Talk:Paroxetine

Links

I don't think "official" should be used in "The official paroxetine site" link (paroxetine.com). How is it "official"?

• The content is nothing special-- and nothing that can't be found elsewhere.
• It has google adverts plastered over it in prominent places. *Furthermore, it seems to be run by phamaceuticalword.com/ pharmapromo.com.

Spam?

Increased Cholesterol & Paroxetine

I'm hesitant to edit the article directly as I've no medical background, but I've discovered two studies that indicate Paroxetine can lead to increased cholesterol levels in otherwise healthy patients. This seems an important enough issue to be mentioned here.

[[1]] "Blood samples were collected at baseline, after 8 weeks of paroxetine administration, and post-discontinuation in 18 healthy male volunteers. RESULTS: In the 16 of 18 patients whose plasma levels of paroxetine indicated an unequivocal compliance to treatment, paroxetine administration induced an 11.5% increase in low-density lipoprotein cholesterol (LDL-C), which normalized after paroxetine discontinuation."

[[2]] "We examined serum cholesterol and plasma catecholamine levels in PD before and after paroxetine treatment. The serum cholesterol and plasma catecholamine levels were not different between the PD patients and control subjects before the treatment. However, the levels of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were significantly increased in the 28 PD patients after 3 months of paroxetine treatment, whereas the body mass index and plasma catecholamine levels were unchanged."

Citation reference

"Paroxetine is a phenylpiperidine derivative which is chemically unrelated to the tricyclic or tetracyclic antidepressants. In receptor binding studies, paroxetine did not exhibit significant affinity for the adrenergic (α1, α2, β), dopaminergic, serotonergic (5HT1, 5HT2), or histamine receptors of rat brain membrane. A weak affinity for the muscarinic acetylcholine and noradrenaline receptors was evident. The predominant metabolites of paroxetine are essentially inactive as 5-HT reuptake inhibitors." Care to provide citation/reference pls? Uniearth 23:00, 14 November 2006 (UTC)

Rewrite

This page needs a serious rewrite. Not only does it contain numerous subtle flaws and biased statements, it is generally misleading and strongly worded to dissuade readers against paroxetine's usage. A more thorough, analytical model should be implemented, to better inform of paroxetine's use. I think part of the problem is that there have been too many people posting their own views on this page, and wording them to resemble facts. Wikipedia is not a forum, it's an encyclopedia. And as such, every article needs to be totally unbiased and devoid from any subjective views. --Prisonnet 14:41, 1 November 2006 (UTC)

"Both of the studies concluded that Paxil is significantly more effective than the placebo control group." where is this referenced from? the recent documentary on bbc2 stated that it was no more effective than a placebo, both cannot be right.

The BBC2 Panorama documentary, The Secrets of Seroxat, was correct. Overall, it is no better than placebo. Only studies showing positive benefit, however slight, were submitted to the FDA. The trials where paroxetine fared worse (or far worse) than placebo were not revealed and were kept sealed by GSK.

It has to be significantly more effective than placebo, or it would not be approved by the FDA and similar drug-monitoring bodies. Sometimes individual studies do not adequately demonstrate or disprove efficacy, which is why repeated studies are done with the largest possible groups. --72.192.118.171 18:06, 8 March 2007 (UTC)

I use Paroxetine for symptomatic relief for PTSD following witnessing a friend's death on the road. The notion that it works only as a placebo is completely ludicrous. It's been a lifesaver, and, in my case had an immediate and physically notable effect on my nervous system, which levelled out over a period of weeks. Not that I believe it should be used without due care and adequate supervision... I was cranky for the first month, to put it mildly. From speaking with others taking the drug, the concensus is that it creates in the user an increased propensity towards generally transgressive behaviour, which includes suicide. I do feel that, overall, a little more balance is required in the article, as there are certainly good and bad things about the use of paroxetine, rather than nothing at all as has been suggested.For what it's worth I speak as someone who lost a family friend to an overdose (of unknown motive) whilst taking the drug, and began to self-harm after going on it myself. Beg your pardon my subjectivity, but I feel it's relevant. 82.45.245.131 (talk) 00:01, 3 October 2008.

Any Thoughts?

I realise this isn't a discussion board, but my case seems unusual, particularly as a known side effect of the drug is a reduced sex drive. Anyway, my doctor prescribed me Paxtine (20mg per day paroxetine) as a solution to impotence. I'm just beginning it now - I have a high sex drive/libido naturally, and my problem is most likely anxiety related which this drug is supposed to be able to cure. Just thought it was weird/unusual case. Such a use of the drug certainly isn't mentioned in the article. Any thoughts? (unsigned)

I've also been on Paroxetine, 20mg per day for depression, and I've found my sex drive has increased alot, rather than decreased.. I think that the decreased sex drive can be a side effect of withdrawl, rather than the drug itself. (unsigned)

In the first case, your doctor may feel that a reduced sex drive might actually decrease your anxiety and therefore address the cause of your impotence. In the second case - decreased sex drive can also be a symptom a depression, in which case, getting rid of the depression might improve your response, to the point where the drug's own libido-squashing effect is eclipsed. (I'm not a doctor, but I'm well familiar with Paxil.) 72.70.26.80 11:30, 17 March 2007 (UTC)

Biased

This page is terribly biased against paxil.

The side-effects, possibilities of suicidal ideation, and withdrawl symptoms (although worse with paxil) are portrayed on this page as only being consequences of taking paxil, whereas all effects of paxil can occur with any ssri.

In addition, these effects of SSRIs are known to be more individual than with most other medications, with some patients receiving absolutely no side effects, and others having numerous ones. This page does not reflect that, but rather implies that all the side effects with occur with everyone taking it.--Prisonnet 20:39, 29 June 2006 (UTC)

- I have taken Prozac for 6 months and never felt any discontinuation effect. I have been on Paxil for only 4 months and the withdrawal is killing me. I feel intense electric shocks every 5 secs that are sometimes intense enough to make me lose balance or have Parkinson's disease like body tremors. Paxil withdrawal is HELL, no bias there.

Editing by GSK?

A suspicious number of the editors of this article have only ever made edits to this article, all of which are edits to make the article more favorable to GSK.

I think you're right. I had made a few written observations concerning some of the outright LIES (concerning efficacy and "trial" results) presented in this article and they were immediately deleted. And I mean within a few minutes. Makes one wonder if GSK is constantly monitoring this wiki page as a form of damage control. Sections of the page are an blatent advertisement by GSK to promote Paxil. This is an encyclopedia article about the generic chemical paroxetine. Not an advertising platform for GSK to persuade people to "Eat More Paxil."

Request that article be locked? This is a real concern for some of us that want to be sure we are reading the real Wikipedia article and not some GSK propaganda...24.251.84.221 12:41, 19 October 2007 (UTC)

Yes, this article DOES need to be locked. On May 12, 2006, the FDA itself finally released a warning that Paxil makes depressed ADULTS suicidal. Period. Said paroxetine-medicated people are 6.4 times MORE LIKELY to have suicidal thoughts (ideation) as compared to placebo. This is now (and always has been) fact. Quite a contrast to the "remarkable efficacy" touted in this article. Well, of course... That "information" comes straight from GSK's fraudulent "trials" As well as straight from GSK's ever-so-twisted sense of morality combined with its insatiable appetite for profit. LOCK IT! And let's get these facts straight. We need truth and facts here. Not Pharma propaganda like mentioned above.

Brain zaps

I'm surpised nobody's mentioned "brain zaps". The "zaps" are most likely some sort of seizure associated with Paxil withdrawl. They feel like electric shocks inside your head. Many people report them. A simliar condition may result from consumption of MDMA.

True, but its better way to drug yourself than MDMA i think so...

- Paxil withdrawal is real torture. I couldt believe no mentions of the zaps either , thats why i added it. Its not merely "zaps" it really feels like an intense electric shock, intense enough to litteraly throw you off balance or make you have parkinsons disease like body tremors. It is utterly irresponsible for a drug company to market such a drug without telling patients UPFRONT what they are getting into. The withdrawal is 10x more unpleasant than the reasons why i started taking this medicine. Being shy and feeling ackward in social gatherings will feel like a blessing from god once i am trough with the withdrawal... those drugs makers are terrorists, they are torturing me and they actually demanded money for doing so. Incredible... Paxil is the worst drug i have EVER taken, legal or illegal.

The "zaps" are mild and very infrequent. It reminds me of the sensation when you are dreaming you fell out of bed and get startled... it is more like a startle than an electric shock.

Withdrawal

I know someone who was on Paxil. His doctor switched him over to Effexor, and didn't have him taper off use of Paxil. He didn't notice any withdrawal after he stopped using Paxil.

JesseG 03:32, 2 Jun 2004 (UTC)

Personally, I have been on 150mg a day (Slow Release form) for nearly a year. Didnt notice any real withdrawal after a rather quick stop.

Really? I can't go an 25 or so hours without feeling withdrawl symptoms. The-dissonance-reports 03:56, 12 December 2005 (UTC)

not everyone experiences withdrawal. as stated in the article, about 1/3 of users experience withdrawal, so it's not odd that you might personally know someone who stopped with no problem. but a full third of users experiencing from mild to severe withdrawal is a serious problem, especially in a widely prescribed drug.

I was on a low 25-50 dose for around 6-7 months (I think) and I experienced withdrawal. Shocks, anxiety, strange sounds..etc

I was under Paxil during eight months (20 mg per day), and I ended the treatment cold turkey, so I experienced some withdrawal symptoms like the electric shoks, sweating and headache. This caused me to take the medicine for one more month, but this time I ended the treatment gradually and I experienced no withdrawal symptoms at all. So I think if people inform themselves more about the drug and how they should quit it, all this problem about withdrawal would end.

I have been on Paxil for years and the only reason I'm still on it now is because of "The Zaps". I've tried a few times to just deal with them, but it's really difficult.

I have experienced Paxil withdrawals as well including dizziness, a severe feeling of weakness, and terrible brain "zaps". I'm still cutting down and even just a few mg reduction results in the onset of these symptoms within 36 hours. I was on 20-40 mg for five years and I am now taking 7.5 mg. They initially adminstered the drug to me at age thirteen. I believe more should be said about its use in children and the possiblility of severe withdrawal. I have spoken to people who have experienced permanent gastrointestinal problems because of the drug.

D. Scott 2006-12-13

I've been taking Paxil CR for a while now. I have had the unable to reach orgasm issues as well as the loss of sex drive. The loss of sex drive seems to have gone away, and I find that the frequency that you have intercourse seems to inflate or deflate the affects of the unable to orgasm. The more frequent, the longer it took to reach orgasm, if at all. It was almost like a numbing of the nerves in the genitals, so to speak.

That's why GlaxoSmithKline is now trying to promote Paxil as a "treatment" for premature ejaculation. ANYTHING to squeeze another sacred dollar out of their evil concoction. Take a serious and no doubt troubling side effect and spin it once again to seem like a benefit of some kind (think Viagra's "four-hour erection" tactic). Sure, you may last longer in bed. If that is your goal. However, will that man REALLY know what he'll be getting himself into? Having to endure the myriad of other side effects as well as the Hellish withrawals? Most likely not. But, hey, GSK stock will rise. And that's always been the main objective, right?

As for withdrawls, I never got the brain zaps, but I do get dizziness and a feeling of disorientation if I forget to take it for over 24 hours, and I get a lesser feeling when I'm trying to cut down the dosage (I went from 50mg of the CR to 25, now back to 50mg). I'm taking it for OCD primarily, and anxiety as a secondary (brought on by the OCD).

Studies

Whever one says "recent studies have shown," it would be best to give citations, especially when the results are controversial, as any new results concerning a widely-used drug like Paroxetine would be.

I agree, I took the UK form of seroxat for a year and coming off was hell , I cannot comprehend how they can class it as non-addictive, surely when you take another pill to make the side effects go away and therefore chill you out , it is a simple fix, or is it me.

Simply put the drug has a high dependency on depression and when the user stops , unless supported by another SSRI it will cause all of the above and more in my experience.

I am a current user and i have started going trew the effects of withdraw. i lost my medical and could not afford my medication. I was feeling so bad i did'nt even leave my room. my family ended up borrowing the money. because at the point of time i was even in tears and could'nt stand because i would get dizzt and fall. what i am saying is i know there are withdraws and i will go trew them again because my refills are out and i can not get to a doctor until 26 september. so for anyone out there beaware because i was not informed of the side effects or the withdraw issues that the medicen had. —Preceding unsigned comment added by 71.114.169.221 (talk) 00:51, 4 September 2008 (UTC)

Suicide risks

I was under the impression that the reason the medicine appeared to make people prone to suicide was that the ideation was already there, but they didn't have the energy before to carry out their plans. The medicine gave them that energy to attempt or complete suicide.

JesseG 02:59, Nov 20, 2004 (UTC)

Not true IMHO. My wife was given Seroxat for Post-natal depression. During this period she gained significant body mass (not through eating) and attempted suicide twice. There is no family history or pathological history of this from her.

I can only assume that the drug altered her seratonin levels in a negative fashion and affected thyroid function. Three consultants have concluded that this was not caused by any stress/trauma/post-operative conditions relating to the birth.

Our intention is to sue GSK (who ironically I worked for a few years back) but we are still battling the immediate problems caused by it.

Sorry - i'm not a *registered* wikipedia user.

A new book was published in 2008 called Side Effects, by Alison Bass, (she's a former reporter with the Boston Globe). Her work uncovering certain bits of information should absolutely be looked at. I'm halfway through it, and another drug that's heavily covered in the book is Prozac.

