Talk:Sertraline

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Contents 1 Dates 2 Generic Side Effects Versus Name Brand 3 Random Comments 4 Talk 5 Beware of this Editor 5.1 Agreed 6 Obvious Questions 7 suggestion for addition to Sertraline page 8 Dopamine 9 "Evidence against Effectiveness" 10 80 year olds 11 Bioavailibility 12 Medication for childhood experiences? 13 Depressed? 14 Suicide 15 Deleting dopamine claims 16 This sounds like a horrible drug 17 Practice of anonymous edits should be abandoned! 18 Do sertraline more often than TCAs results in continuation of treatment to the point of achieving therapeutic results? 19 Patent(s) 20 Interaction with grapefruit juice 21 GA review 22 other uses 23 Skeletal structure problem 24 Preparing for FAC 24.1 Readability 24.2 Questions 25 Lead 26 FAC discussion 26.1 Sertraline 27 suicidality 28 Synthesis

[edit] Dates

Something is innacurate about this article- it says that Brittain banned zoloft for use in minors in 2003 in one part of the article and 2004 in another. It also says that it was only approved for use in minors in the USA in 2003- This needs to be double checked. --72.19.81.122 02:10, 21 September 2006 (UTC)

[edit] Generic Side Effects Versus Name Brand

Interesting fact: When I last had my prescription renewed by my doctor (a few months ago), she advised me that although there was now a generic for Zoloft available, I shouldn't switch to it unless there's a critical need. She stated that she's experienced with several other patients that the generic does not always have the same effects as the name brand, despite the fact that they should be the same. When I brought this up with my mother, who had recently made the switch to the generic without her doctor advising her of these potential side effects (reducing the potential for suggestion-induced placebo), she confirmed that the effects were not the same when switching to the generic. Additionally, she mentioned that the generic has a different coating, such that it starts melting on the tongue, causing a bad taste as opposed to the name brand of Zoloft. This does not seem to be relegated simply to generic Sertraline, either; I have hearsay evidence that for some people, the generic of Levoxyl (Levothyroxine) functions differently versus the name brand as well.

Another client remarks: I totally agree that the generic 100 mg Sertraline DOES NOT WORK the same as Zoloft. I switch from Zoloft about 2 months ago and have started a down-hill slide towards depression. It wasn't until this morning that it dawned on me when this started. I called my pharmacist and told him I no longer wanted the Sertraline, I want the regular Zoloft because it works for me. Even though I can't really afford the double in price -- what are my options? Suicide is NOT AN OPTION!

This is supposed to be a forum for discussion of the article, not the subject, but that aside... I've heard stuff before about the generic being different from the name brand. www.crazymeds.us/BvsG.html This page at Crazymeds.us, while casual in tone and written by a non-professional, has links to some laws and studies about differences in bioavailability of brand and generic meds (in the US, a generic is allowed to be up to 20% more or less bioavailable than the brand name drug). I think it's important to note that while a brand and a generic may (or may not) be different, it's possible that for some people the generic will work better. Also, for some drugs (sertraline only went off patent recently, so I'm not sure about it) there are multiple manufacturers of generics, so you can try asking your pharmacist if you can switch to a different one. Failing that, I guess you could try a different SSRI that's cheaper (fluoxetine/Prozac and paroxetine/Paxil are both available in generic form in the US), or see if your doctor has samples of Zoloft or another SSRI. Good luck. --Galaxiaad 00:57, 8 February 2007 (UTC)

Hello, I am a long time contributor to wikipedia but this is my first post to a discussion forum as a registered user, so I apologize for not using correct formatting and style etc. My concern in this wiki is the lack of sources behind sources. Are there an experts on the subject that are willing to contribute? —Preceding unsigned comment added by Christopher.hawken (talk • contribs)

There are several people having serious effects from the generic versions of Zoloft (Teva, Greenstone) since taking them. See

http://www.topix.net/forum/business/healthcare/T7R9P0NFHGN871B8J/

[edit] Random Comments

In the section concerning side effects: the part about increased incidence of suicidal thoughts and behaviour being questionable does not seem to be accurate. That data was assembled from double-blind tests where some depressed people (of various degrees of severity) were given Sertraline and others were given placeabos. It was found that while both groups exhibited a higher rate of suicidal behavior / actual suicides than the general population, the group taking Sertraline had a rate of suicide that was higher, and by a statistically significant margin. For this reason, physicians have been urged by the US's FDA to exercise caution when considering the prescription of Sertraline (and indeed all SSRI's) to patients who are exhibiting suicial thought patterns and/or who have a history of attempting and/or threatening to kill themselves (and/or others.) It is not known how or why these patients are apparantly made more suicidal when taking SSRI's, but some people have suggested that it may have to do with the way different individuals metabolize the SSRI's. It does not seem to be the case that a person who has a history of depression but no history of suicidal behaviour becomes more likely to exhibit such behaviours while taking SSRI's. -Random Bloke

Question for Random Bloke: How do you suppose a chemical can put complex thoughts ( commit suicide, write a novel, dance the rhumba, whatever ) into a patient's mind? Considering whether or not that seems possible might lend weight to the answer of whether this is a statistical hiccup or not. FireWeed 23:18, 22 January 2007 (UTC)

I don't think he's saying it can put the thoughts in there; as I understand some of the current thinking, the Sertraline may enable previously-unmotivated folks to act on suicidal thoughts that have been lingering for a long time, unacted upon.

