Talk:Selective serotonin reuptake inhibitor

Peranent 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 sumarised, 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)

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

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)

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)