GravityIsForSuckers (talk) 02:00, 13 December 2008 (UTC)

I will respond here to mwalla's links on suicidality ([3] and [4]). Both are to studies of patients diagnosed with clinical depression, which mwalla notes is already a risk factor for suicide. Paroxetine is widely prescribed for other disorders, for example generalized anxiety and social anxiety disorders, so the studies do not provide a representative sample of paroxetine customers. Also, as LiteratureGeek described, even if the net effect is fewer deaths in a given population, the drug might be preventing some deaths but causing others. The FDA-mandated boxed warning is based on the fact that paroxetine can definitely cause suicidal ideation and may thus increase the risk of actual suicide. Aggregate sums from non-representative populations do not change the characteristics of the drug itself.TVC 15 (talk) 08:36, 26 January 2009 (UTC)

Link to serotonergic

I removed the link to serotonergic from the pharmacology section which is currently (probably inappropriately) a redirect to Noradrenergic and specific serotonergic antidepressant. --Overand 00:01, 26 Apr 2005 (UTC)

I've seen it cause a successful suicide. Pharmaceuticals are so synthetic... do YOU know what's in them?

All antidepressants have the potential to incite suicidal ideation. The fact is, they've saved far more lives than they've cost. --Prisonnet 18:08, 8 March 2007 (UTC)

Side effects

In my case, one of the side effects was weight gain. From a slightly underweight 61kg (at 1.80m) to 70kg. I didn't gain any weight at all in the prior years (took it at age 20-21). Also excessive transpiration seems quite common (at least that's what my psychiatrist told me). This should of course be regarded as purely anecdotal. Personal accounts have reported that this drug has caused blackouts followed by extreme rage.

I believe I am not sleeping well because of this drug. My sleeping patterns have been dramatically effected after starting this medicine. Though I feel better in the day, I'm not sleeping well.

I've had the same issues. I took this medicine when I was 16-18, no side effects until after I got upped to 60 mg. Within two months of upping the dosage, I had gone from 105 pounds to 158 pounds. I quit taking Paxil because the weight gain caused more anxiety and depression than I'd had in the first place, and after quitting the drug, I lost 55 pounds in a matter of three months (with no change in diet or exercise). I'm 20 now, and I've recently gone back on Paxil for panic disorder. Going back on this medicine is so difficult the first few weeks. I can't sleep more than 2 hours at a time, and I'm never hungry anymore, yet I feel energetic. It's worth it to me personally though, because I'd rather have severe insomnia than have panic attacks any time I leave my home. I'd tried psychotherapy, changes in diet, Xanax, and many other things, and Paxil has been the only thing that made any real difference.

NPOV - let's clean up

This article is poorly written and POV. Rather than primarily informing, it emphasizes controversies without explicitly grounding discussion on credible publied sources and is overly influenced by personal anecdote. A recent retrospective study suggests increased suicide risk results in adults from taking paroxetine.[5] This may well stimulate a flurry of low-quality edits here just when readers will be consulting this article for an "encyclopedic" perspective. Let's clean up our act quickly and have a respectable presentation readied for the onslaught. Myron 06:30, 23 August 2005 (UTC)

The discussion on addiction rests on misapplication of the term and should be eliminated as being misleading. The Wikipedia article provides the currently accepted definition: "uncontrolled, compulsive use despite harm". Paroxetine is not associated with craving and does not produce pleasure or dramatic short-term relief of pain or anxiety. Physical tolerance occurs to certain adverse effects but not to the desired effect (i.e., there is no tachyphylaxis) — the "poop-out" phenomenon is not classified as tolerance — so that another criterion for addiction is not satisfied. Thus addiction is not an issue with paroxetine and does not even deserve mention (any more than one would discuss addiction with regard to aspirin). While physical withdrawal reactions are a major concern with paroxetine, more so than with other serotonin reuptake inhibitor drugs, mention of this belongs under the heading of adverse effects. Myron 07:32, 24 August 2005 (UTC)

Personal accounts have reported that this drug has caused blackouts followed by extreme rage.

This article is not POV. If your concern is that the article is repeating anecdotal information, it warns the reader of that. However, Paxil withdrawal syndrome is not speculation based on a few scattered user reports. It is documented in at least the following journal articles:

Independent Reports: 1993

Is there a serotonergic withdrawal syndrome? Biol Psychiatry 1993;33:851-2. Mallya, White, Gunderson.

Paroxetine (Paxil) "We have received 78 reports of symptoms occurring on withdrawal of paroxetine, including dizziness, sweating, nausea, insomnia, tremor and confusion. Such reactions have been reported more often with paroxetine than with other SSRIs. Reactions tended to start 1-4 days after stopping paroxetine and in several patients resolved on re-instating treatment. Paroxetine should not normally be discontinued abruptly". 1993 Committee on Safety of Medicines & Medicines Control Agency (Great Britain)

1995

Withdrawal syndromes after paroxetine and seatrain discontinuation. J Clin Psychopharmacol. 1995 Oct;15(5):374-5 Fava GA, Grandi S.

A possible paroxetine withdrawal syndrome. Am J Psychiatry. 1995 Apr;152(4):645-6. Phillips.

Paroxetine withdrawal syndrome. Am J Psychiatry. 1995 Jan;152(1):149-50 Pyke.

Potential withdrawal syndrome associated with SSRI discontinuation. Ann Pharmacother. 1995;29:1284-1285. Lazowick, Levin.

1996

More cases of paroxetine withdrawal syndrome. Br J Psychiatry. 1996 Sep;169(3):384. Pacheco, Malo, Aragues, Etxebeste.

Antidepressant withdrawal syndrome. CNS Drugs. 1996;5:278-292. Lejoyeux, Adès, Mourad, Solomon, Dilsaver.

1997

Paroxetine withdrawal syndrome in a neonate. Br J Psychiatry. 1997 Oct;171:391-2 Dahl, Olhager, Ahlner.

Paroxetine discontinuation syndrome in association with sertindole therapy. Br J Psychiatry. 1997 Apr;170:389 Walker-Kinnear, McNaughton.

Antidepressant withdrawal syndrome. Br J Psychiatry. 1997 Mar;170:288 Young, Currie, Ashton.

Newer antidepressants and the discontinuation syndrome. J Clin Psychiatry. 1997;58(suppl 7):17-22. Haddad

Possible biological mechanisms of the serotonin reuptake inhibitor discontinuation syndrome. J Clin Psychiatry. 1997;58(suppl 7):23-27. Schatzberg, Haddad, Kaplan, Lejoyeux, Rosenbaum, Young, et al.

SSRI Withdrawal Syndrome 1997, American Society of Consultant Pharmacists, Inc. Skaehill, Welch

1998

Treatment of disequilibrium and nausea in the SRI discontinuation syndrome. J Clin Psychiatry. 1998 Aug;59(8):431-2 Schechter.

Withdrawal syndrome associated with abrupt discontinuation of SSRIs. J Am Pharm Assoc (Wash). 1998 Jul-Aug;38(4):500-1 Wincor.

Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial. Biol Psychiatry. 1998 Jul 15;44(2):77-87 Rosenbaum, Fava, Hoog, Ascroft, Krebs.

Withdrawal syndrome caused by selective serotonin reuptake inhibitors. Schweiz Rundsch Med Prax. 1998;87:345-348 Bryois, Rubin, Zbinden, Baumann.

Selective serotonin reuptake inhibitor discontinuation syndrome: putative mechanisms and prevention strategies. Can J Psychiatry. 1998 Jun;43(5):523-4. Rojas-Fernandez, Gordon.

1999

Selective serotonin reuptake inhibitor discontinuation syndrome: putative mechanisms and prevention strategies. Can J Psychiatry. 1999 Feb;44(1):95-6. Benazzi.

2000

Withdrawal syndrome after the use of serotonin reuptake inhibitors. Tidsskr Nor Laegeforen. 2000 Mar 20;120(8):913-4. Fagan.

Serotonin discontinuation syndrome: does it really exist? W V Med J. 2000 Mar-Apr;96(2):405-7. Nuss, Kincaid.

Paroxetine withdrawal syndrome. Ann Med Interne (Paris). 2000 Apr;151 Suppl A:A52-3. Belloeuf, Le Jeunne, Hugues.

Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria. J Psychiatry Neurosci. 2000 May;25(3):255-61. Black, Shea, Dursun, Kutcher.

It is serious enough of a concern that it merits more than a mere notation as a "side effect."

I removed the section about "lasting sexual dysfunction." I have never seen a credible source showing permanent, adverse effects of SSRIs. Please, leave the unwarranted claims off of Wikipedia and stick to the science. Furthermore, since when do Paxil withdrawal symptoms last from "months to years?" I believe it's accepted that SSRI Discontinuation Syndrome resolves, at most, after a few weeks without restarting medication. This article certainly needs a clean-up--the author obviously has a strong bias against SSRIs, as also evidenced by condescending language such as, "As soon as you pop a pill..." The "addictive potential" section is especially poorly written. Perhaps the work of Scientologists playing around on Wikipedia? --AJ

Unfortunately, AJ, the "science" must be analyzed for credibility as well. There are few studies showing adverse effects of paroxetine because such studies are not in line with the interests of GlaxoSmithKline. Thus, we need to become competent consumers of research and selectively analyze each research study to see what Pharma connections its authors hold. Additionally, I think the "scientology" comment is out of line; simply because someone does not believe the hype about pharmaceuticals does not make them a scientologist. Your comment is akin to saying that if someone likes fried chicken, they must be black. It's faulty logic like this that leads the world into trouble. -Alex

AJ, you say: "I believe it's accepted that SSRI Discontinuation Syndrome resolves, at most, after a few weeks without restarting medication." I'm sorry, but this is incorrect. Perhaps the reason for the confusion is that persisting adverse effects from previous SSRI use are not the same thing as what is referred to as "discontinuation syndrome". That syndrome is a direct consequence of rapid neurological change from stopping the medication, and yes the obvious symptoms (such as "zaps") generally resolve within a month. Longer-term issues are a consequence of alterations made to the brain during chronic SSRI use (and, especially in the case of paroxetine, the endocrine system), rather than a "withdrawal syndrome" as such. This condition is closer to a post-acute withdrawal syndrome, and is characterised by a non-linear recovery - good "windows" and relapses - and yes, it CAN include sexual dysfunction. It comes with a host of physical symptoms, so has nothing to do with relapse into the original condition. The reason it is underreported is that most long-term SSRI users, faced with post-withdrawal issues, end up back on an SSRI or another psychotropic drug, usually at a doctor's suggestion. As time goes on, and more and more long term SSRI users attempt to cease treatment altogether (either because of poop-out, spiralling side-effects or actual recovery from the initial illness), this condition becomes more common. In 1995, you would have been right to query it, as it was indeed very rare. In 2007, you are somewhat behind the times if you cast doubt on long-term damage from the chronic use of these medications. I do agree that much of the phrasing in this article is very poor and unscientific, but that's a separate issue. And the "scientologist" remark is extraordinarily ignorant. MrBronson 22:02, 22 March 2007 (UTC)

Although things are now more correctly cited, this article is still heavily biased against Paroxetine's use. DirectorStratton 04:30, 1 March 2006 (UTC)

I can't help but wonder how many of the charges of bias are written by GSK or its sockpuppets.

Paroxetine experience over 12 years of therapy

Paroxetine has allowed me to feel "normal" for the first time in my life. I began taking paroxetine 12 years ago. I started taking 10mg once every day. I now take 25mg CR everyday.

After taking paroxetine for approxinmately 4 years, I tried to taper down and stop taking it. For me, this caused the "zaps" within days. I also had auditory hallucinations, vertigo to the point of not being able to drive or even walk at times and complete loss of libido. Fromj a psychological side, the acute mood swings returned almost immediately as did the depression.

I tapered down over the course of two months with no adjunctive chemical therapy. I continued to see my Psychologist. After four more months of what I experienced as a worsening of my physical and mental conditions and despite continued psychotherapy, I restarted paroxetine with 20mg every day.

Except for the increase in somnolence and returned ejaculatory disability, I returned to "normal". The somnolence passed in about six to eight months. Viagra allowed me to maintain an erection for long enough to have a reasonably normal sex life.

I did try to stop paroxetine therapy once more, about four years ago. Not by choice, but because I lost my medical insurance. At the time, before the patent expired and generic paroxetine was available, it would have cost me over three hundred dollars a month for the medication.

Again, I tapered down over a course of 3 months. Within weeks of decreasing the daily intake, I was acutely unstable physically, mentally and emotionally. This six months was much worse than the earlier attempt and by far worse than I'd been before starting paroxetine therapy. I did continued therapy sessions with a psychologist. For my own sake and that of my family, I began taking paroxetine again.

I can only relate the facts of my own experience. In discussing SSRI treatment with other people that I know who take SSRI's, my experience is not unique.

I will continue to take paroxetine now for two reasons. One, because this particular medication seems to allow my body and brain to act and react in the real world in a more "normal" fashion. Two) because the side effects of not taking it are so debilitating.

To say that a drug makes one behave or think "normally" is close to a contradiction-in-terms in my opinion. It is simply impossible for one to judge the nature of "normal" personal existence as one lacks experience of another individual's subjectivity. Surely you mean that you are placed on a plateau by the drug - it is this "high" which is the reason for your satisfaction and not any imagined normalisation effect. The drug achieves its purpose by reducing the user's consciousness of the moral value of his own actions; he is taken on a rollercoaster ride where his inhibitions are suspended which approaches zombification of the subject. The reason the user persists with the drug is that it makes him less aware of his own identity and ego as does any drug illicit or otherwise. By reducing "anxiety" - which is, after all, a mundane affection - it reduces pain. Of course, the user (and the drug company for that) will try to cover his guilt for enjoying the psychological dissociation by describing the effect as "normalisation"; a conclusion which is clearly absurd. These are a few reflections on the drug from a Freudian perspective. --Nicander 07:34, 13 March 2006 (UTC)

Okay...I agree that Paxil apparently seems to have a big problem with withdrawal effects. However, there are also many ways to get around that, such as switching to Prozac and weaning off of that (whose SSRI discontinuation syndromes are almost non-existent)--there's no reason to simply stay on Paxil forever because of the withdrawal effects. However, it's also possible that the feelings of instability came from returning depressive symptoms (which is likely, given that many mildly depressed people have no trouble weaning off). Your argument about if a person can be more "normal" while taking a medication is a decade-old moral debate that simply doesn't have a clear answer. Just some thoughts/advice, but of course, I'm not a psychiatrist. --AJ

seroxat

Dont EVER take this drug, my father took 10mg of seroxat for the first time and after 12 hours he tried to kill himself by hanging!!!!!!!!!!!!!!! When my mother found him, she unhooked him from the rope, he was alive, but acted like he was in trance or something (he didnt respond, his eyes were going from left to right). If someone from your family got it prescribed, steal it and burn it, or make sure you watch him day and night.