Apart from their self esteem being shot to shit when they read up on the drugs they have become dependent on. No one seems to realise how FUCKING HORRIBLE it is to be on a drug that makes you dizzy, takes away your ability to orgasm, gives you heart palpitations and pins and needles and muscle twitches, but DOESN'T actually make you better. And then when you go off the drug all of it gets worse. And then they tell you it's non-addictive and you're overreacting and you should TAKE MORE. Fuck that! Ragnarokmephy 03:04, 22 January 2007 (UTC)

Have you ever considered that your experience isn't representative? I'm really sorry you have suffered through all this. Josephgrossberg 16:11, 22 January 2007 (UTC)

Yeah. I react pretty badly to this drug. The problem is a lot of doctors are so wrapped up in "man this chemical receives good feedback from Test Group A" they ignore the guy in Test Group B who's still curled in the foetal position listening to Hawthorne Heights. (ew) Ragnarokmephy 05:33, 24 January 2007 (UTC)

Hey, there's plenty of SSRIs out there. Your side effects range from somewhat frequent to infrequent. The most common side effects are worth dealing with at the result of getting rid of the mental disorder, but in your case (more infrequent side effects), you could switch medicines if they're that annoying. The fact that the medicine isn't working alone means you should simply switch (or give it more time, assuming you haven't already). And you really shouldn't let the internet determine your self-esteem when concering the drug (or any drug for that matter), ESPECIALLY Wikipedia. I hope you haven't done this. This article is so negative, it could plant the idea inside someone's head that if they took Zoloft, they'd have a lifelong erection, be vomiting in their sleep, and have a 300% increase of their disorder's symptoms. The article fails to mention that most side effects are INFREQUENT or RARE. I saw one mention of something being "uncommon" (PSSD I think, which obviously is uncommon). I mean, if medicine works, it works...but I'm sure no help comes from a pessimistic attitude. The article sure has hell discouraged me a bit....but not much really (remember, Wikipedia folks!). P.S. Emo definitely won't help. 67.186.151.231 04:53, 28 April 2007 (UTC)

[edit] Talk

How come someone keeps deleting the article in external links that is a full-text medical article on how Zoloft.com provides misleading information? It's on the mechanism of Zoloft how could it be irrelevant, and it's provided as an external link?

it seems that some fans of antidepressants on here are really unwilling to allow critical information to be provided even in external links so that people can make up their own minds and that seems really unfair.

The article is at http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0020392, I keep putting it external links, and it keeps getting zapped. I don't see any reason why this article couldn't be linked to pages for each of the SSRIs that the article mentions as well as for SSRIs in general.

Well, I do. The article addresses the SSRIs as a group. You have been blasting that link onto 20-30 Wikipedia pages. This is annoying and distracting. Please stop. JFW | T@lk 22:29, 20 November 2005 (UTC)

It seems SSRIs tend to attract plenty of arguements because whether or not they work varies from person to person. For many people they can cause a great improvement, for some others, much harm. The details of this have been well studied and documented; in the medical world, both the pros and cons are well known. Of course, some of the people who were not treated well by Sertraline have taken a vendetta against it, and will not rest until the pill has been banned, or everybody has been warned against it. Others, whose mental health was saved by it, will rush to it's defense. Flame warriors: you do not need to change the article to alert the masses The medical community is aware of the risks associated with this and other medications of this type. Just because Medication X ended up making you feel like a zombie does not mean there is a global conspiracy to turn people into zombies. Stop adding to the list of side effects everything that happened to you while taking it. You do not need to add your own scientific discoveries. You snorted Wellbutrin and you think it worked better than swallowing? Great, tell all your Myspace friends, and keep it out of here. People should take benzos if they have too much psychic energy, you say? Gee, somebody better alert the American Psychiatric Association, they still think our brains are made of neurons. Here's a simple guidline to anyone taking it upon themselves to edit a medical article- if you aren't citing a well accepted, peer-reviewed source, you aren't being helpful! --72.19.81.122 06:23, 3 October 2006 (UTC)

[edit] Beware of this Editor

This editor thinks he is a Crusader protecting drug information. What is needed is balanced information, not one editor deleting anything negative about a drug entry which is what this fellow seems to do as well as dissing Wikipedia itself. Yes, he's right about using reliable sources,but the medical community is not always as well informed as it should be, and there are opposing scientific studies presented about particular drugs. When a drug is under a black box alert, it is responsible for knowledgeable editors to provide useful information so that readers are well informed. Since this editor has already proposed elsewhere that readers not use wikipedia as a reliable source for any information on drugs, he should now cease to do ANY editing in that area. There are many very capable editors who are knowledgeable in this area, as in other areas, as shown by the quality of the articles comprising Wikipedia. I recently read a review of Wiki that stated it was of amazing good quality even when compared to known encyclopaedias. It is certainly more up-to-date than printed encyclopaedias that are years out of date by the time they are printed.Any reader who has special interest in a drug can also research this drug through the internet accessing many different resources. I think anyone who does this will likely find that the Wikipedia entries are actually very good. —Preceding unsigned comment added by Szimonsays (talk • contribs)

[edit] Agreed

If somebody doesn't like what they read in Wikipedia, then they're free to get their information elsewhere, and just with the internet the size that it is, there are a lot of resources about literally everything. To my knowledge, Wikipedia is supposed to function as a free, online encyclopedia based on facts, not a single user's opinion, or an engine geared at protecting (or attacking) any certain entity so that said entity can benefit (advertising?) or suffer (mud slinging?). When opinions are presented, they are supposed to be backed up with references/studies/etc in the same fashion World Book or Encyclopædia Britannica would generally go by. Correct me if I'm wrong... jeff (talk) 22:10, 9 June 2008 (UTC)

[edit] Obvious Questions

Who developed it? When? Is it patented? When does the patent expire? Etc.

It is very interesting issue. It seems sertraline is a generic drug, because e.g. Slovenian pharmaceutical company Krka is selling sertraline hydrochloride tablets under trade name Asentra, and Pliva is (or was) selling it even under the name Sertraline. But there is Pfizer's patent on sertraline which expires in December 2005, and there is another sertraline patent which expires in 2010... I'm confused. Maybe it has something to do with polymorphism. Mykhal 21:51, 30 Oct 2004 (UTC)

in australia, all of the tablets are the same colour, white

• here in Europe, too -Arny 02:13, 18 April 2006 (UTC)

[edit] suggestion for addition to Sertraline page

The adverse effects listing in the third paragraph omits a major one: sexual side effects, which is a major complaint with most of the SSRIs.

