you want to have it reviewed by another group of people, there are multiple avenues within Wikipedia for doing that. But if you can't get people to agree with you, you can't just force your opinion on everyone else. That wouldn't be giving the people a voice, would it? Formerly 98 (talk) 04:56, 28 February 2014 (UTC)

You are doing consumers who wish to inform themselves a grave disservice. In my original rework, I certainly think I provided enough evidence to state that sexual side effects may persist after using these drugs. It is not that strong of a statement, and readers were free to analyze the evidence for themselves. Now you have removed much of it and left only the case reports.

No article written on the topic is admissible?

Despite thousands of posts by sufferers in the ssriSEX yahoo group and on pssd.forumotion.com, neither is even allowed to be mentioned?

What can be done to present the truth here?

AmiLynch (talk) 00:37, 4 February 2014 (UTC)

I feel quite strongly that we have to followe the MEDRS rules. We can never all agree on what the truth is, but we can agree on what is mainstream opinion. Wikipedia's rules are focused on the latter, more attainable goal.

Rather than further explaim my POV, I'll simply suggest compromise language. After a discussion of the well established sexual side effects that occur during SSRI treatment, I would not be opposed to something like this:

"Symptoms of sexual dysfunction occasionally persist after discontinuation of fluoxetine treatment. The incidence of this adverse effect is unknown. A limited series of published case reports describe loss of libido and/or genital sensation lasting for several years after cessation of therapy"

Can you live with this? — Preceding unsigned comment added by Formerly 98 (talk • contribs) 10:43, 4 February 2014 (UTC)

I was shocked to discover that post ssri sexual dysfunction was removed. I believe I suffer from this and I copied the references cited by Wikipedia. I now feel invalidated and extremely distressed.107.221.229.121 (talk) — Preceding undated comment added 23:54, 26 February 2014 (UTC)

Our articles need to be based on reputable published sources. We can't make use of people's reports of their personal experiences or our articles would degenerate into incoherence. The fact that you feel "invalidated" is not relevant either. Looie496 (talk) 14:50, 27 February 2014 (UTC)

Would this Ph.D. thesis and the supporting docucmentation regarding PSSD be considered "relevant?" 107.221.229.121 (talk) 15:57, 11 June 2014 (UTC)

"...or our articles would degenerate into incoherence." This is a joke. Mainstream views and opinions are dominated by numerous degenerate and incoherent facts, evidences and lack of ethics and integrity. "Invalidated"? You're being quite arrogant saying so but those who have the habit of "contributing" to Wikipedia know the way you mistreat any other view that is not mainstream. I don't have Wikipedia as a reference. We already know how biased this encyclopedia is. The encyclopedia done by the people. Oh, yeah.--Justana (talk) 00:41, 28 February 2014 (UTC)

The alternative to being based on reputable published sources is being based on people's personal opinions. Reputable published sources can be wrong, but people's personal opinions are very likely to be wronger. Looie496 (talk) 15:02, 28 February 2014 (UTC)

The article "Post SSRI Sexual Dysfunction" by Dr. Audrey S. Bahrick, Ph.D. was publishedat page 2 of the volume 7 issue 2, September, 2006 of the ASAP Tablet of by American Society for the Advancement of Pharmacotherapy (ASAP), Division 55 of the American Psychological Association. Maybe Wikipedia do not consider it to be mainstream although the there are psychiatrists who are considered as mainstream by APA - America Psychiatry Association. But Wikipedia has it's own criteria do define mainstream. Anyway, this is the article: Post SSRI Sexual Dysfunction Audrey S. Bahrick, Ph.D.

"Post-market research has now firmly established that the SSRIs and SNRIs can significantly affect most very aspect of sexual functioning at rates significantly higher than the 5-15% reported in pre-market trials. Depending on definitions of sexual dysfunction and methodology, post-market prevalence studies have found rates between 36% and 98%. The 5 to 15% rates of SSRI and SNRI-induced sexual side-effects listed in the current drug-insert literature are based on information obtained in the initial trials via spontaneous reports of individuals who had been on the medications for a short time. The differences in reported rates between the pre-market trials and post-market prevalence studies are an artifact of methodology; we now know that when individuals are directly asked about their experience of sexual side effects via either a structured clinical interview or a self-report inventory, we obtain vastly different rate information than if we rely on individuals to spontaneously volunteer personally sensitive information about changes in sexual functioning."

"The assumption that sexual functioning returns to baseline shortly after cessation of the medications is deeply embedded in our literature as well as in our approach to practice and prescribing. Yet no original data supports this assumption: no study has followed the course of the sexual dysfunction after discontinuation of the medications for the purpose of determining when and to what degree the side effects resolve. While treatment-emergent sexual side effects probably do resolve for most individuals after discontinuing the medications, since we are not even asking the question of whether the side effects could persist for some individuals, we have not built the possibility of finding them into our research designs: at least not intentionally.