So, this page is terribly biased against Paxil (Seroxat). GOOD!

I spent nearly eight years in a haze of exhaustion courtesy of this foul drug. The only thing worse than the side effects was trying to withdraw.

In the end I withdrew with the aid of Citalopram but not before my marriage was in tatters and my life nearly ruined.

It's interesting that my G.P. now refuses to prescribe it on the grounds of the side effects and withdrawal symptoms.

There are other, far better anti-depressants on the market. If your doctor does prescribe this for you then please take my advice, rip up the script and find yourself a more enlightened doctor.

I have no axe to grind with GSK. I would like to say this is purely my experience but everyone I know who was prescribed this drug (during the late'90's) experienced a measure of the same side effects and withdrawal problems.

Seroxat? Just don't go there.........

Compliance:

"Paroxetine users should not discontinue and resume treatment with more than a few days' gap between dosings, as paroxetine decreases in effectiveness if it is stopped for a significant amount of time, and then resumed."

I would like a reference for this. Of course effectiveness decreases if you do not take the medication at all. But does it have any long term repercussions?

Warnings

Everyone who is adding ridiculous warnings about 'birth defects' and such need to stop immediately. Adding this section, besides being biased, is not needed. Paroxetine is in pregnancy category D, so of course it's going to cause birth defects. Just like ibuprofin, aspirin, and warfarin can cause birth defects. The warning already exists in its pregnancy class, it is not appropriate nor necessary to include this section in any medical article of an already pregnancy-scheduled substance. The same applies for suicide warnings. Besides being already stated on the page, all antidepressants already carry this warning.--Prisonnet 18:29, 24 August 2006 (UTC)

Negative side effects

It has not been mentioned that seroxrat may lead to violent or self harming behaviour that could even be described as physchotic, if you have any worries then contact your GP or primary health care provider, REMEMBER! there is no obligation for you to take an SSRI if you feel that it may not be in your best intrests, it is better to go through a week of cold turkey from this drug than to find yourself under arrest for assault or murder (written by 82.7.91.80, moved by Dirk Beetstra ^{T C} 06:29, 29 August 2006 (UTC))

I have experienced increased hostility (including 'blackouts')on Seroxat (paroxetine). It me took almost a year to taper off the drug gradually, using the liquid formulation, and severe moodswings persisted for at least four months after that. Most of the evidence linking paroxetine to increased hostility is anecdotal; my GP (who has an active interest in mood disorders) stated that "of course it's well-known that biopolar individuals can be very unpleasant on Seroxat"--if only I had known... No scientific reference, but a lot of personal comments can be found on this website: http://www.mcmanweb.com/article-219.htm Note that many patients report excessive and uncharacteristic alcohol cravings on this medication. [Denni Schnapp--not a registered wikipedian]

Molecular Weight

Although Molecular formula for Paroxetine is given, the informed molecular weigh (374.8) corresponds to Paroxetine Hydrochloride hemihydrate: C19H20FNO3.HCl. 1/2 H2O. Paroxetine (alone) should be 329.37

Chemistry Equation To Withdrawal Adverse Experiences (removed***)

Hypothesis suggests neuron/receptor damage a more likely cause for suicide than the simple pre-existing suicidal ideation claim and deserves study into consumption and elimination of Fluorine by exact weights of each.

A durable *Teflon like molecule develops from the fluorine-carbon bond in Paroxetine. Certain atoms should not be in the nervous system beyond the blood-brain barrier because they would cause disruption of delicate meninges and receptor damage upon chemical breakdown and synthesis.

The presence of halogens which need only one valence electron to fill their outer electron shells causes an incorrect synthesis, leaving non-transportable molecules to cause what must occur by laws of atomic, chemical and physical properties such as long-term or permanent receptor blocking or burning of delicate meninges by molecular Fluorine.

Not all SSRI compounds contain Fluorine. Prozac has three atoms in contrast to Paxil's one. Fluoxetine is less profitable to Paroxetine, damaging the buyer more quickly. Only natural molecules of carbon hydrogen nitrogen and oxygen are acceptable to the nervous system for normal function**.

Low levels of Seratonin proportionally decrease normal neuronal activity and chemistry in the first instance where an SSRI only magnifies problems.

Low levels of Seratonin have been associated with several disorders, notably depression, migraine, bipolar disorder and anxiety.

Dare we trust what is currently approved? Give some thought to that question before answering. Anyone just reading the facts might become suicidal let alone someone who has been damaged by the very system which causes such extreme societal pressures. Inappropriate trials conducted for cost and gain considerations without regard for the few is or should be well known.

When you fly in first class, it's easy to forget the dots[6]

• Teflon: A carbon-fluorine chain.

• • That no similar and transportable, halogen containing molecules are found in normal and healthy individuals who have never taken such SSRI drugs and the result of the presence of molecular Fluorine supports an acceptable theory.

• • • Citing data from the World Health Organization, "Paxil has the highest incidence rate of withdrawal adverse experiences of any antidepressant drug in the world". Is this not a factual quote?

Given that the recommendation for discontinuation syndrome is factual, I am appalled. Doesn't anyone think for their own self, blindly following such arbitrarily achieved guidelines of a corrupt system. Phenothiazine-derivative drugs are from DuPont introducing Phenothiazine as an insecticide in 1935.

Isn't Flourine used to help it cross the blood brain barrier, why don't they just add an acetyl group instead?

Codeine and Paroxetine?

I know this isn't really a discussion board, but i've been put on paroxetine in the past few days. Sometimes I get bad headaches, I take an OTC tablet (2) known as nurofen plus (200mb ibuprofen + 12.8mg codeine) which helps a lot. I've heard that Paroxetine actually stops the effects of codeine. Does anyone know much about this, and if it's true, are there any equally effective alternatives for pain relief? Timeshift 12:56, 2 November 2006 (UTC)

Timeshift, I took codeine for a cough while on paroxetine; the codeine didn't work. It actually had a bit of a backwards effect -- it made me hyper. Who knows, though. The folks at www.paxilprogress.org are helpful; perhaps ask them? -- Alex

I am appaled by the quality of this entry

The statement: "In common with previous editions, the programme presented an entirely one-sided picture of events, and could be argued was little more than a television broadcast on behalf of Baum Hedlund, the lawyers acting against GSK" is completely out of place. The tone used is unprofessional and unfortunate. It raises the question if the writer is taking parts on this issue. As stated before, gsk is being sued for millions of dollars over this drug; it is in inappropriate for wikipedia to profess biased opinions about this matter, the drug, the company, or other people involved in this dispute.

Pharmaceutical Assassination

I will attempt to get USA Today's permission to reprint here.

The dark side of psychiatric drugs - The United States of Violence: A Special Section - Cover Story USA Today (Society for the Advancement of Education), May, 1994 by Tanya Bibeau [7]

Alphaquad 05:18, 7 March 2007 (UTC)

Unacceptable sources to be deleted

Mewstarget.com website, seroxat secrets website, Paxil protest website, Hugh James solicitors website are not acceptable sources according to the Wikipedia guidelines, and I am deleting them.

Wikipedia:Reliable sources guideline (WP:RS) states: "Articles should rely on reliable, third-party published sources with a reputation for fact-checking and accuracy. Sources should be appropriate to the claims made."

Wikipedia:Self-published sources guideline (WP:SPS) states: "Anyone can create a website or pay to have a book published, then claim to be an expert in a certain field. For that reason, self-published books, personal websites, and blogs are largely not acceptable as sources."

Paul gene 13:10, 2 September 2007 (UTC)

I've added the bit about Robbie Williams back in as the report in the Sun does clearly mention Seroxat: "The singer finds it impossible to get to sleep until 4 or 5am due to insomnia and is on sleeping pills. He is hooked on the powerful and controversial anti-depressant Seroxat, which has been linked to suicidal tendencies in teenagers." Experimentalchimp 16:19, 8 September 2007 (UTC)

I've also put in some information on the UK lawsuit, which is similar to some of the sections you removed. It's rewritten and should conform to (WP:RS). The whole controversies section is probably in need of a rewrite as it's a bit of a mess at the moment, but hopefully having correctly sourced information there's a starting point. Experimentalchimp 23:30, 8 September 2007 (UTC)

The trade names are in alphabetical order.

I'm replying here to the comment below in order to save others' time, and changing the caption for the same reason. Me-pawel's original caption said to "get the names correct," in line with the comment below that Chile appears several times. Apparently, Me-pawel didn't notice that the list of trade names is alphabetical. The country of Chile appears repeatedly because paroxetine is sold under multiple trade names there. If there is a way to create a table in WP that can be sorted, then it would be helpful to have columns for 'trade name', 'country,' and 'region', but I haven't seen that anywhere. Meanwhile, I checked the listed trade names for Chile and confirmed all except Traviata, which I can neither confirm nor disprove.TVC 15 00:51, 13 September 2007 (UTC)

I don't know much about Paxil, but just by looking at this page I see several errors alone in the name section. For example:

Aroxat or Aroxat CR in Chile,

a little under that we have

Bectam in Chile,

More under that we have

Seretran in Chile

and...

Pamax in Chile,

and...

Traviata in Chile,

and finally

Posivyl in Chile,

So we have six different names for Chile alone. Adding to this we have "Cebrilin in Latin America" and the last time I checked Chile was in Latin America. Please help clean this up. (Me-pawel 05:43, 6 September 2007 (UTC))

comments by User:TVC 15 and User:Skinwalker

I've removed some of the GSK POV marketing puffery from the third sentence. (Previously, I had tried to balance it with court rulings and press reports of customer experience, but "Skinwalker" deleted that.) AJ's comments are undated, but clearly outdated. Also, AJ's comment above that there is no reason to continue taking paroxetine when switching to another SSRI will obviate withdrawal symptoms is misleading: SSRI's are prescription drugs so customers can't just buy a different one, they have to go back to a doctor for permission, and the doctors have been deceived by GSK marketing into believing that there are no withdrawal symptoms; GSK's prescribing information says to taper, not switch, so even the minority of doctors who have read of the "discontinuation symptoms" are given wrong information by GSK as to how to deal with it.TVC 15 17:13, 8 September 2007 (UTC)

"Skinwalker" struck again, deleting again the link to GSK's prescribing information on "discontinuation syndrome" and calling it "trial attorney puffery." I continue to try to assume good faith, but that is difficult when someone mis-characterizes a document mandated by government regulation as puffery, and keeps deleting it. "Skinwalker" also changed the sourced, factual statement that the drug causes withdrawal to a "he said/she said" as if it were unknowable or a difference of opinion. It is a proven fact; the BBC even reported a study showing the drug causes withdrawal symptoms in a majority of patients starting after as few as two weeks. (That would make it more "habit forming" than cocaine.) I will not speculate as to why "Skinwalker" keeps deleting factual statements unfavorable to GSK even when they are PUBLISHED BY GSK, but it would be interesting to investigate. GSK went to great lengths to tell the whole world initially that paroxetine was "not habit forming," but even after being forced to disclose the information on withdrawal syndrome, GSK disguises it ("discontinuation symptoms") and buries it, leading misinformed doctors to continue prescribing it because they have not read the updated prescribing information. If by some chance "Skinwalker" is working for GSK (which I do not assume), then (s)he may be exposing the company to charges of contempt.TVC 15 01:57, 10 September 2007 (UTC)

First off, please read the neutral point of view guidelines carefully, especially the section dealing with undue weight. The "he said, she said" approach is necessary for neutral writing. We give GSK's opinion, and then we give their opponent's position (or the other way around, I don't care which). We should not give undue deference to one point of view over another, regardless of your personal bias. Putting phrases like "serious discontinuation symptoms" in scare quotes in the lead paragraph is not very neutral. Finally, I'd like to state that I do not work for GSK, nor do I have any financial relationship with them. Your insinuation of "charges of contempt" border on a legal threat, which is quite frowned upon here. I'm willing to work with you on incorporating legitimate criticism into the article, but you need to assume good faith. Cheers, Skinwalker 16:17, 10 September 2007 (UTC)

Thanks for adding to the discussion - at last. If you read the top of this page, you will note that it says, "Please read this talk page and discuss substantial changes here before making them." You have made many changes to the article, but as far as I can tell you never provided any discussion until now. The discussion section includes several observations from different authors noting pro-GSK bias, so I am pleased that mine finally drew you in. As noted in my previous comments, I did assume good faith - despite the difficulty of that when you seem to favor a pro-GSK POV that even GSK has abandoned. With regard to conflicting opinions, however, your statement is simply incorrect. The withdrawal syndrome is an established scientific fact, admitted by GSK, backed by linkable studies in reliable sources, and concluded litigation. The only difference is whether to call it a "discontinuation syndrome" (GSK) or "withdrawal syndrome" (everyone else) so I used both ("he said, she said," you should be pleased). Your accusation of "personal bias" is therefore unwarranted and unappreciated. Your reference to legal threat is likewise misplaced. That policy states, "Do not make threats or claims of legal action against users or Wikipedia itself on Wikipedia." GSK is not, to my knowledge, a WP user, and no one has threatened WP itself. I am glad to read that you do not have any financial relationship with GSK, and I will continue to assume good faith, but please recognize proven facts and do not try to bury them.TVC 15 18:00, 10 September 2007 (UTC)

Hey, we all have a personal bias. I was simply noting that, not accusing you of it. My personal view of or bias toward these SSRIs is somewhat complicated. I was on venlafaxine, which also induces SSRI withdrawal, for several years. It was a huge help in terms of mood, but it was extremely unpleasant to miss a dose, and even more unpleasant to finally stop taking when it had outlived its usefulness. So I know personally the benefits and drawbacks of these medications, and I want to assure you that I am not trying to bury criticism of them.