• Done. Eldereft

BTW, Canada also sells Sertraline (generic) in 50- and 100-mg capsules. The patents must apply on a country by country basis.

Another side effect is a tightness/discomfort in the throat; which can be a symptom of increased anxiety.

The adverse effects listing in the third paragraph omits a minor one: increased sweating. I use the drug and since then this has subsided, but in the sheets the pharmacy gave me along with sertraline "increased sweating" is listed. From personal experience (I am unsure who should be credited with this info; it is reported on various websites as well), during the "insomnia" phase while my body was adapting to its use (apparently), I would wake up very sweaty, from the first night I took it and decreasing afterward.

Setraline is sold in Australia, like it says, but in only white tablets. A few different generic names for it here like Concorz from Hexal, but you can of course get Zoloft itself. Pfizer sends Zoloft trial packs to doctors to give to patients, in the hope that the patient will want to continue using the same brand.

Another theory about the correlating suicide rate with antidepressant usage is that users feel the drugs were unsuccessful at curing their depression, and extrapolated that into there being "no" cure.

Why not post information about a less talked about side effect, "smelly farts"

[edit] Dopamine

It is mentioned in the article that sertraline also works on dopamin in high doses. So far I haven't found any source to confirm it, although I accept it is probably true since I've already heard that before. However, there should be a citation or link or something to confirm that. Arny 02:17, 18 April 2006 (UTC) P.S. And how high are those "high" doses? Some milligrams would be informative here...

• Ok, I've finally found a medical article with some info about this and will add it to the article. --Arny 14:59, 1 May 2006 (UTC)

[edit] "Evidence against Effectiveness"

This cites just one study and completely neglects the countless other studies which have shown Zoloft to be an extremely effective medication for the treatment of depression. It is a first-line SSRI that is often used before any others for treating typical depression, in most psychiatric units. The "Evidence against Effectiveness" section sends a very bad and misleading message. It should be changed or removed completely. --Muugokszhiion 18:59, 22 July 2006 (UTC)

To be fair, it seems to me it's a first-line antidepressant because of its relative lack of side effects and probably marketing too. However, I mostly agree: having a separate section for this one study, and none describing studies that support its effectiveness is misleading. Maybe we could change the section to "Studies of effectiveness" and include more. --Galaxiaad 19:38, 22 July 2006 (UTC)

I'm commenting (hiding) the section until more NPOV sources can be added. Since Zoloft (along with the rest of the SSRIs) has been shown to be highly efficacious in the treatment of major depressive disorder, it is important that studies proving its effectiveness be shown as well. Otherwise, the section is very POV. Furthermore, the title should indeed be changed to something more neutral, such as Galaxiaad's suggestion, "Studies of effectiveness." --Muugokszhiion 18:52, 19 September 2006 (UTC)

To be honest, my boyfirend is just on that shit, and as far as I can see... it's only about the people being so sick that they can't be bothered to think about being in a bad mental state. I dunnu if it "works"... I mean if it's proved, but what I know is that making a pretty healthy normal person that just collapsed out of stress into a all-time-sleeping, shaking, throwing up wreck is WIERD... I hope the doctors know what they're doing. Peace.

[edit] 80 year olds

What's with the line about 80 year olds in the first paragraph? Should it be removed?

[edit] Bioavailibility

I noticed that the bioavailibility percentage went from 95% to ~45% just recently. Do we have a source for this change?

Also, I've found several sources claiming that taking sertraline with food increases the bioavailibility (http://psyplexus.com/pt/index.php/2004/10/24/increasing_the_bioavailability_of_sertra), and another that claims taking it with food has no effect (http://emc.medicines.org.uk/emc/assets/c/html/displaydoc.asp?documentid=18935).

[edit] Medication for childhood experiences?

It seems a lot of research is being done to prove the effectiveness of anti-depressants such as Zoloft. But why, after so many years since the drugs first release to the public, are results still inconclusive? Pfizer’s own Zoloft official web site (www.Zoloft.com) states in every page the risk of increased suicidal rates in children under the age of eighteen is doubled when taking antidepressants. Yet, in another article entitled, “Zoloft Effectiveness in Childhood depression” by Sid Kirchheimer, a study comparing the effects of Zoloft with placebo showed that while 69% of patients taking Zoloft had improved symptoms, 59% of the patients taking placebos also improved their symptoms. Is this a significant enough difference to say that Zoloft is effective? The FDA, based on the data submitted to them by antidepressant drug companies, disagrees. However, “placebo response is very high in short-term studies like this one” comments the researchers Karen Dineen Wagner, MD, PhD, and Clarence Ross Miller Professor and vice chairwoman of psychiatry and behavioral sciences at the University of Texas Medical Branch in Galveston. Their research, funded by Pfizer, was for the duration of only ten weeks. Both agree that further research is needed to make a clear decision in prescribing it to children. In a more recent study by Gregory E. Simon (American Journal of Psychiatry, January 2006; vol 163: pp 1-7.) Suicide rates showed a decline in both adults and children after a six-month period. The risk of suicide rates remained high in the first months of treatment. This study included mostly adults, however. Although child depression is a serious subject, perhaps antidepressants aren’t the solution. Part of being a kid is having the resilience to grow up and overcome certain obstacles that may or may not contribute to depression. If placebo pills can show an improvement in symptoms of children, perhaps doctors shouldn’t “jump the gun” on prescribing antidepressants to them. That is not to say that antidepressants aren’t effective, but that to express extreme caution when dealing with children under the age of 18 until further research has been done to finally put an end to the ongoing debate about the side effect increasing the risk of suicide rates in kids. Perhaps an understanding of the causes of depression in today’s younger generation can provide insightful reasons in determining whether their condition can be helped by antidepressants or if the depression is a normal part of life. Are we creating a need to medicalize normal human experience?

[edit] Depressed?