"Consumer reported information about persistent sexual side effects comes from the SSRIsex internet community. Founded in January of 2005, SSRIsex now includes a diverse membership of over eight hundred men and women who are struggling with sexual side effects that reportedly began on an SRI/SNRI, but that have persisted months and years after stopping the medications. The group’s purpose is support, the generation of hypotheses about what may have led to the persistent sexual dysfunction side effects, the sharing of information about attempted solutions, and the hope of enlisting researchers and professionals in collaborative efforts to understand and resolve the problem. Along with an ongoing moderated conversation among the membership that now includes over six thousand postings, his well-organized site includes a data base where individuals may describe their case history, and numerous voluntary polls related to particular side effects and their duration, specific medications and how long they were taken, and remedies attempted along with their results. Though the group has not yet been systematically surveyed, based on member postings and informal poll information, it appears that while any and all sexual side effects that start on the medications may continue after stopping them, reduced genital sensitivity, reduced intensity of orgasm, and severely diminished libido are characteristic of the condition which the group membership has termed Post SSRI Sexual Dysfunction (PSSD). It appears that a shared persistent effect of these medications is that they profoundly diminish the physical capacity to experience sexual pleasure. The day to day conversation among the geographically, ethnically and age-diverse-membership related to the problem of living with PSSD, for most a worse condition than the one they originally sought to treat, has created an unfolding collective narrative whose weight and substance urgently needs to be reconciled and integrated into our existing knowledge base."

"We are not negligent as professionals when we turn to our formal literature to inform ourselves. However when our formal knowledge base is inadequate or inaccurate, we are all left vulnerable to practicing in ways that may be less than ideal, to offering hurtful interpretations or misleading information to our clients in spite of our best intentions and best efforts to inform ourselves. The inadequacies and inaccuracies in our knowledge base have complex informed consent implications. A careful informed consent process includes accurate acknowledgment of our limits of knowledge. These limits would appear to be more far-reaching than we may have realized given the possibility of medication-induced sexual dysfunctions persisting for an unknown number of people, and the near impossibility of gaining a clear picture of how these medication may affect those individuals who have no well-established baseline of sexual functioning or are undeveloped sexually, such as adolescents and children."

"The burden and responsibility of providing informed consent falls to us all, but falls even more squarely on the shoulders of those who hold or will hold prescription privileges. I appreciate Division 55’s invitation to contribute this article and demonstrated high level of concern for accurate informed consent." keep reading here. http://apadivision55.homestead.com/vol7no3.pdf Not good enough, we understand and we know that the word of patients and doctors are anecdotal evidence. How can a science consider the object of it's study that can communicate as an object that must be studied without it's participation will be known as something very strange if not nazi in decades to come.

So, how will the fourth phase of clinical trials will be done? Double-bind, oops Double-blind studies? Great! Hilarious! --Justana (talk) 21:59, 20 April 2014 (UTC)

You are being repetitive but I understand that there is no other argument. It is not about people's personal opinions. It is about those scientists, doctors, journalists, lawyers, social scientists, psychologists all these serious people with M.D or PhD who are working hard and with no help, no money to fund their researches because science is in the hands of... guess who? Does Wikipedia has an article about the way science is used? Keep doing what you're already doing: copy from all mainstream sources and censor dissent and the work of those professionals who are fighting for awareness, I'm happy i'm on the side of the solution, not the problem. You on the contrary: help intervention in countries that leads to tortures, genocides, people dying because of iatrogenesis - leading case of death in US -; suicides, homicides. crimes against humanity in general. It would be impossible for me to sleep if I did the kind of work you're doing. I even have a book by mainstream psychiatrist that I could leave here but I'll not do so because it can disappear and it is where people can read and have information. Have a great life and sweet dreams!--Justana (talk) 20:57, 28 February 2014 (UTC)

"Furthermore, as a paid expert witness in litigation against SSRI manufacturers, he has a very substantial financial COI." (about Dr. David Healy) Could you please provide the evidences for such accusation? This is serious and puts Dr. Healy's ethics in question, so, please, produce your evidences. Thank you.--Justana (talk) 15:24, 12 April 2014 (UTC)

How serious of Wikipedia! Put someone's integrity in question without proving. --Justana (talk) 21:59, 20 April 2014 (UTC)

http://www.davidhealy.org.php53-23.dfw1-1.websitetestlink.com/wp-content/uploads/2012/05/2009-Healy-Adolescent-suicide-Canadian-J-Psychiatry1.pdf. See the COI disclosures at the end of the paper. Pointing out a conflict of interest is not an accusation nor is it questioning their integrity. Suggesting that they were writing on behalf of undisclosed third parties, that they are aiding and abetting human rights violations, and fighting to "bury the truth" as you have in multiple places in this thread would be examples of such behavior. Formerly 98 (talk) 20:17, 22 April 2014 (UTC)

removal of sourced content

Regarding the edit summary of this removal of sourced content, please note the paragraph that was removed does not say these 3 critics of SSRI oppose antidepressants. The paragraph that was removed says these critics oppose the view of antidepressants as correcting chemical imbalance because that view is not supported by the evidence. IjonTichy (talk) 01:12, 28 May 2014 (UTC)

@IjonTichyIjonTichy: Good to meet you. I see your point, but if you're going to put this in here, could you at least include some discussion of what they think causes depression? My concerns are:

• Ultimately, depression has to be related to a "chemical imbalance" of some sort, as there are not obvious macroscale structural changes in depression. Either that, or one believes that the brain and the mind are not related to one another. That seems like a stretch to me, but maybe you can fill me in on the theory.
• There is no discussion of WHY they think that the prevailing theory is incorrect. These folks are not such household names that simply saying they disagree with mainstream thought is a very meaningful remark. Could you get a sentence in there at least explaining their reasoning?
• Finally, I think these books and news articles are really primary sources, and not WP:MEDRS compliant.

Let me know what you think. Formerly 98 (talk) 02:04, 28 May 2014 (UTC)