What irks me about most, if not all, SSRI pages on wikipedia is the constant soapboxing and non-neutral commentary. People do not realize that blogs are not reliable sources, nor internet petitions. I'm not talking about you, specifically, most of these observations come from other SSRI pages I edit. The sourcing for this article, I think, is much better now - there are medical citations and good secondary sources from the BBC and so forth. My instinct is to use the phrase that the source uses, and if there is a discrepancy to neutrally note it. A sentence that begins something like "The BBC refers to seroxat's withdrawal symptoms, which GSK calls discontinuation syndrome..." is actually pretty damning, and uses neutral language to boot. At any rate, I suspect our differences may be more about specific wording that anything else. Can you make a proposal on how we can better cover the withdrawal/discontinuation issue? Cheers, Skinwalker 18:24, 10 September 2007 (UTC)

Here is what the article says currently:

Many psychoactive medications can cause withdrawal symptoms upon discontinuation from administration. Substantial evidence has shown that paroxetine has the highest incidence rate and severity of SSRI discontinuation syndrome of any medication of its class. That fact contrasts with GlaxoSmithKline's marketing of the drug, which initially emphasized that it was "not habit forming."[1],[2] (As of 2007, GlaxoSmithKline's prescribing information eschews the term "withdrawal" in favor of the phrases "serious discontinuation symptoms" and "discontinuation syndrome."[3]) Common paroxetine withdrawal symptoms include repeated electrical shock sensations of the brain and body (see "brain zaps"), vertigo and hot flashes.[16] For those experiencing extreme and unusual difficulty discontinuing paroxetine, it is recommended that an SSRI with a longer half-life, such as fluoxetine, be administered for approximately two weeks, then discontinued, to lessen symptoms.[17][18]

I think that covers it fairly well. BTW, the NY Times is currently running an interesting series on pain medication, especially morphine, which is cheap and effective but widely banned due to addiction concerns; the prohibition extends even to patients who are terminally ill (thus not worried about addiction) and writhing in pain.[8] I don't mean to suggest that the risk of withdrawal symptoms by itself makes paroxetine an evil product; what irks me most about it is GSK's initial marketing of the product as "not habit forming" when in fact it clearly is. BTW, I meant to correct my earlier statement: although GSK does now admit a risk of "discontinuation syndrome" in its prescribing information (having been forced to by regulators), the concluded litigation involves only minors; they are still litigating over adults. Also, I don't mean to suggest the FDA is perfect; they continue to say patients should taper off paroxetine, when in fact studies have shown that to be useless for the patient (useful only for the manufacturer which gets to sell more paroxetine even to people who have decided to quit); the WP article links to reliable sources that publish the better approach, which is to switch to an SSRI with a longer half-life and taper off that. (Generally speaking, the longer the half life, the easier it is to quit. venlafaxine has an even shorter half-life than paroxetine, and you would probably have had a much easier time quitting if you had simply switched to an SSRI with a longer half-life as noted in the article.) Unfortunately, drug makers won't tell you to switch to a competitor's product, and customers can't just go to the pharmacy and buy a different product, they have to pay a prescriber for another visit and try to persuade him/her that (a) the "not habit forming" drug is in fact habit forming, and (b) the solution is to follow the advice on WP not the FDA's advice. To the extent that we all have a personal bias, mine is against deceptive marketing and incorrect advice that customers are not allowed to ignore. WP offers a rare opportunity to make accurate information from reliable sources readily available, even if the reliable sources are medical journals that many doctors no longer take the time to read.TVC 15 06:39, 11 September 2007 (UTC)

I'm organizing (without substantively changing) the withdrawal section into a paragraph on symptoms and solutions and a paragraph on history. Also I've been looking for an article I read long ago that talked about the history of how the drug became so popular. (The WP article previously stated, without sources, GSK's POV that it's popular because it's so wonderful, but there is a contrary history backed by litigation: the drug became popular due to clever marketing and the difficulty of withdrawal.) As I recall, financial analysts covering GSK initially expected the drug to sell poorly because better drugs were already available and the short half-life would cause problems like withdrawal; then, GSK got the drug approved for previously rare diagnoses like "generalized anxiety disorder," and advertised those conditions on TV around the time of 9/11; nearly everyone was generally anxious and paroxetine was the only drug approved specifically for that purpose, so it became the most popular drug of its kind and the company's #1 seller; GP's and even nurses prescribed the "non-habit-forming" drug without hesitation, and later press coverage reported harrowing anecdotes of children and adults who couldn't stop taking the drug because of the previously undisclosed withdrawal syndrome. I think the WP article covers the later history fairly well now, but I would still like to find the article describing the financial analysts' forecasts and GSK's subsequent marketing the drug for previously rare diagnoses.TVC 15 19:59, 20 September 2007 (UTC)

Removed Robbie Williams quote

The following sentence about Robbie Williams is unacceptable: "On the 12th Of February 2007 singer Robbie Williams checked himself into rehab to kick his addiction to Seroxat."

First all, the original Sun's article says only that: "He is hooked on the powerful and controversial anti-depressant Seroxat". "Hooked" in this context is just a term of tabloid journalism, which, if considered impartially, means only that RW has been taking Seroxat. His supposed addiction is something the journalist is trying to imply, but takes care not to say directly. Furthermore, this quote does not say anything about RW checking into rehab with the expressed purpose of "kicking" that specific addiction.

Second, Wikipedia:Biographies of living persons recommends that, "Editors must take particular care adding biographical material about a living person to any Wikipedia page.'" and "Be very firm about the use of high quality references. Unsourced or poorly sourced contentious material – whether negative, positive, or just questionable – about living persons should be removed immediately and without discussion from Wikipedia." The quote from The Sun is clearly a contentious material, and The Sun is not a high quality reference.

Third, this material is irrelevant in a pharmacology article. Wikipedia:Biographies of living persons recommends that "Editors should avoid repeating gossip. Ask yourself whether the source is reliable; whether the material is being presented as true; and whether, even if true, it is relevant to an encyclopedia article about the subject." Paul gene 11:11, 24 September 2007 (UTC)

It is important to view Paroxetine side-effects in proportion to the benefits for the individual. In some cases, the side-effects might outweigh the benefits, in others the benefits might greatly outweigh any discomfort caused by the side effects.- I suffered all my life from depression probably caused by a combination of genetic causes and unresolved childhood trauma, leading to chaotic life style, alcohol abuse and various degrees of self-destruction. Paroxetine has helped me to quit using alcohol exessively, and improved my life quality immensly. I experience side effects such as dry mouth, decreased libido, and some irregularities of my sleep pattern, but I gladly accept these over the destructive power depression and the side effects of alcohol abuse. I believe that this drug, or maybe also other similar medications, can save lifes. I tried other medications, but Paroxetine proved most effective for me personally. I believe that depression can be a genetic disorder, because my father died of alcoholism, one of my brothers struggles with alcohol abuse issues, my sister is addicted to a strong narcotic and alcohol,and my other brother killed himself at the age of 28 as a result of heroin addiction. We all have one thing in common: depression. Each of us was/ is trying to find a remedy for the depression. I believe that if my brother, who killed himself in the 70's where research in this field wasn't advanced, had had the chance to be treated for depression prior to forming the heroin addiction this worst outcome of depression could have been avoided. I am thankful for Paroxetine. I discontinued Paroxetine when I found out that I was pregnant, and I don't recall any problems with the discontinuation. Under circumstances other than pregnancy it should be discontinued gradually, to me that is common sense, and would apply to any other drug or substance. Any sudden and radical change for the body might cause discomfort. Medications of such impact should never have to be discontinued involuntarily because of health insurance issues, which is a political problem that can now be countered by purchasing generic versions or purchase of the drug at less costly locations.--Mooresabine (talk) 12:23, 14 December 2008 (UTC)

Controversial?

In the opening description, the last sentence is "The prescription of this drug is controversial because of side effects such as suicidal ideation (thoughts of suicide) and withdrawal syndrome which have resulted in legal proceedings against the manufacturer."

This statement is too strongly worded. It is one of the most widely prescribed drugs, how can that be controversial. Soda pop has caffeine, but it is so common as not to be "controversial". Cigarettes are common and controversial because there is a causuational link between smoking and cancer. There is no causational link between paxil and suicide. Legal proceedings do not justify controversy, what drug or company does not face legal proceedings as a matter of ordinary life?

Wow, where to begin? The comment above is unsigned, but I would suggest reading the article sections on Controversy and especially the section on Withdrawal. At least in the US, a federal case is by definition a controversy (or else the complaint gets dismissed for failure to show a genuine case or controversy), and beyond that you have the reprimand from the industry trade group, the black box warning from the FDA, the reliably sourced history of suppressing information and misleading consumers, and so on. To call it controversial is putting it mildly. Stronger terms might include fraudulent, murderous, etc. As noted above, many of the current prescriptions result from the fact that the drug is habit forming, which the manufacturer had previously denied. Reliable newspapers have published individual patient stories reporting the harrowing withdrawal syndrome, including in children, forcing them to keep taking the drug despite its side effects. The BBC reported on a study that found paroxetine more addictive than cocaine. Also, heroin was originally marketed as a children's cough suppressant; it was popular for a while, but became increasingly controversial and was eventually banned (replaced by alcohol-based substitutes, which were also popular but have since become controversial too, at least in children). Popular and controversial are not antonyms. To the contrary, when a popular product is found to have flaws that had been concealed by the manufacturer, the degree of controversy can be directly proportional to the degree of popularity.TVC 15 (talk) 19:46, 9 January 2009 (UTC)

The "controversy" may have caused more suicides than it saved, as the blackbox warning prevented the appropriate administration of paxil which is believed to have lead to an increase in the suicide rate merely over fears of the "controversy". http://www.aacap.org/galleries/LegislativeAction/News_33_2007_0102.pdf

To compare withdrawl or dependency from paxil to that of cocaine is absurd.

Your use of "absurd" is surprising here: how can you understand the difference between two things without comparing them? Unless you have experienced both, how would you know which is worse? Even if you have experienced both, how would you know which is more likely to occur without reading the statistics? Read the study reported by the BBC, and let the evidence drive the conclusion. As for effects on the overall suicide rate, the same drug can have different effects in different people, so paroxetine may have prevented some suicides while causing others. The purpose of the black box warning is to alert prescribers, parents, and patients so they can look for suicidal ideation or behavior and thus save lives that would otherwise be put at risk by the drug. The definition of "controversy" requires at least two sides; GSK initially denied everything, but has now admitted the risks of withdrawal (which GSK calls "serious discontinuation symptoms") and suicide.TVC 15 (talk) 17:02, 12 January 2009 (UTC)

BTW, "Paxil" is a brand name, so if your goal is to help GSK, you might start by respecting their trademark. Generic versions now account for a majority of paroxetine prescriptions in the US; although generics are officially equivalent, they are not exactly the same.TVC 15 (talk) 17:21, 12 January 2009 (UTC)

Of course all things can be compared, but the only purpose served in comparing cocaine to "paxil" is to confuse and scare the general public. Cocaine is a banned substance while paxil is not. Cocaine is much more "controversial". Doctors prescribing paxil are likely to be concerned about suicide in the first place, I would not leave it up to the FDA to advise patients or parents in this situation, leave it to the doctor instead.

A search for "paxil" directs to this page. I do not work for GSK, why do you imply that? I and many others know it as Paxil and do not know what "paroxetine" or other chemical names.

What study reported by the BBC? I do not see the link and could not find it in a search, can you provide it? You ask me to respond to this "BBC" study but you did not respond to the Robert Gibbons study.

The article already links to at least two BBC reports. One reports a paroxetine addiction study, [9] and another finds the drug does not help teens but increases their suicide risk sixfold.[10]

In the UK (GSK's home country), the brand name for paroxetine is Seroxat. That may explain why you could not find the BBC reports searching for Paxil. If you want to find information, it helps to learn and use correct terms.

I did not imply that you work for GSK, in fact if you did you would probably be more careful of their trademarks.

The issue in this section is whether paroxetine is controversial. Obviously, it meets any serious definition (e.g., [11], controversy, [12]). Gibbons does not disprove the existence of a controversy. The drug may have some merits; it was approved and remains widely prescribed, as you say (although some number of those prescriptions reportedly result from addiction). However, the fact that some favor the drug while others oppose it is what makes it controversial.TVC 15 (talk) 18:04, 12 January 2009 (UTC)

BTW doctors in the US used to prescribe cocaine, then it became controversial and was later banned in this country. Likewise Vioxx used to be prescribed, then became controversial and was later withdrawn by Merck. GSK marketed Paxil on TV to practically everyone, not just those who are suicidal. Regardless of whom you personally would "leave it up to" to advise patients and parents (FDA, doctors, drug companies' TV ad agencies), the express goal of WP is to make knowledge available to everyone.TVC 15 (talk) 18:13, 12 January 2009 (UTC)

Of course Gibbons did not disprove anything. How would someone do that? The BBC report does not hold the same weight as a scientific study by a PhD in a peer reviewed journal. Gibbons concluded that suicide rates among those taking the drug were lower then suicide rates among those that did not get the drug. Thus, if the "controversy" served to scare people from taking anti-depressants, it may have caused more harm then good. The goal of the WP is to provide knowledge, not biased opinion. Disinformation can be dangerous.