While depression and anxiety disorders are now generally viewed as viable diseases, I wonder how it would have been preceived in the past if it were medicated. As a society, we give everything a name and call it illness as soon as it causes discomfort. Don't get me wrong, I believe that being depressed can severely limit your ability to live life the way you want. But drugs like Zoloft are pushed so hard to consumers that many times people are misdiagnosed and mistreated. The commercials and websites that publicize Zoloft are aimed at people who feel bad about themselves. They are the people who are more likely to buy into a disease whether or not they have it or not. Big drug companies are usually the ones that market these drugs because their name has power in the minds of consumers. They even encourage us to diagnose not only ourselves, but others if we care enough about them. How can we diagnose a disease who's symptoms can be considered to be a swing of a mood? When can we find a better way of diagnosing depression and other likewise diseases?

--I agree that people should not seek medication because of a "swing of a mood." Serious depression is far more than a mood swing -- it is an utterly debilitating and sometimes life-threatening condition. I didn't start taking Zoloft because of an ad; I started taking it so I wouldn't kill myself. And guess what? It works for me, and not because of some placebo effect, as I had never heard of it before and was skeptical that it would work in the first place.

Your questions are valid; I'm just giving you my take on it. 71.192.117.240 02:33, 19 December 2006 (UTC)Greg

I would agree that medication should not be marketed directly to the consumer. In fact I think it's almost criminal for a pharmacology company to encourage niave individuals to diagnoss themselves and others. Be that as it may, depression is more than a "viable disease," and people who suffer from it ( in the medical sense - not as a mood ) deserve the best treatment science can find. FireWeed 23:15, 22 January 2007 (UTC)

[edit] Suicide

This is common amongst all anti-depressant treatments, including ones that are not SSRI-based, and even non-drug treatments ( ie talk therapy ). Many who are depressed describe a lack of "mental energy." These individuals recognize things they could/should be doing to improve their condition, but can't actually carry the task out. ( Excersize is among the best treatments for depression, but (catch 22) you can't get a depressed person to excersize. )

It's a very small logical leap to assume some individuals with major depression symptoms have often contemplated suicide, but, like with excersize, simply do nothing, caught in the depths of their depression. When this type of patient, determined but unable to commit suicide, begins treatment, when their "heavy fog" begins to clear, the worst cases are still suicidal, suddenly find the wherewithall to carry out their long-standing wish.

In fact doctors ( either psychologists or family practicioners ) are alert for early signs of manic happiness in patients who had been morbidly depressed, as this is often an indicator that the patient is considering something rash. FireWeed 23:11, 22 January 2007 (UTC)

[edit] Deleting dopamine claims

Disclaimer: I'm not a pharmacologist.

The article currently says:

"Sertraline appears also to be a minor dopamine reuptake inhibitor. Dopamine is responsible for the 'feeling rewarded' feeling in the brain (as well as being heavily involved in coordination of voluntary movements). While feeling reward generally leaves the user of the drug feeling great, it is not the intent of the drug."

Which seems to imply that sertraline is directly rewarding/reinforcing. AFAIK, for dopamine reuptake inhibtors to be reinforcing, the effect needs to be fast and strong. Sertraline is neither, as it takes more than 4 hours to reach maximum concentrations and it is much stronger as a SRI than DRI. In any case, a citation would be needed.

The article also says

"Interestingly, since activities like smoking cigarettes increases dopamine levels in the brain, some smokers actually have increased cravings while on SSRI drugs."

The relation between these statements is unclear. Is it that dopamine reuptake inhbition increases the effects of smoking? But why does it mention SSRIs in general then (the other SSRIs are not DRIs)? Or is the point that SSRIs indirectly inhibit dopamine and cause cigarette craving? Please clarify.

The section has apparently been tagged since February, so I'm removing those claims and (while I'm at it) turning the section into a "mechanism of action" section. Experts, please improve it :)

84.58.135.53 12:20, 13 May 2007 (UTC)

[edit] This sounds like a horrible drug

Maybe someone should list some of the positive effects of Zoloft? --76.185.57.166 20:15, 1 June 2007 (UTC)

Am I the only person that finds the overall tone of the article positive? - Me —Preceding unsigned comment added by 71.224.15.12 (talk) 04:47, 9 January 2008 (UTC)

[edit] Practice of anonymous edits should be abandoned!

The Billy Dzomba and Steve Verner hoax has been on the Zoloft Wikipedia page for several months and propagated across thousands of internet pages including answers.com. It is clear that anonymous (IP address) edits are the source of majority of the vandalism and unsourced information. Allowing them may have made sense in the beginning of Wikipedia to attract more editors, but this practice can probably be safety abandoned now. I wonder if there are more people thinking so. Is there any kind of page that discusses this issue in Wikipedia?Paul gene 11:05, 3 July 2007 (UTC)

Yes—it's been discussed at length and rejected every time: please see Wikipedia:Disabling edits by unregistered users and stricter registration requirement and meta:Anonymous users should not be allowed to edit articles. Fvasconcellos (t·c) 11:49, 3 July 2007 (UTC)

I was wrong about Wikipedia having enough editors. Or to be more precise, there are too many editors but not enough contributors.Paul gene 13:08, 25 August 2007 (UTC)

I have to disagree with Paul. IMHO, the bottleneck for the improvement of Wikipedia is the adding of new information, not the deleting of vandalism. I think 1 good anonymous contribution more than offsets 100 anonymous vandalisms, which are easily reverted.

WP:Reliable Sources guidelines state:" Jimmy Wales has said it is better to have no information at all than to include speculation, and has emphasized the need for sensitivity: I can NOT emphasize this enough. There seems to be a terrible bias among some editors that some sort of random speculative 'I heard it somewhere' pseudo information is to be tagged with a 'needs a cite' tag. Wrong. It should be removed, aggressively, unless it can be sourced." Most of WP editors do not remember that.Paul gene 13:08, 25 August 2007 (UTC)

As for hoaxes like the one you mention, that are not obvious vandalism: Disabling anonymous edits won't stop that. If a vandal has the time to think up a believable hoax, he has the time to register. Suboptimal Username 14:08, 18 August 2007 (UTC)

Yes, all I want them is to register. Would help to control them - think analogy with prostitution and drugs of abuse.Paul gene 13:08, 25 August 2007 (UTC)

[edit] Do sertraline more often than TCAs results in continuation of treatment to the point of achieving therapeutic results?