You have repeatedly alleged bias in the article, but without support. It is not biased to report serious risks that even GSK now admits. Why do you call that "biased opinion" when it is proven fact admitted by the original manufacturer? You requested SkinWalker to lend input, but please see the discussion between SkinWalker and me above. Reliable sources report as scientific fact that the drug causes benefits and side effects; it would be biased to report one side but suppress the other. You seem to suggest _creating_ a bias by suppressing negative information, based on the possibility that the controversy "may have caused more harm then [sic] good," but that is the opposite of providing knowledge. At least you now seem to acknowledge that controversy exists, which should resolve the issue in this section.TVC 15 (talk) 19:36, 12 January 2009 (UTC)

You continue to avoid the issue I raised that the supposed "controversy" is exagerated and causes more harm than good. I have asked you three times to address the Gibbons study. You seem to prefer to rely on the BBC. Instead of attacking me or the grammatical errors in my arguments, will you please refute the Gibbons study? —Preceding unsigned comment added by 161.150.2.55 (talk) 20:26, 12 January 2009 (UTC)

I said Gibbons did not disprove the existence of a controversy. You said yourself, "Gibbons did not disprove anything." So, we agree. As for your suggestion that suppressing reliably sourced information might make some people better off, your argument is with WP generally, not me. And, please remember to sign your posts.TVC 15 (talk) 21:51, 12 January 2009 (UTC)

Why would Gibbons set out to disprove the existance of something? That is not possible. Let me quote Gibbons from the Am J Psychiatry "Suicide attempt rates were lower among patients who were treated with antidepressants than among those who were not, with a statistically significant odds ratio for SSRIs and tricyclics." Seems to resolves the controversy. The BBC is not as reliable as the Am J Psychiatry when it comes to psychiatry. Are you through playing games. While it is nice that the BBC compares SSRI's to cocaine, and doctor have prescribed cocaine in the past, it is not relevant to paxil. I am not claiming that there is no controversy, I am claiming that the controversy is over emphasized in the opening lines of the article. It should be relegated to the bottom of the article. Comparing paxil to cocaine, you are doing people are diservice with your scare tactics. —Preceding unsigned comment added by 161.150.2.55 (talk) 22:26, 12 January 2009 (UTC)

First, you are conflating paroxetine with SSRIs generally. As noted in the article, studies have shown paroxetine to be among the riskiest SSRIs (and less effective than competing products or lifestyle changes such as increased physical exercise). Second, whether reliably sourced facts are scary is not the issue. You might enjoy reading Dan Gardner's book "Risk," where he argues that after 9/11 people switched irrationally from airplane travel to automobiles, thus losing an additional 1,500 lives because airline travel is safer per mile than driving. However, unlike you, Gardner does not propose suppressing coverage of the facts (in this example, 9/11). Your argument is essentially the same as that of government censors and certain PR agencies: 'if we tell people this, it will lead them to make bad decisions (like voting for the opposition, or not buying our product), so we need to suppress it.' If facts scare you into irrational decisions, that may say something about you, but it does not justify suppressing facts from WP.TVC 15 (talk) 22:55, 12 January 2009 (UTC)

I'm not sure why the lead paragraph reference to controversy has suddenly become the subject of so much, umm, controversy. However, I have restored the key points: contrary to GSK marketing, which remains in the hands and minds of many prescribers, GSK now admits what so many (including FDA) had said for so long, i.e. the drug is habit forming (causes "serious discontinuation symptoms," aka withdrawal). Since GSK spent so much advertising the drug on TV as an anxiolytic that was "not habit forming," which was its key selling point compared to other anxiolytics, it seems appropriate to address the widespread misconception in the lead. Along the way, I removed two unsourced statements from the second paragraph. One was not even about paroxetine, and seemed instead to have been copied long ago from the Sertraline article. Please, WP is not an advertising venue, so before making edits that slant towards GSK's POV, check this discussion page to see if the topic has been addressed.TVC 15 (talk) 21:00, 14 January 2009 (UTC)

TVC 15 says "I have restored the key points: contrary to GSK marketing, which remains in the hands and minds of many prescribers, GSK now admits ..." This is not a key point about paroxetine. Perhaps this should go on the GSK page. Mwalla (talk) 22:57, 14 January 2009 (UTC)mwalla

Good luck with your efforts Mwalla. I gave up on this article some time ago, because someone has a serious case of WP:OWN over this article. I was also accused of being a shill for GSK. There's something about antidepressant articles that brings out the soapboxers. Skinwalker (talk) 23:41, 14 January 2009 (UTC)

This article has elicited many editors from all sides, but several editors have noted pro-GSK bias. As reliable sources continue to report the controversy surrounding previously concealed side effects of paroxetine, the information does not meet any of the definitions of soapboxing. However, edits that delete negative information in order to limit the article to happy talk ('the drug is popular, it helps all kinds of things, X million prescribers can't be wrong...') do meet that definition, especially example 5 (advertising).

It is a key point about paroxetine, because it relates directly to a difference between (a) reliably sourced facts and (b) widespread misinformation advertised by the original manufacturer. As the purpose of WP is to make knowledge available, a primary step is to address misinformation with accurate information. However, I appreciate your suggestion that the information should go on GSK's page. That page already has a section on the paroxetine controversy (and on that page the controversy is acknowledged to be a controversy). However, it would be a mistake to imagine that the controversy relates solely to the original manufacturer and not to the product itself. To the contrary, the mandatory black box warning and side effects of paroxetine apply equally to generic versions, regardless of manufacturer.TVC 15 (talk) 23:52, 14 January 2009 (UTC)

paroxetine vs. SSRIs generally

Mwalla, let's not revert each other and risk an edit war, let's try to focus on the facts and see if we can reach something that makes sense. The sentence that you restored about sertraline seemed to have been copied and pasted from the sertraline article. Maybe you want to use that article as a model for this one, but sertraline is a different drug, so sentences from that article can't just be copied and pasted without even changing the name of the drug. Likewise, statements about side effects in the paroxetine article need to be about paroxetine. I understand your reliably sourced statistics related to SSRIs generally, but the aggregate SSRI statistics include both better-than-average and worse-than-average drugs within the category. Paroxetine's unusually short serum half-life makes it particularly likely to cause withdrawal, a side effect for which it slowly became notorious despite the manufacturer's denials. The sentence about the drug's popularity is misleading without including the fact of addiction, because many of the people taking the drug reportedly feel involuntarily hooked on it.TVC 15 (talk) 18:56, 15 January 2009 (UTC)

Mwalla, your continued reverts are not productive. Let's try for balance and objectivity. Clearly the black box warning is important, for example.TVC 15 (talk) 19:27, 15 January 2009 (UTC)

It is still in the article. I will be here all day, try the veal. Mwalla (talk) 19:35, 15 January 2009 (UTC)mwalla

I am trying to find a compromise, and you're simply reverting. The issue is what goes in the introductory paragraph. If we are to include sales numbers (implying popularity), then balance requires including the fact that the drug is addictive. Also, the black box warning is an FDA mandate. Can you at least suggest an alternate wording that might move towards compromise?TVC 15 (talk) 19:40, 15 January 2009 (UTC)

Lets consult Skinwalker, Casliber, or someone else within the Pharmacogy project. Mwalla (talk) 19:43, 15 January 2009 (UTC)mwalla

There was already an anonymous 'request for help' on that project's discussion page, but it appears that even among people expressly interested in pharmacology, very few were willing to help paroxetine. Would you please address the issue of paroxetine vs. other SSRIs? And, given the huge advertising campaign in which GSK said paroxetine was "not habit forming," would you please explain why you think the now acknowledged withdrawal syndrome should be removed from the introduction? The cocaine article puts addiction in the intro paragraph, thus addressing the earlier misconception that cocaine was not addictive.TVC 15 (talk) 20:00, 15 January 2009 (UTC)

The dependence of drugs of addiction such as benzodiazepines and cocaine, heroin etc. is very different to the problems with SSRIs and it is misleading to use the word synonymously. In the former we see escalating usage and drug seeking behaviour. With SSRIs the problem is that there is a withdrawal syndrome. Use does not escalate nor does someone seek to use it, the main issue is the problems with stopping the medication. and yes they have been underreported historically and yes they are important. Casliber (talk · contribs) 23:08, 15 January 2009 (UTC)

To conclude, I object to the problem being dewscribed as "dependence" as it implies a connotation which is not applicable, but I am more than happy to have withdrawal and court cases in lead, though the tone may have to be more neutral. Casliber (talk · contribs) 23:10, 15 January 2009 (UTC)

Thanks for your comments. I appreciate your acknowledging the importance of the historically under-reported withdrawal syndrome, and the legitimacy of noting that and the court cases. The article text includes only one occurrence of the word "dependence," in a quote that was copied from the British Medical Journal. The connotations you listed are associated primarily with addiction. Although sources vary on the defining differences between addiction and dependence, for a drug that carries a withdrawal syndrome with "serious discontinuation effects," a neutral word is dependence, i.e. "a need for a substance so strong that it becomes necessary to have this substance to function properly."TVC 15 (talk) 23:27, 15 January 2009 (UTC)

balancing uses with side effects - see WP:NPOV

Mwalla, even a 30-second TV advertisement _for_ the drug would be required to warn of side effects. WP is supposed to provide a neutral article _about_ the drug. If you make the intro solely about the drug's benefits, but delete the side effects, then you're slanting WP even more than would be allowed in advertising.TVC 15 (talk) 21:30, 15 January 2009 (UTC)

My views

I was requested to add my views on here by Mwalla. Here they are. Paroxetine, is associated with suicide. It has for example side effects such as akasthesia and mania. Both conditions are well established as risk factors of suicide. A meta-analysis of trial data assuming there is no bias or conflict of interest, does not disprove that some patients become suicidal on paroxetine. All it proves is that people are more likely to become less suicidal rather than more suicidal. This is a limitation of meta-analysis, they do an overall interpretation of the data rather than an individual case by case analysis. Suicidal reactions to paroxetine are what is known as a paradoxical reaction. Paradoxical reactions can happen with virtually all drugs. For example, benzodiazepines can make someone more anxious, worsen seizures, make them more aggressive etc. As far as addiction goes. This is a more tricky and brings into debate, addiction versus dependence. I think that the BBC article was talking in terms of withdrawal related problems. Cocaine does not cause much of a withdrawal syndrome usually unless someone snorts the stuff all day every day for months on end. Paroxetine has a very low abuse potential but yet a fairly high risk of a withdrawal syndrome which can range from either mild to very severe. So paroxetine, does not have anything near the abuse and psychological addiction/dependence properties of cocaine but if talking in terms of a withdrawal syndrome then yes paroxetine is probably a worse offender. Perhaps that part needs to be reworded so that it is clear that it is talking about paroxetine being harder to get off of due to withdrawal symptoms than cocaine whilst also acknowledging that it has a low abuse potential. Patients need to be warned of the risks of acute side effects and withdrawal effects as well as the positive effects. The risks should not be played down or watered down, nor should the therapueutic benefits. I think that if the article includes both the positive and negative effects of the drug then that should be fine. Have a look at the benzodiazepine article, which has a good balance of the positive and negative effects of benzodiazepines.--Literaturegeek | T@1k? 22:04, 15 January 2009 (UTC)

Thank you and I agree that SSRI's are associated with suicide, primarily because suicidal people are often clinically depressed and prescribed SSRI's. If paradoxical reaction happen with all drugs, do all wikipedia drug pages contain a warning in the opening paragraph? The association with suicide remains in the article. SSRI's have not been shown to CAUSE suicide, which is the way TVC 15 makes it sound. My objection is with placing strongly worded warnings about suicide in the opening paragraph, as it may be counter productive. Clinically depressed people reseaching a medication that their doctors have prescribed do not need to be scared from taking it. See here:

http://ajp.psychiatryonline.org/cgi/content/abstract/164/7/1044 161.150.2.55 (talk) 22:10, 15 January 2009 (UTC)mwalla

Thanks Literaturegeek for your detailed and objective analysis. The Benzodiazepine article does describe dependence in the introduction: the first paragraph describes benefits, the second describes dependence. Also, as you say, a drug that reduces the risk of suicide in some patients may increase it in others; that seems especially likely where the drug is prescribed to people with (for example) generalized anxiety disorder and then causes suicidal ideation. The drug may prevent suicide in some patients but cause it in others. Also, paroxetine has been shown comparatively worse than other SSRIs in this respect, so the SSRI study cited by Mwalla above may not exonerate paroxetine specifically.TVC 15 (talk) 22:23, 15 January 2009 (UTC)

I believe that SSRIs have the potential to cause suicide in certain persons and prevent suicide in other patients and careful monitoring especially in the early stages of treatment and during dose reduction is required to minimise this risk. You have to disprove the well established correlation between mania and akasthesia and suicide before you can declare that drugs which can produce mania and akasthesia as side effects are not associated with suicide. I can accept that antidepresssants overall may reduce suicide statistically but this does not disprove individual people may be at risk of severe paradoxical reactions. Here is a simple example, you could take 1,000 people starving on an island, 10 of them are allergic to peanuts. You assign 500 people to placebo food and 500 to peanuts for 4 weeks. The results show that those who did not eat peanuts more often died of starvation whereas those who did eat peanuts lived. You could then meta-analyse this data and other similar studies and conclude that peanuts are in general a life saving food source for people in situations where they are short of food. However, this would not mean that anaphylaxis to peanuts does not occur in sensitive patients and that anaphylaxis to peanuts does not exist and that some patients would die from peanuts. Like I say the gibbons study does not disprove paradoxical reactions. There have been studies which show suicide and these have been widely reported in the media, especially in the UK. Infact GSK themselves did one study that showed increased suicide but this was in adolescents but still suggestive. Paroxetine is not only used in suicidal patients. People with anxiety disorders, OCD or moderate depression have taken it and reported suicidal reactions. As the drug has to carry a black box warning for suicide risk, I do not believe that there is undue weight by mentioning the suicidal properties in the lead.--Literaturegeek | T@1k? 22:34, 15 January 2009 (UTC)

Furthermore paradoxical reactions are not necessarily due to underlying disorders eg bipolar or whatever. Pharmacokinetic factors or just simply individual sensitivity to a drug can be the cause. Pharmacokinetic factors include metabolism and the half life. A slow metaboliser could have 2, or 3 or 4 times the blood level of someone who metabolises the drug quicker. This could lead to paradoxical reactions including altered mood, akasthesia, psychosis or mania with resultant suicidal tendencies. Equally like I say the antidepressant effects could via the therapeutic actions of the drug help someone with depression and prevent suicide.--Literaturegeek | T@1k? 22:40, 15 January 2009 (UTC)

One of the doctors in the gibbons study is financed by GSK, based on declarations of interest at the bottom of the full text paper. Whilst that does not disprove the findings, I thought that it was worth pointing out.--Literaturegeek | T@1k? 22:49, 15 January 2009 (UTC)