Hga made a correction to the statement: Sertraline has a similar effect on the core depressive symptoms to the tricyclic antidepressants (TCAs) but because of the lower rate of the side effects sertraline treatment often results in a better quality of life.

After the correction the statement reads: Sertraline has a similar effect on core depressive symptoms as the tricyclic antidepressants (TCAs) but like other SSRIs has more tolerable side effects, which more often results in continuation of treatment to the point of achieving therapeutic results and in a better quality of life.

Hga also commented: "Improvement to addition; I've always read that low side effects before results was the greatest advantage of SSRIs. TCAs are nasty..."

Hga improved the style nicely but I beg to disagree with the meaning of one part: "which more often results in continuation of treatment to the point of achieving therapeutic results". What Hga appears to say is "the drop off because of the side effects of the SSRI therapy is lower than for the TCA therapy". That is not always true: there are nasty SSRIs, for example, paroxetine and nicer TCAs, for example, nortriptyline. So, when sertraline was compared with nortriptyline, the rate of therapy discontinuation because of the side effects was the same. (see Comparison of Sertraline and Nortriptyline in the Treatment of Major Depressive Disorder in Late Life. Am J Psychiatry 157:5, May 2000).Paul gene 22:53, 4 August 2007 (UTC)

Ah. I've read what I added (although I'd have to dig up a proper source to support it), and I know from personal experience that imipramine (the previous "gold standard") is nasty ("I have to be truly depressed to put myself on it" :-), that paroxetine can trigger drug induced mania, and that escitalopram (the narrowest in effect SSRI) can be well tolerated.

If we compare "gold standard" versions of the drugs, my addition was probably correct. But if we select for lower side effect versions in the respective TCA and SSRI families (as any good practitioner should), I'm quite willing to believe there isn't such a stark difference, or any difference to speak of, as that study indicates. Although, Tricyclic_antidepressant agrees with my general point, and makes a better one that the TCAs are more toxic in excess and therefore more dangerous if used in a suicide attempt.

To properly close this off, we should probably see if we can find a study comparing the side effects of imipramine to nortriptyline, or we could search for one or more of the inevitable review articles that compare the TCA and SSRI families. And then we should amend the various articles like the TCA one to amplify on this point. Anyone is welcome to "be bold", I don't have time for a while. Hga 11:13, 5 August 2007 (UTC)

[edit] Patent(s)

I believe the patent referred in the History section is only in reference to the US patent. Should this be clarified? 24.226.115.176 19:26, 13 August 2007 (UTC)

[edit] Interaction with grapefruit juice

I deleted the study on interaction of grapefruit juice with sertraline because most likely it is invalid. Five elderly people (63-74 y/o) participated. Four of them were taking multiple other medications. In two out of five subjects no changes in sertraline level was observed. The other three got double increase in the through concentration of sertraline. The indications of limited validity of this study: it was small, sick elderly people are not representative of the general depressed population, they were taking other medications making possible that the grapefruit juice increased concentration of the other medication, which in turn increased concentration of sertraline. It is also known that grapefruit juice inhibits CYP3A4 enzyme, while the enzyme responsible for the majority of sertraline metabolism is CYP2B6. CYP3A4 only responsible for ~15% of sertraline metabolism, so it is unclear how its inhibition could increase the sertraline concentration two-fold. Paul gene 01:05, 6 October 2007 (UTC)

[edit] GA review

OK - I will add notes here: cheers, Casliber (talk · contribs) 00:28, 18 January 2008 (UTC)

The most active (+)-cis-isomer was taken into further development and eventually became sertraline. - 'become' sounds like it changed into it or something. Another verb or phrase might be clearer. 'was named'? cheers, Casliber (talk · contribs) 00:30, 18 January 2008 (UTC)Y Done

For example, similar improvement of depression scores was in comparative studies - need a 'seen' after the 'was'? cheers, Casliber (talk · contribs) 00:32, 18 January 2008 (UTC)Y Done

I passed the article as it easily fulfils criteria and the above two issues are very readily fixed. I found the prose easy but then again I am a psychiatrist so I may have missed some jargonistic expressions or words that others may find issue with.

Now onto FAC: I have this idea that Wikipedia can do information more comprehensively and better than much that we've seen before and I may be a bit ambitious in this but I thnk it is possible here. I'll explain:

• For true comprehensiveness I think a history of market share since introduction is important. I recall fluoxetine came out, followed by sertraline and paroxetine, with the latter falling away in popularity in Australia anyway. Later on came fluvoxamine, citalopram and finally escitalopram. it wuld be great to expand a little on the competition over the past 15 years.Casliber (talk · contribs) 00:53, 18 January 2008 (UTC)

I tried to read on this but the market share of different antidepressants and competition between them vary widely among countries. Unfortunately, there is no lesson to learn from that information. You can read about it here [1] and here PMID 15462638 Paul Gene (talk) 02:11, 19 February 2008 (UTC) Y Done

• Also I do recall some issue with some in the field promoting the view that TCAs were superior in melancholia, so addressing this would be good.Y Done

• Expanding on the other sections, the use of SSRIs is significant in people with personality disorder and there is some biochemical basis for this. It needn't be very long but the other uses section as is is a bit listy and meagre.Casliber (talk · contribs) 00:53, 18 January 2008 (UTC)

One open label study on 11 patients with personality disorders was conducted and I do not think it deserves mentioning. Another large study on depressed patients with co-morbid personality disorders did not have a placebo control, but I mentioned it. There have been no other studies on sertraline for personality disorders, so talking about it more would have given it undue weight. Paul Gene (talk) 01:06, 24 March 2008 (UTC) Y Done

• change 'sertraline patients' to 'patients on sertraline' I think.Y Done

• There needs to be a list of various names used in different countries Casliber (talk · contribs) 00:53, 18 January 2008 (UTC)

No, WP:MEDMOS discourages the mentions of brand names, except for the one-two the original manufacturer has used. However, I provided the link to Merck manual where many international names are mentioned. Paul Gene (talk) 00:36, 26 February 2008 (UTC)Y Done

• there is an issue with many trials of antidepressants in that many exclude people who have suicidal ideation. Unfortuantely this differs markedly from many hospitals where many people have suicidal ideation. As the effectiveness of antidepressants seems to increase with more severe depression this is one of the reasons cited that effect sizes seem small. I've heard this a few times but I am not sure where it has been published as such.Casliber (talk · contribs) 00:53, 18 January 2008 (UTC)

It appears that sertraline's efficacy is independent or weakly dependent on the depression severity, in line with results of different meta-analyses of antidepressants. I addressed this issue in several places. No studies has been done on actively suicidal patients, even in the trials on inpatients they were excluded. Paul Gene (talk) 22:12, 23 March 2008 (UTC)Y Done

• Fianlly I'd get a lay-person to read it and copyedit before FAC

I'll keep in touch and see how it's developing. Congrats. cheers, Casliber (talk · contribs) 00:53, 18 January 2008 (UTC)

[edit] other uses

why doesnt it say anything about doctors using it with kids with adhd and asd?--The Last Uchiha 10:00, 7 February 2008 (UTC)

[edit] Skeletal structure problem

On the skeletal structure and the ball-and-stick model of the molecule, there are two chlorine atoms, but in the info table, the formula is C₁₇H₁₇N (no chlorine present). Which one is correct? —Preceding unsigned comment added by 72.175.41.175 (talk) 03:24, 25 March 2008 (UTC)

The structures are correct. The chlorine atoms must have been removed from the drugbox; the molecular weight still matched C₁₇H₁₇Cl₂N. I've added them back, thanks for noticing. Fvasconcellos (t·c) 16:47, 25 March 2008 (UTC)

[edit] Preparing for FAC

OK then, I am reading a book by David Healy which may be very useful in providing some reliable sources for the background and criticisms. The main thing as the article should not merely resemble a product information page. Cheers, Casliber (talk · contribs) 00:25, 20 April 2008 (UTC)

OK, before copyediting we need to make sure nothing notable has been left out and everything is referenced - every paragraph should have at least one reference:

• Para 1 of History needs some refs at the bottom of it. Also nthing about the development of it before approval but I may be able to help out there.

Gotta go now. more later. Cheers, Casliber (talk · contribs) 00:25, 20 April 2008 (UTC)

On second thoughts looking better than I thought. We aren't too far away. I can't do much until tonigh though (Sydney time). Cheers, Casliber (talk · contribs) 00:34, 20 April 2008 (UTC)

I moved the relevant references from the beginning to the end of the first paragraph of the History. This paragraph talks about the development before the approval. I hope I researched and referenced the article exhaustively; I am rather afraid that there will be complaints that it is too detailed, and there are too many references. Paul Gene (talk) 00:48, 20 April 2008 (UTC)

Don't worry, I am getting familiar with the process now after 16 FAs. It isn't too detailed and this book may provide some more social context. Copyediting will trim a bit too. Cheers, Casliber (talk · contribs) 01:01, 20 April 2008 (UTC)

Which Healy book are you referring to? I have most of them. He usually talks about SSRIs/antidepressants in general, so this may not be applicable to specifically sertraline. He is also sometimes wrong. As far as I remember, the only particular antidepressant he discussed at length is fluoxetine, but then it could be that I am missing something, since I read some of those books more than a couple years ago. Paul Gene (talk) 10:16, 20 April 2008 (UTC)

You're right, it is The Antidepressant Era and only mentions it twice, though does give UK release date which will help this article to be less US-centric..Cheers, Casliber (talk · contribs) 05:11, 21 April 2008 (UTC)

• In the first bit of the Indications section, is it worth pointing out these are worldwide? Cheers, Casliber (talk · contribs) 09:10, 20 April 2008 (UTC)

I do not know, I used the FDA-approved indications. Paul Gene (talk) 10:17, 20 April 2008 (UTC)

[edit] Readability

Given that you and I may lapse into jargon without realising it, it would be good to get a layperson to have a look. I will try and find someone. Cheers, Casliber (talk · contribs) 05:17, 21 April 2008 (UTC)

Oops. first try didn't work so well...Cheers, Casliber (talk · contribs) 14:35, 22 April 2008 (UTC)

I asked Galaxiaad, who is a pharmacist, and FVasconcellos, who is not an MD or pharmacy professional (my guess, which could be wrong), to look at the article. They did a lot of copyediting but did not seem to find any major problems. I intentionally divided the article into many sub-chapters so that the lay reader could jump to the part he is interested in. Paul Gene (talk) 00:14, 24 April 2008 (UTC)

Oops, I'm just a pharmacy tech. ;) So I do have pharmacy experience but haven't gotten farther than gen chem and bio in school so far. I only got partway through the article so I'll try and finish my copyediting tonight. I also had a couple places that are unclear to me, which I was going to ask about on here... sorry I've taken so long! --Galaxiaad (talk) 03:22, 24 April 2008 (UTC)

Will finish up tomorrow. --Galaxiaad (talk) 06:11, 24 April 2008 (UTC)

[edit] Questions

These aren't necessarily things I think should be changed. They're just things that weren't totally clear to me.

The original pre-marketing clinical trials demonstrated only moderate efficacy of sertraline for depression. Nevertheless, later research firmly established sertraline as one of the drugs of choice for the treatment of depression in outpatients.

Does this mean later trials showed it was more effective than earlier ones suggested? Or just that the SSRIs have less side effects than the TCAs and so superseded them?