Literaturegeek says "I believe that SSRIs have the potential to cause suicide in certain persons " what is the source for this bold claim? The conflict of interest in the sceintific study mentioned did not preclude it from being published in a peer reviewed study. Lets review that study's main finding: patients receiving SSRI's had a lower incidence of suicide than those receiving a placebo. A warning about the association is appropriate for all SSRI's, not just paroxetine. There is adequate space devoted to this topic on the main page. Why are the risks of the medication given more emphaisis then the benfits? —Preceding unsigned comment added by 69.243.189.111 (talk) 00:16, 16 January 2009 (UTC)

FV has given a good explaination of the literature on SSRIs aand suicide below. Paradoxical reactions including suicide has been reported in the medical literature in adults but is controversial. On a personal note I have a friend who as an adult woman took paroxetine, only to treat nightmares she had which the doctor felt were anxiety induced so she wasn't very mentally ill or anything. Anyway within a week of taking paroxetine, she went off her head, shaved off all of her head, started hallucinating and hearing music and then ran into the sea to try and kill herself. She ended up as an inpatient in a psychiatric ward. She remained as an inpatient until her psychiatrist went on a week leave and saw a new psychiatrist who said that paroxetine was an evil drug and she had to come off of it. Only then did her mental state return to normal and she was discharged. I have heard of another person third hand who had a similar experience. So I have personal knowledge and also have read things in the literature and seen reports in the media. As far as the conclusions of the study saying that paroxetine reduces suicide rates, please reread what I typed above. Do I have to repeat myself? I clearly said that I accept that antidepressants may indeed overall, lower suicide rates. I never denied this! Please reread what I typed above. I am not retyping it again. As far as wiki weight,,,, maybe the benefits need to be spoken about more to get a better balance between positives and negatives and make the article more neutral.--Literaturegeek | T@1k? 21:14, 16 January 2009 (UTC)

Literaturegeek, I re-read what you typed above. Your personal beliefs and your experience with a friend are statistically insignificant in the face of peer reviewed scientific journals. Do I need to recount all of my experiences with patients on paroxetine? —Preceding unsigned comment added by 69.243.189.111 (talk) 22:01, 17 January 2009 (UTC)

Let's be clear here: the literature is inconclusive and itself mired in controversy (see e.g. PMID 15718537 and David Healy's response to the study). There is ample, seemingly reliable evidence that SSRIs may increase suicidality in children and adolescents (such as the now-famous Cochrane review Tim links to above); whether this extends to adults is, again, controversial. Many authors claim it does not; some claim it might, may, or does. There is controversy surrounding the use of clinical trial data vs. "real world" practice data. There is controversy regarding unpublished data and the bias created by under-publication of negative trials (which, unavailable, are not included in later meta-analyses). Wikipedia condenses, reproduces and reports the current state of knowledge on a subject. We can't introduce original research or draw conclusions from published research or collate data if reliable external sources haven't done so already. In a case such as this, when even the reliable sources upon which this article should be built have been called into question (perhaps rightly so, perhaps not), all we can do is present a balanced picture of the current situation. I don't think we should be leaving any definitive or strongly worded statements in the article body; there are no definitive, cut-and-dried conclusions in the literature. Fvasconcellos (t·c) 13:04, 16 January 2009 (UTC)

Fvasconcellos, thanks for linking to the PMID study. Further, the New York times reported here that suicide rates were highest before treatment and declined after treatment began. http://www.nytimes.com/2007/07/10/health/psychology/10depre.html Let's us bring in more interested users with knowledge of the current literature. I do not want to surpress the controversy, I want it placed in a subsection, not the opening paragraph as it was originally the fourth sentence. Mwalla (talk) 13:39, 16 January 2009 (UTC)mwalla

I see the lead is still being edited and reverted without discussion. Please, will everyone keep to the Talk page for now? Fvasconcellos (t·c) 22:25, 18 January 2009 (UTC)

Protection

I've protected the article due to edit-warring. I'm not going to block anybody this time, but if this edit warring resumes once the temporary protection ends, lengthy blocks will be entirely appropriate.

Some useful sources to guide your discussion of this point would be PMID 17636776 and PMID 18345955, if anybody needs full-text of these articles please e-mail me. Tim Vickers (talk) 23:17, 15 January 2009 (UTC)

I appreciate the sharing of all of the current journal articles in this discussion. Statistical testing and proving significance is difficult in this field. "Selective serotonin reuptake inhibitors (SSRIs) for depressive disorders in children and adolescents" linked to by Tim above is essentially inconclusive, in part due to statistical complexity. An additional study by Gibbons concludes "Results of our analysis of the FDA AERS data revealed that newer antidepressants are associated with lower rates of suicide adverse event reports compared with older antidepressants. " although it does not appear that this study targetted adolescents. I may be wrong. Mwalla (talk) 21:54, 16 January 2009 (UTC)mwalla

I goofed with the lead

In trying to model the lead on sertraline, I introduced some wrong info, which an IP picked up. I have corrected - paroxetine has more anticholinergic activity than other SSRIs. Apart from that, I think it flows nicer now. Casliber (talk · contribs) 09:42, 16 January 2009 (UTC)

Sertraline's lead: "Due to the rarity of this side effect, statistically significant data is difficult to obtain, and suicidality continues to be a subject of controversy." is inappropriate for paroxetine. We should replace it with: “Paroxetine is associated with a statistically significant increase in the risk of suicidal tendencies in both adults and children.”

The fact that paroxetine increases suicidality of children is beyond any doubt, and there is a special report by MCRA on that matter (I am trying to find the ref).

In other respects, I consider a recent systematic analysis of published and unpublished trials of paroxetine in the Canadian Medical Association Journal (PMID 18227449, free access) as definitive:

"The present analysis,which suggests that paroxetine is associated with a statistically significant increase in the risk of suicidal tendencies, expands the results of previous re-analyses of GlaxoSmithKline data.16,17 In particular, in the analysis carried out by Glaxo-

SmithKline of suicide attempts by adults with major depression, the frequency was higher among patients who received paroxetine than among those who received placebo (11/3455 v. 1/1978; OR 6.7, 95% CI 1.1–149.4).27 The recently released re-analysis by the US Food and Drug Administration of 372 placebo-controlled antidepressant trials involving almost 100 000 patients with any psychiatric disorders confirmed these figures by showing that, among the selective serotonin reuptake inhibitors and newer antidepressants, only paroxetine was significantly associated with an excess risk of suicidal behaviour (US Food and Drug Administration codes 1, 2 and 3) (OR 2.76, 95% CI 1.16–6.60).19" 71.244.121.113 (talk) 12:54, 17 January 2009 (UTC)

Interesting. There are still problems that are frustrating in trial design with selection of patients etc. - milder cases, not using people who voice suicidal ideation. etc. Anyway, as it is a metaanalysis and not a review article, we should word it to reflect the source. Casliber (talk · contribs) 14:08, 17 January 2009 (UTC)

Works for me. As you can see from the above excerpt, the results of CMAJ analysis simply confirm the results of another 3 analyses including the ones by the FDA and GSK itself. So they seem to be uncontroversial. 71.244.121.113 (talk) 15:20, 17 January 2009 (UTC)

Is the Canadian Medical Association Journal as prestigous a journal on the topic of psychiatry at the American Journal of Psychiatry? The CMAJ Besides, I think the conclusion of the paper is misquoted. Here is a quote from an editor of the journal about the reference paper: "I was disappointed and puzzled by the bizarre primary outcome measure selected by the authors: the proportion of patients who left a study early for any reason. Consider the ideal situation in which no one in either study arm drops out; it would be impossible for the active treatment to be better than placebo even if all treated subjects went into remission. How can this be a measure of effectiveness?

In my practice, the biggest challenge is persuading patients to persist with therapy through the first few days of unpleasant side effects until the beneficial effects become manifest. I consider early dropout to be a failure of my persuasive powers and not an indication that the therapy is ineffective. I believe that it is important to distinguish between dropout in the first days of treatment, which is a consequence of the predictable and often transitory unpleasant side effects, and delayed dropout, which may reflect treatment failure. The authors failed to stratify their analysis on the time of dropout and their analysis is thus not informative with respect to dropout for the important end points of treatment failure or persistent side effects.

As a clinician I am primarily interested in the effectiveness of a drug in those who actually take it. It is thus disappointing that the authors gave short shrift to their secondary outcome measures, all of which showed a significant benefit of active treatment."

This sentence "A large systematic review of published and unpublished randomised trials showed that paroxetine is associated with a statistically significant increase in the risk of suicidal tendencies in both adults and children." should be vetted in this discussion before it goes in the main page. Instead of putting words in the mouths of the authors, why not use the actual conclusion from the study:

Paroxetine was more effective than placebo, with fewer patients who did not experience improvement in symptoms of at least 50% —Preceding unsigned comment added by 69.243.189.111 (talk) 00:59, 18 January 2009 (UTC)

No the analysis was not misquoted."The present analysis,which suggests that paroxetine is associated with a statistically significant increase in the risk of suicidal tendencies, expands the results of previous re-analyses of GlaxoSmithKline data." Nobody doubts that paroxetine is better than placebo, and that is reflected in its indications and in the main text. However, suicidality is a troublesome and serious side effect and should be also reflected in the lead. No "vetting" is required for writing in WP. 71.244.121.113 (talk) 01:39, 18 January 2009 (UTC)

Paroxetine is associated with a clinically significant weight gain

I would like to change the sentence "however, it has a more pronounced anitcholinergic effect and may cause weight gain." to "Paroxetine is associated with a clinically significant weight gain".

I would like to skip mentioning the mechanism. While the anticholinergic effect of paroxetine may be responsible for the weight gain, it is hypothetical, since the M3 inhibitory properties of paroxetine are relatively weak.

The studies on paroxetine and weight gain are nicely summed up by Papakostas in his recent review in Journal of Clinical Psychiatry (PMID 18494538. Sorry, folks, no public access to this one.)

"34-week clinical trial27 comparing the SNRI duloxetine (40–120 mg/day) with the SSRI paroxetine (20 mg/day) and placebo reported that both paroxetine and duloxetine treatment were more likely to result in weight gain than placebo. The incidence of >7% body weight gain was 3.1% among placebo-treated patients, 10.8% among duloxetine-treated patients, and 13.8% among paroxetine-treated patients. Thus, it appears that there may be differences among SSRIs in the risk for weight gain during long-term treatment. In fact, a study28 involving the treatment of MDD with the SSRIs paroxetine, fluoxetine, or sertraline reported weight gain of 7% or greater by 25.5% of patients taking paroxetine for 26 to 32 weeks. Conversely, only 6.8% of patients taking fluoxetine and 4.2% of patients taking sertraline experienced clinically significant weight gain in that study." A note of explanation - 7% is generally considered to be a cut-off for a clinically significant weight gain. Over a year or two 3-7% of patients would show such a weight gain on placebo. So 4% on sertraline and 7% on fluoxetine are not much different from normal, while 25% on paroxetine is huge. 71.244.121.113 (talk) 15:37, 17 January 2009 (UTC)

I don't think the wording was meant to imply that anticholinergic effects cause weight gain, just note that a) paroxetine has relatively pronounced anticholinergic effects, and b) may cause weight gain. I agree it should be reworded. Fvasconcellos (t·c) 17:10, 17 January 2009 (UTC)

Is efficacy of paroxetine for depression similar to that of older tricyclic antidepressants?

Is efficacy of paroxetine for depression similar to that of older tricyclic antidepressants? - It may well be. However, one study I know about - (PMID 2140382) indicates that it is not so. Are there other studies, more positive for paroxetine? Until we have those refs, maybe we need to remove this equal efficacy statement. 71.244.121.113 (talk) 16:03, 17 January 2009 (UTC)

A Cochrane Review is in the works. Meanwhile, this is an excellent source for comparisons with other newer antidepressants. PMID 10760555 may be useful but I'd have to see the full text (or perhaps a kindly soul will have a look themselves? [waves at Cas, Tim) Fvasconcellos (t·c) 17:28, 17 January 2009 (UTC)

Thank you. According to the paper you recommended, tricyclic antidepressants showed trend (close to statistical significance p=0.07) to be more efficacious than paroxetine. The questionable introductory sentence should be re-written. 71.244.121.113 (talk) 01:19, 18 January 2009 (UTC)

An anonymous URL changed that sentence from "less effective" to "more effective;" I followed the links and ended up compromising on "comparable.".TVC 15 (talk) 08:07, 26 January 2009 (UTC)

CMAJ study

An anonymous URL (161.150.2.55) removed a quote from the introductory paragraph stating, "The CMAJ study is essentially discredited by the editor of the CMAJ in the same issue." However, the edit left in place a summary of the study's pro-paroxetine findings. If the study is discredited, then it should not be quoted at all. I will remove the sentence here so the issue can be sorted out.

For major depression, a large systematic review of published and unpublished randomised trials showed that paroxetine was more effective than placebo, with fewer patients who did not experience improvement in symptoms of at least 50%; however, the same review found, "Among adults with moderate to severe major depression in the clinical trials we reviewed, paroxetine was not superior to placebo in terms of overall treatment effectiveness and acceptability."

And, please remember to sign in, and discuss here rather than anonymously changing the article.TVC 15 (talk) 20:44, 26 January 2009 (UTC)

Ends vs. Means

This article and accompanying discussion seem to have evolved through three stages. The article seems to have started out with pro-GSK bias that many above suspected was written by GSK and/or its public relations firm(s). Predictably, that led to a backlash, and some people seem to have a negative view of drugs generally and everyone who makes or sells them. Now, we seem to have entered a third stage, perhaps related to the increase in suicides during the years after the FDA's black box warning; some users from WP's pharmacology project and some anonymous URLs seem to be trying to rehabilitate SSRIs generally including paroxetine specifically. Sadly, some of these users (Mwalla and at least one of the anonymous URLs) act as if "the ends justify the means," i.e. if you put paroxetine in the water supply, the total number of suicides might be reduced, thus lives would be saved, and we should silence any contrary information to save lives. In trying to defend reliably sourced information, I personally have been falsely accused of all kinds of things, when in fact I am just trying to maintain WP:NPOV balancing positive and negative reliably sourced information. Every drug has side effects, and every FDA-approved drug has some proven benefits. Wikipedia is not a sales tool for drug companies or clinicians, no matter how well intentioned, to shepherd customers into making what someone else thinks is 'the right decision' or what's best for them. Wikipedia is about accurate, reliably sourced information, which readers can use in making their own decisions. Please, let WP report objectively.TVC 15 (talk) 21:07, 26 January 2009 (UTC)

The increase of suicides in the US in 2004 was nothing but a statistical blip. In the following 2005 the number of suicides decreased (see doi: 10.1176/appi.ajp.2007.07091467). The MHRA report on the safety of SSRI's issued in December 2004 was skeptical about the attempts to interpret the suicide rates in any way: "A range of factors influence population suicide rates. It is therefore challenging to distinguish the discrete effects of increased antidepressant prescribing from changes in other risk factors. Furthermore, declining overall suicide trends may mask rises in some age/sex groups. In Australia, recent rises in antidepressant prescribing were associated with declines in suicide in some age/sex groups but with increases in others. In Britain, declines in suicide preceded increases in prescribing, and rises in antidepressant prescribing since 1991 in different age/sex groups do not consistently coincide with clear changes in previous suicide trends." (see www.mhra.gov.uk/home/groups/pl-p/documents/drugsafetymessage/con019472.pdf, p. 71). 71.244.121.113 (talk) 02:49, 27 January 2009 (UTC)

161.150.2.55 is back, and illustrates what I mean. Previously, 161.150.2.55 deleted the CMAJ review's conclusion that overall effectiveness and acceptability was no better than placebo, but tried to lead the article with a pro-paroxetine finding cherry-picked from the same review. 161.150.2.55 expressly argues in favor of bias because reliably sourced facts are "scary" and might complicate clinicians' sales pitches, so the information must be deleted to save lives. 161.150.2.55's factual assumptions are false as demonstrated by 71.244.121.113 above, and the (il)logic is totally misplaced on Wikipedia. WP is not about hiding information in order to collude in manipulating people into what 161.150.2.55 claims is best for them. WP is about making reliably sourced information freely accessible.TVC 15 (talk) 01:07, 28 January 2009 (UTC)

TVC, just because someone disagrees with you does not make them pro-bias, manipulative, or unobjective. Unless you can stop imputing sinister motives to your fellow editors I will initiate dispute resolution. Skinwalker (talk) 17:21, 31 January 2009 (UTC)

Responsibilities elsewhere have delayed my reply to the comment immediately above, but the reply belongs here. I continue to assume good faith, and Skinwalker is sometimes right, but the 'straw man' argument above strains credulity. I never suggested that merely disagreeing with me about something means any of the things Skinwalker listed. Rather, MWalla and 161.150.2.55 have _stated_ their _goal_ is to bias the article in order to manipulate people: specifically, to suppress reliably sourced information because such "scary" facts might discourage people from taking the drug. As Skinwalker has acknowledged, and as linked studies and reviews have found, there are better anti-depressants (and non-drug therapies that are also better than paroxetine). As has been widely reported elsewhere, the sales pitches of prescribers are frequently influenced by drug makers' marketing, including sometimes direct payment.[13] WP provides a rare forum for objective, reliably sourced information without financial bias, and honest debate may lead to canceling out other biases as well. To move the discussion forward, I would be very interested if someone can find reports on what paroxetine is actually prescribed for. I suspect that paroxetine may be prescribed primarily as an anxiolytic, which would make MWalla and 161.150.2.55's arguments (which have already been disproved by 1.244.121.113), and references to depression, less relevant.TVC 15 (talk) 00:25, 10 February 2009 (UTC)

Skinwalker has made a number of changes to the article. On the whole, I think these changes are good. I am sure some will disagree, but I think his approach was balanced. We need to inform people of facts and let the decide for themselves. Paroxetine is a chemical. It helps some people. It does not help others. People with clinical depression and anxiety disorders need help. Do not scare them away from following their doctor's advice. Until mental health care improves, paroxetine is a valuable tool. It is not a cure all but then again, the clinically depressed used to be treated with much harsher "solutions" such as imprisonment or torture. —Preceding unsigned comment added by 24.15.179.168 (talk) 03:07, 1 February 2009 (UTC)

Thank you. Let me make my intentions clear:

• This article should not give the impression that paroxetine is an uncontroversial cure-all for depression. It is not. Like tricyclic antidepressants, it is no longer considered a first-line treatment for clinical depression. It can have serious side effects. There has been controversy over its side effects and marketing, and the article should neutrally represent this.
• On the other hand, the fact that there are negative side effects is not a reason to use "scare quotes", nor to represent SSRI discontinuation syndrome as a sign of drug addiction when addiction specialists have determined it is not, nor to give undue weight to the point of view that some evil corporation intentionally released a hysterically dangerous drug onto an unwitting populace. I mean, come on, SSRIs are not thalidomide.
• Most SSRIs have side effect profiles similar to paroxetine. Most other articles on pharmaceutical drugs neutrally present both the positive and negative consequences, and do not attempt to give readers medical advice.
• This article should rely on the best available sources, namely metaanalysis articles and reviews published in medical journals. In the near future I will review the sources of this article and prune those that do not meet these standards.

I invite review and discussion of my contributions. However, I will not put up with accusations that I am shilling for GlaxoSmithKline or trying to whitewash the article of criticism. Yes, paroxetine has been correlated with an increased incidence of suicidal ideation. So have pretty much all modern antidepressants. Without sounding heartless, sufferers of clinical depression (of which I am one) tend to think about offing themselves. Yes, it can cause a nasty discontinuation syndrome. These items should be discussed in the article, but should not take prevalence over a neutral discussion of the drug's benefits and risks. Skinwalker (talk) 03:40, 1 February 2009 (UTC)

Skinwalker, thank you for your very nice summation of what is wrong with the article and how it should be put right. I support almost every point you bring up. All the changes you made to the article so far have been excellent. I hope you also agree with a little cleanup I did with the side effects part. On the other hand, TVC15 is also right, and so far has not made any bad changes to the article.

Until very recently I would have also subscribed to your ridicule of the "point of view that some evil corporation intentionally released a hysterically dangerous drug onto an unwitting populace. I mean, come on, SSRIs are not thalidomide." However, the revelations that came in 2008 about the misconduct of leading medical researchers and of the best pharmaceutical companies left me aghast. For example, the editorial in a neutral "Journal of Neurology" states that GSK and the researchers may have suppressed the suicide risk data in paroxetine trials.

Nemeroff got $2 million and never reported it. How would you treat the reviews and meta-analyses he conducted? What about the work of Thase and Montgomery who are also known for having tight relationships with the industry?

An editorial in JAMA in April 2008 entitled "Impugning the Integrity of Medical Science. The Adverse Effects of Industry Influence." goes on to describe "how Merck may have misrepresented the risk-benefit profile of rofecoxib in clinical trials involving patients with Alzheimer disease or dementia. The authors show that the company’s report to the FDA appears to have attempted to minimize the mortality risk by using an “as-treated” analysis, whereas an internal analysis conducted by the company several months earlier and using the correct intention-to-treat analysis provided evidence of a significantly increased mortality risk among patients assigned to receive rofecoxib." 71.244.121.113 (talk) 12:21, 1 February 2009 (UTC)

The editorial in the Journal of Neurology is a reliable source, and we should use it. Your paraphrase above is a good summation. The situation with Nemeroff is somewhat complicated. On one hand, I am personally appalled at his lack of disclosure, and I expect the NIH to yank any remaining grant funding he retains. On the other, it is really, really hard to find any pharmacological research that does not have some relationship with industry. I would not use Nemeroff's papers in this article, but I would judge others on whether or not there is evidence of a "smoking gun", i.e. are there allegations in a reliable source that a researchers' judgement is compromised? Can you provide a similar source for Thase and Montgomery? I don't think simply taking research money is a cause for concern, but proven lack of disclosure (extreme in Nemeroff's case) or similar shenanigans on the part of the authors do impeach sources IMO. As for rofecoxib (better known as Vioxx), that's an altogether different drug. However, our article on rofecoxib neutrally reports what reliable sources, mostly medical journals, have said on the topic (which is pretty damning) without resorting to polemics. This article should meet that standard as well. Skinwalker (talk) 13:13, 1 February 2009 (UTC)

Arbitrary break. How to treat conflicts of interests

My main point is that, unfortunately, evil corporations and unscrupulous researchers do exist, and this has practical implications for this article. For example, a meta-analysis of paroxetine vs tricyclics conducted by Montgomery finds that they are equal (http://cat.inist.fr/?aModele=afficheN&cpsidt=972015). A meta-analysis by Anderson finds that tricylics are likely to be more efficacious than paroxetine.(PMID 10760555) Say, I can find a disclosure from Montgomery stating that he has financial ties with GSK. Anderson does not have any ties with GSK. Should we treat the Anderson's analysis as more valid? Should we leave Anderson's conclusion in the lead and mention Montgomery's analysis only in the body of the article as unreliable? 71.244.121.113 (talk) 14:16, 1 February 2009 (UTC)

We should report both, e.g. "One metaanalysis says X, the other says Y.". Let the reader decide. I don't think either belong in the lead. As I said above, financial ties are not sufficient to disqualify a source if there has not been significant criticism of that specific researcher, as there has been in Nemoff's case. If you like, we can ask for a third opinon on how to treat sources that may or may not have financial conflicts. Skinwalker (talk) 19:44, 1 February 2009 (UTC)

There have been significant criticism of Stuart Montgomery. For example, The Guardian (http://www.guardian.co.uk/society/2004/oct/04/health.businessofresearch) describes how Montgomery was sitting on the Committee on the Safety of Medicines, which was deciding whether to approve sertraline. And at the same time Montgomery was advising Pfizer (the sertraline manufacturer) on the best course of action to overcome the committee doubts. Does that disqualify him? If not, I can probably find more. 71.244.121.113 (talk) 22:34, 1 February 2009 (UTC)

In another example, in 1995 Stuart Montgomery signed an article, an analysis of paroxetine trials, which concluded that paroxetine decreases suicides 6-fold (see PMID 7613102). Later, Montgomery's co-author David Dunner, admitted that the paper was ghostwritten by Glaxo. (see http://www.guardian.co.uk/Archive/Article/0,4273,4351264,00.html) 71.244.121.113 (talk) 23:13, 1 February 2009 (UTC)

Who cares who writes the research? If you do not trust the research, replicate the expirement yourself. If it is sceintific research, use it. Everyone has a bias. Psychologists are biased against medication. Liberals are biased against "evil corporations". It is not likely that millions of patients, doctors, and scientists are in a mssive conspiracy to trick people into taking paroxetine. What is likely, is that drug companies try to find a product which people are willing to pay for. It is called capitalism. Sometimes fraud happens... but there is no scientific evidence of that in the case of paroxetine. —Preceding unsigned comment added by 161.150.2.55 (talk) 15:11, 2 February 2009 (UTC)

Is the US Senator Chuck Grassley, Republican from Iowa, a liberal? He posted on his official website a report detailing Glaxo misdeeds in concealing paroxetine side effects (see http://finance.senate.gov/press/Gpress/2008/prg061208a.pdf). 71.244.121.113 (talk) 01:04, 3 February 2009 (UTC)

Last I checked, Chuck Grassley is not a medical doctor. Would you take George Bush's opinion on embryonic stem cells? —Preceding unsigned comment added by 161.150.2.55 (talk) 14:33, 3 February 2009 (UTC)

Grassley is a conservative. He is one of the senior members of the Senate. His attention to the problem of the conflict of interests means that it is serious. The actual report (http://finance.senate.gov/press/Gpress/2008/prg061208a.pdf) was written by Joseph Glenmullen, a professor of psychiatry at Harvard University. Here is an excerpt from Grassley's press-release: "Senator Chuck Grassley has asked the Food and Drug Administration to carefully scrutinize information it received from drug maker GlaxoSmithKline about the anxiety disorder drug Paxil, based on the contents of a newly available report about the drug’s risk for suicide among adults. Grassley also asked the FDA to review findings released earlier this year by the British drug-safety agency which charged that the drug maker has known about suicide risk with pediatric use of Paxil since 1998. The report cited by Grassley was prepared by Dr. Joseph Glenmullen, a professor of psychiatry at Harvard University. The report asserts that GlaxoSmithKline had to know of Paxil’s suicide risk when it sought FDA approval for the drug. The Glenmullen report was recently released from under court seal by a Kansas judge. It is posted with this news release at finance.senate.gov. Grassley asked GlaxoSmithKline about the Glenmullen report last February. Weeks later, the British Medicines and Healthcare products Regulatory Agency released its own report that was four years in the making.“The British counterpart to our country’s FDA found that GlaxoSmithKline withheld important safety data on Paxil," Grassley said. "If the company engaged in this behavior in the U.K., then I want to make sure that the same didn't happen here in the U.S. The FDA should investigate this question thoroughly and be forthcoming about its findings." (http://finance.senate.gov/press/Gpress/2008/prg061208.pdf) 71.244.121.113 (talk) 01:07, 5 February 2009 (UTC)

The Glenmullen report was commissioned by lawyers pursuing cases against GSK. But nobody ever reports that conflict of interest! —Preceding unsigned comment added by 86.154.37.130 (talk) 00:10, 12 February 2009 (UTC)

Are side effects of paroxetine treatment frequent?

The side effects of paroxetine treatment are frequent. There is nothing alarmist about that, and in that respect paroxetine is not much different from other SSRIs. The following information is taken from the Paxil Prescribing Information . 20% of patients treated with paroxetine in the clinical trials for major depressive disorder discontinued due to the side effects. Among the most frequent treatment-emergent side effects in the trials for MDD were: nausea (26% on paroxetine vs 9% on placebo), somnolence (23% on paroxetine vs 9% on placebo, ejaculatory disturbance (13% on paroxetine vs 0% on placebo), other male genital disorders (10% on paroxetine vs 0% on placebo), asthenia (15% on paroxetine vs 6% on placebo) and sweating (11% on paroxetine vs 2% on placebo). 71.244.121.113 (talk) 15:04, 31 January 2009 (UTC)

Is 10% frequent? I would say frequent is >50%. Suicide is "common" amongst the clinically depressed. Paroxetine reduces this risk. When it comes to side effects, the good side effect of no suicidie trumps the bad side effect of nausea. Doctors are in the best position to weigh the risk of suicide vs. the risk of diarrhea. In the US, you can't get paroxetine without a consultation with a doctor.