Are there any meta-analyses or big trials of just efficacy vs. placebo? All I really see is "more effective than placebo" and "equally effective as TCAs and better tolerated". But how much more effective than placebo? What's "moderate efficacy"? What I guess I mean is it'd be helpful to the lay reader to see what percent of depressed patients respond (as compared to placebo). But I do see the problem in coming up with one number for this.

Patients on sertraline also reported significantly better social and physical functioning. The patients who achieved a remission during the trial (30% of the sample) did not differ from the healthy population on the measures of marital, parental, physical and work functioning and were close to normal on social adjustment and other measures of interpersonal functioning.

I can't find the full-text article to check--does the 2nd sentence refer to only the sertraline patients, and only after treatment?

At the same time, sexual desire and overall satisfaction with sex stayed the same, as in the beginning of the sertraline treatment, and slightly below the placebo.

Can't see the full text on this one either. Does this mean desire and satisfaction stayed the same as they were before treatment in the sertraline group, and increased slightly in the placebo group?

In addition to decreasing the frequency of panic attacks by about 80% and decreasing general anxiety, sertraline resulted in improvement of quality of life on most parameters, in contrast with the placebo, which did not improve the quality of life as much even among the patients who apparently responded to it.

I'm just having trouble with the phrasing here: "improvement of quality of life on most parameters, in contrast with the placebo" makes it sound like it didn't improve with placebo, but it did, just not *as much*. I can't think of a better way to phrase it.

That's it. I'm really impressed by this and all the work you've done, Paul Gene. --Galaxiaad (talk) 07:36, 25 April 2008 (UTC)

• The original pre-marketing clinical trials... I added reference to a meta-analysis of pre-marketing clinical trials and corrected the wording to weak-to-moderate. Weak is effect size 0.2, moderate - 0.5. Sertraline has 0.26 according to the quoted paper. Percent-wise difference is hard to pinpoint because of the different size of placebo effect and the measures used (response, remission, improvement, significant improvement). The problem with the double-blind design is that even the patients on the active medication do not know what they are taking. In the actual practice, the patient always knows that he is getting active medication, so it adds additional non-specific (placebo) effect. For example, if all of the patients in a certain practice are just assigned to sertraline, thus avoiding prescription bias but not blinding them, sertraline shows stellar results (with more than 70% of the patients improved). Then again, that trial was financed by Pfizer. The effect size in the later double-blind trials is almost certainly higher, which could be due to the both Pfizer learning to ask the right questions and select the right patients and the publication bias.

Sertraline superseded TCAs mostly because of the fewer side effects. It is used more than other SSRI's in the US probably due to the Pfizer marketing might. There are no objective differences between sertraline and escitalopram. Sertraline may be more effective than fluoxetine in some patients, and it certainly has milder withdrawal syndrome and cognitive side effects than paroxetine. Do you think that should be mentioned in the lead, or the corresponding comparison part reworked completely? I would appreciate your help. Paul Gene (talk) 11:11, 25 April 2008 (UTC)

Thanks for the responses. I'm definitely in the dark about most of the clinical-trial stuff (now not quite so much!) But I like the new lead. I think it'd be good if others weighed in (on the new changes, I mean)... but I guess that'll happen at FAC anyway. :) --Galaxiaad (talk) 05:34, 26 April 2008 (UTC)

[edit] Lead

The article looks really good (although pls ask User:Brighterorange to run through and fix the dashes, and please check for remaining unlinked dates in the citations). But, the lead doesn't seem to be an adequate summary of the article (see WP:LEAD). It scarcely touches upon Indications, most of Adverse effects, and Controversy. The lead should hit all highpoints, all significant controversies, and provide a stand-alone summary of the entire article; it's not doing that. As a layperson, I already know a lot more about zoloft than the lead is telling me. SandyGeorgia (Talk) 03:54, 27 April 2008 (UTC)

• Added more material to the lead, and thank you, Galaxiaad for fixing the redundant refs, dates and dashes. Paul Gene (talk) 11:13, 27 April 2008 (UTC)

Also, you might want to work this in to the pediatric OCD info: PMID 17241830 Also, the article doesn't seem to deal with trichotillomania. I don't know that much about it, but I found this: PMID 16889452 I'm not sure that's worthy of inclusion, but the info on treatment of OCD with comorbid tics or Tourette syndrome does need to be mentioned, as zoloft treatment is common. Also, my (British journal) sources list an additional name: Gladem. That's from Robertson MM. "Tourette syndrome, associated conditions and the complexities of treatment" (PDF). Brain. 2000;123 Pt 3:425–62. PMID 10686169 SandyGeorgia (Talk) 04:13, 27 April 2008 (UTC)

• PMID 17241830 is a poor quality paper. The liberal use of statistics (Quote: "The post-treatment CY-BOCS score mean (SD) for patients without a tic disorder was slightly lower with (15.5 (5.3)) than without (17.0 (5.6)) a tic disorder, but the main effect of tic disorder was not statistically significant (Wald X2 = 1.21, p < .05) where the tic disorder treatment interaction term was statistically significant (X2 = 12.32, p < .006).") obscures a simple fact that the authors studied a small sub-group of 15 children from a larger trial. They compared them on several factors, and even though one of them appeared to reach statistical significance, this result by no means can be considered reliable. Paul Gene (talk) 11:28, 27 April 2008 (UTC)
• PMID 16889452 is another bungled study. 40% (16 out of 42) subjects including all but two (!) placebo patients dropped out. Most of the changes were not statistically significant. Paul Gene (talk) 11:47, 27 April 2008 (UTC)
• Gladem. The lists of international brand names is an unnecessary trivia. But at the end of the article I provided a link to the reliable list of international names for sertraline from The Merck Manual. Paul Gene (talk) 11:58, 27 April 2008 (UTC)
• Tourette. Added.

Citations in the Lead Copying from a discussion on my Talk page [2]:

There is no exception to citation requirements for the lead. Leads are often pretty general, so sometimes it's not practical to cite a general statement which is broken down and cited more specifically later in the article. A statement like the one in question is very specific, and there is no reason to exempt from the obvious need for a citation.

A few additional comments.

• The statement is very specific, which is why it should be cited, and perhaps also why it doesn't really need to be in the lead. The lead is for a general overview of the topic, not descriptions of which treatments surpass others in what combination. The claim seems to have just two sources, which doesn't merit being stated as fact. Is it a majority view in the field that CBT is superior?
• Good article! Congratulations to the editors. I've said my 2 cents on this very minor point, so I won't make the edit again. Life.temp (talk) 02:59, 7 June 2008 (UTC)

[edit] FAC discussion

[edit] suicidality

can we change the word for suicide (ie: rate of suicide) ? I am not sure that the word (suicidality) exists in english, and if does, it should not... —Preceding unsigned comment added by 65.4.91.165 (talk) 02:03, 6 June 2008 (UTC)

It exists in the medical jargon, but it's nearly unknown outside of it. I agree that a term like "suicide rate" (if this is indeed what's meant?) would be clearer to more people. --Delirium (talk) 02:47, 6 June 2008 (UTC)

Suicidality and suicide rates are not (necessarily) the same. While suicidality encompasses a broader spectrum of suicide-related issues, such as suicidal ideations, tentaminis suicidii, suicidal crisis, parasuicides and completed suicides, suicide rates are only quantifications of some of these phenomena (mostly tentamini and completed suicides) in groups of people/patients studied.--84.163.108.240 (talk) 02:57, 6 June 2008 (UTC)

The word was coined by the FDA to describe the total of the above phenomena. It is a legitimate word and it with time it will make it to the official dictionaries. Albeit it may sound awkward, the general reader should have no problems understanding it — suicide+ity. Paul Gene (talk) 09:24, 6 June 2008 (UTC)

I'm a little bit more than a general reader -- I've read about this issue of suicides in Science and NEJM -- and I have problems understanding it. (I think it's a composite of suicides, suicide attempts, and suicidal ideation). It's not a word a general reader could understand. If it's not in the dictionary, it's a neologism or jargon term, which violates WP:WTA. If you use it in the entry, you have to define it first.

The important point (in my understanding) is that there is no high-quality evidence that any of the antidepressants cause suicide, because of the low power, low numbers, and short duration of antidepressant studies, so they use suicidality as a surrogate end point. But, as the NEJM always says, surrogate endpoints are often wrong (like the surrogate end point of blood loss instead of mortality in the aprotnin study, 358:2398). So while there is evidence for "suicidality", which may or may not turn out to be an artifact, there's no high-quality evidence for increased suicides, and SSRIs may or may not cause increased suicides. Nobody knows at the usual standards of scientific certainty. I think the entry should make it clear.

BTW the Cochrane Collaboration [3] doesn't use the term "suicidality" at all, they say "suicidal ideation and attempts", which is what I think we should use. They say:

There is evidence that those prescribed SSRIs are at an increased risk of suicidal ideation and attempts (RR 1.80, 95% CI 1.19 to 2.72) consistent with a number of similar reviews in the area. Additionally, there was an increased risk of other adverse events. It is unclear how this relates to the risk of suicide completion. The trials were not designed to measure any of the suicide related outcomes adequately. At the same time, untreated depression is associated with the risk of completed suicide and impacts on academic and social functioning, however, it is not clear whether treatment with an SSRI will modify this risk in a clinically meaningful way for children and young people.

I think you should read the whole Cochrane entry for a good discussion of the issues. Nbauman (talk) 01:59, 9 June 2008 (UTC)

[edit] Synthesis

Is it Ok to include the synthesis of the compound into the article? The sythesis is interestin and includes a enantioselective step at the end in which only the desired enatiomere is formed. Normaly the pharmacetical industry starts with compounds from the chiral pool to do this.George J. Quallich (2004). "Development of the commercial process for Zoloft/sertraline". Chirality 17 (S1 Special Issue: Proceedings from the Sixteenth International Symposium on Chirality): S120 - S126. doi:10.1002/chir.20113. --Stone (talk) 06:31, 6 June 2008 (UTC)

This issue was discussed during the FA nomination. I believe that synthesis of sertraline is of little interest even for specialists, and of no interest whatsoever to the general reader. Paul Gene (talk) 09:20, 6 June 2008 (UTC)

agree - synthesis is of interest only to specialist.HOWEVER, the point that sertraline is chiral (one enantiomer) could be of interest re side effects (eg the side effects of thalidomide are due to one enantiomer, the other is actually useful for something). However, untill there is some clinical evidence on this point, it can be left outCinnamon colbert (talk) 12:57, 6 June 2008 (UTC)

1. It's one diastereomer (enantiomer pair) of sertraline isomers, 2. thalidomide enantiomers are undergoing racemization in vivo each, so that after all, racemate and both enantiomers are teratogenic (it is used as an adjunctive antileprotic, given that effective contraception is provided during the treatment).--84.163.108.240 (talk) 13:03, 6 June 2008 (UTC)

I am not sure wether this answer is meant to be misleading or not, but there is not mention of synthesis in the FAC. Anyways I find your statement " synthesis of sertraline is of little interest even for specialists" to be at least apalling. I am not sure how much you have interacted with true specialists, but your view on this topic is really limited. I am not going to spend minutes arguing how Sertraline is first of all a chemical and then a drug. Even if it were, the article should have at least a link to a sub-article presenting synthesis reported in academic literature and if available, the comerical one too. Nergaal (talk) 10:24, 6 June 2008 (UTC)

Where exactly in the FAC was this stated?--Stone (talk) 21:13, 6 June 2008 (UTC)

The sythesis might be as interesting as Pharmacokinetics for most of the people! So the synthesis should be a small section mentioning the first synthesis and the now used synthesis which is considerable more easy. --Stone (talk) 21:13, 6 June 2008 (UTC)

There is a reference to the first synthesis of sertraline in the article—it is the review of sertraline development by Welch. The journal = Chirality synthesis does not look that much easier to me. Paul Gene (talk) 09:28, 7 June 2008 (UTC)