Also, what is an ejaculatory disturbance? Is that like a nocturnal emission?

In response to the vandal:

"In efficacy trials, on average, 61 percent of patients experienced at least one adverse event during treatment. Nausea, headache, diarrhea, fatigue, dizziness, sweating, sexual dysfunction, tremor, dry mouth, and weight gain were the commonly reported adverse events. Overall, second-generation antidepressants led to similar adverse events." (Report by The US Agency for Healthcare Research and Quality on Comparative Effectiveness of Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression at http://effectivehealthcare.ahrq.gov/repFiles/Antidepressants_Final_Report.pdf)71.244.121.113 (talk) 00:52, 3 February 2009 (UTC)

Lets be clear, "side effects" such as nausea are insignificant compared to the "side effects" of clinical depression, for which paroxetine has been known to reduce. Individually, most patients find these side effects tolerable. Naturally, if you are not clinically depressed or suffer from severe anxiety, do not take paroxetine. As always consult your doctor. As for teenagers, there is no statistically accurate proof that suicide is caused by the drug. "suicide ideation" is not easily quantified, therefore there is as yet no proof that paroxetine causes suicide nor suicide ideation. In fact, paroxetine reduced the incidence of actual suicides. http://www.cleveland.com/nation/index.ssf/2008/11/after_2_decade_decline_teen_su.html

Statistically significant risk of suicidality with paroxetine

PMID 18227449: "Significantly more patients in the paroxetine group than in the placebo group left their respective studies because of side effects (random effect RR 1.77, 95% CI 1.44–2.18) or experienced suicidal tendencies (odds ratio 2.55, 95% CI 1.17–5.54)." "The present analysis, which suggests that paroxetine is associated with a statistically significant increase in the risk of suicidal tendencies, expands the results of previous re-analyses of GlaxoSmithKline data.16,17 In particular, in the analysis carried out by GlaxoSmithKline of suicide attempts by adults with major depression, the frequency was higher among patients who received paroxetine than among those who received placebo (11/3455 v. 1/1978; OR 6.7, 95% CI 1.1–149.4).27 The recently released re-analysis by the US Food and Drug Administration of 372 placebo-controlled antidepressant trials involving almost 100 000 patients with any psychiatric disorders confirmed these figures by showing that, among the selective serotonin reuptake inhibitors and newer antidepressants, only paroxetine was significantly associated with an excess risk of suicidal behaviour (US Food and Drug Administration codes 1, 2 and 3) (OR 2.76, 95% CI 1.16–6.60).19" 71.244.121.113 (talk) 01:50, 5 February 2009 (UTC)

Review and evaluation of clinical data: relationship between psychotropic drugs and pediatric suicidality, p 30, author Hammad TA, date 2004-08-16, work Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and Pediatric Advisory Committee. September 13 - 14, 2004. Briefing Information.; publisher = FDA. (http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4065b1-10-TAB08-Hammads-Review.pdf): "Paxil, all indications (Fixed effect model), Suicide Behavior or Ideation [codes 1, 2, & 6], Risk ratio (95% CI) = 2.65 (1.00,7.02). Note that the signal is suggested in both the MDD and the non-MDD trials." 71.244.121.113 (talk) 02:10, 5 February 2009 (UTC)

There is a difference between suicide and suicide ideation. Paroxtine lowers the risk of suicide in adults. There is not proof for the effects on teenages, but studies suggest teen suicide has increased since the addition of blackbox warnings. —Preceding unsigned comment added by 161.150.2.55 (talk) 14:19, 5 February 2009 (UTC)

That is exactly what the paragraph you keep vandalizing used to say: "increase in suicidal tendencies". You must not change the information based on several references and replace is by your own unsupported opinion. 71.244.121.113 (talk) 11:21, 6 February 2009 (UTC)

Placebo v antidepressants

What are people's views on this paper? Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration--Literaturegeek | T@1k? 15:58, 5 February 2009 (UTC)

Thanks for the link. I think it underscores the fact that anti-depressants are medcations intended to treat serious illnesses, such as clinical depression. They are not intended to treat a case of "the Mondays".  :) To quote the article " The difference in improvement between the antidepressant and placebo reached clinical significance, however, in patients with initial HRSD scores of more than 28—that is, in the most severely depressed patients. " —Preceding unsigned comment added by 161.150.2.55 (talk) 21:52, 5 February 2009 (UTC)

Since the lead author has received income from Squibb and Pfizer, who manufacture drugs that compete with the four antidepressants discussed in the article, I'd say it's clearly biased and unusable. Skinwalker (talk) 23:53, 5 February 2009 (UTC)

Good point Skinwalker! I read this study by Kirsch previously, and although I noticed that antidepressant sertraline (Pfizer) was not included into the analysis for spurious reasons, I never linked that with the lead author getting money from Pfizer. Some secondary conclusions of the study are bizarre. On the other hand, we may go easy on Kirsch: the conclusions of the study are broadly anti-antidepressant so they are harmful for all manufacturers. In addition, another, broader and more careful analysis by Turner (PMID 18319297.), reached the same main conclusion, although Turner's interpretation is much more objective. 71.244.121.113 (talk) 03:15, 6 February 2009 (UTC)

I was being somewhat facetious about not using this source. I find your desire to include this source - which favors the view you've been advocating - while deprecating other sources to be inconsistent with WP:NPOV. Each of the sources we've discussed have financial connections with industry. Why should we favor one over the other? We are likely not going to be able to find medical references whose authors have not taken funding from pharmaceutical companies. We have a duty, per NPOV, to report all notable views on a topic. Each source should be discussed in the article. Each source should be linked externally so that readers can see the financial disclosures on the papers.

I strongly suggest you reconsider your approach to editing this article. To paraphrase what you've said above, is is inappropriate to push conclusions that "are harmful for all manufacturers". Advocacy is frowned upon here, as is the exclusion of reliable and verifiable sources. You're going to have a tough time here if you can't follow these policies. Skinwalker (talk) 18:19, 7 February 2009 (UTC)

Also, Turner states: "In contrast to Kirsch and colleagues’ conclusion that antidepressants are ineffective, we concluded that each drug was superior to placebo."[14] I can't see how this represents the same main conclusion as Kirsch, as you state above. Turner found that certain antidepressants were less effective than is apparent from journal articles, not that these drugs were inferior to placebo. Skinwalker (talk) 18:44, 7 February 2009 (UTC)

Why did you decide that I want the Kirsch paper included? I was actually critical about it. As I said, Turner's paper is much better. Regardless, neither one belongs to this article because paroxetine was combined with other antidepressants within those meta-analyses. Both papers have been objectively reflected in Treatment for depression#Efficacy of medication and psychotherapy. Let me repeat myself: antidepressants are more effective than placebo. The devil is in the details, that is, in the balance of benefits and side effects. It is a general consensus in the psychiatry, and I believe you agreed with it in one of your posts, that escitalopram, sertraline and fluoxetine offer a better balance of risks and benefits. Accordingly, they are prescribed more often, as well. I really have no disagreements with you. 71.244.121.113 (talk) 21:30, 7 February 2009 (UTC)

On an unrelated note, what is your opinion about 161.150.2.55 edits. Do they constitute vandalism? 71.244.121.113 (talk) 03:15, 6 February 2009 (UTC)

Well, vandals don't usually stick around on the talk page to discuss their edits. The paper he or she is concerned about is poorly written (from a grammatical standpoint, at least) and puts forth contradictory conclusions at times. I myself read it and couldn't figure out if it was saying suicidal tendencies increase or decrease, and whether it was with the control or test groups. Probably just need to read it closer. I'm uncomfortable describing this as vandalism. Response to your other point later. Skinwalker (talk) 11:34, 6 February 2009 (UTC)

I checked the definition of vandalism on WP:VANDAL, it is someone who deliberately compromises the integrity of Wikipedia. In this case 161.150.2.55 changes "statistically significant increase in suicide" to "statistically significant decrease", without changing references. This creates a false impression that the references support "decrease" while they actually support "increase". Another type of vandalism includes addition of obscenities or crude humor , which 161.150.2.55 also did here [15]. 71.244.121.113 (talk) 00:58, 7 February 2009 (UTC)

Please stop referring to this editor as a vandal, and discuss instead whether the reference supports his conclusion or yours. As for the "crude humor", SSRIs have sexual side effects and can be used to treat premature ejaculation, so his comment to that respect was not off-topic or out of line. Skinwalker (talk) 18:19, 7 February 2009 (UTC)

Skinwalker, I would agree that the paper is not the best. However, I would not conclude that because someone received money from a drug company, that their research is biased. We should not assume bias or lack of bias. We as readers need to be unbiased in our assesment, make sure they follow scientific method, and look to see if their results can be confirmed with evidence from others sources. We know that in mass media, sensationalism sells newspapers, therefore are all news stories sensationalist? If the BBC does an investigation into Paroxetine, are they likely to report that "it works great, no news here"? —Preceding unsigned comment added by 161.150.2.55 (talk) 15:37, 6 February 2009 (UTC)

With the edit block on the page, that user is a certified vandal now. 71.244.121.113 (talk) 21:30, 7 February 2009 (UTC)

See my response above. Each source should be discussed in the article so that the reader can come to their own conclusion. Skinwalker (talk) 18:19, 7 February 2009 (UTC)

Edit warring

There are some edit wars going on here. I've full protected the page 1 week, rather than semi-protecting, as both IP users and logged in users are involved--semi would be an unfair advantage to the logged in users, and that's not what protection is for in a content dispute. Please hash this stuff out on this talk page, or else the protections will likely grow in duration, and then no one will be able to unfortunately edit this page. rootology (C)(T) 17:14, 7 February 2009 (UTC)

Paroxetine has no dependence potential

I would like to question the subchapter "=Dependence" inserted recently. It is based on a poor quality evidence. The study quoted (PMID 12369270) interviewed 54 "antidepressant users". It does not specify what antidepressants were used, and paroxetine is not mentioned in the article even a single time. The study participants were not blinded or even randomized.

There is a general consensus in psychiatry that SSRIs do not cause dependence, and have no abuse potential. For example, a careful study of post-marketing reports (open access at http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=8971432) by the experts from the UK government Committee on Safety of Medicines and Medicines Control Agency concluded: "They [withdrawal reactions] have been reported more often with paroxetine (0.3 reports per thousand prescriptions) than with sertraline and fluvoxamine (0.03), and least often with fluoxetine (0.002)." However, "there was no evidence of habituation or tendency to escalate the dose, and no other evidence of physical dependence." The Sceptical Chymist (talk) 00:38, 15 February 2009 (UTC)

The consensus is that antidepressants are not associated with the symptoms of psychological dependency/addiction such as dosage escalation, abuse and craving. There is a consensus that they can cause a dependence in terms of a withdrawal/discontinuation syndrome. That paper that I cited confirms that. I included in the data that I added that antidepressants are not associated with abuse. I think that the problem is what an author of a paper or review means by dependency. Some when saying no dependency are meaning little to no addiction/habituation (in terms of craving and dose escalation) and abuse. The no evidence of physical dependence I personally think is scientific fraud and the result of conflict of interest and lobbying and whatever. There is plenty of evidence in the peer reviewed literature of upregulation and down regulation of transmitter systems and receptor sites in animal studies and it undoubtly occurs in humans as well and is why you get physical withdrawal syndromes when discontinuing antidepressants. If there is no physical changes or adaptions in the CNS how else do you explain the withdrawal syndrome which can be severe and quite prolonged in some people from SSRIs scientifically?--Literaturegeek | T@1k? 00:55, 15 February 2009 (UTC)

Hmmm, do you really believe that 0.03% of people per thousand experience withdrawal syndromes from paroxetine? Here is what the CSM initially said about benzodiazepines in 1980. "The number dependent on the benzodiazepines in the UK from 1960 to 1977 has been estimated to be 28 persons." I thought you were the sceptical chemist. :=)--Literaturegeek | T@1k? 01:01, 15 February 2009 (UTC)

I have a feeling that I have opened up the can of worms which I try to avoid, which is the unwinnable debate of just what is dependence. Are dependence and addiction the same thing? I still think though the statement that antidepressants don't induce physical dependence to be scientific fraud but I admit that many review bodies have made this statement in their reviews and am aware of it. SSRIs like other non-GABAergic psychotropic drugs almost certainly don't induce a physical dependence to such a severe extent as GABAergic drugs such as alcohol, benzos, ether etc which science has well established produce some of the most profound physiological adaptions (physical dependence) of all psychotropic drugs.--Literaturegeek | T@1k? 01:09, 15 February 2009 (UTC)

I applaud your decision keep to the published facts as WP guidelines recommend. We may disagree with it, but the commonly accepted definition of physical dependence does include tolerance, which is not observed with paroxetine and other SSRIs. Even if we accept the conclusions of the article you quote, the fact that paroxetine was not mentioned in it makes it unsuitable for the Paroxetine article. Before starting this section, I wanted to find real examples of paroxetine dependence, so I ran a PubMed search on "paroxetine and dependence". The single relevant article out of 59 hits was the CSM study I quoted above, which argues against physical dependence. I would welcome any real citation indicating paroxetine dependence. Please remember that withdrawal syndrome, even severe, does not constitute dependence. Caffeine also gives a withdrawal syndrome (see Caffeine#Tolerance_and_withdrawal. Potentially lethal withdrawal syndrome can be caused by such uncontroversial drugs as propranolol, see [16] and prednisolone, see [17]. The Sceptical Chymist (talk) 01:44, 15 February 2009 (UTC)

Hmmm, true and physical adaptions is evidence of a degree of tolerance developing, but it may only be partial tolerance and therapeutic and pharmacological properties may still be retained on a constant dose (if partial tolerance and not full tolerance develops). A problem with that definition is an alcoholic never becomes "tolerant" to alcohol. They will always get drunk. Even if they drink the roughly the same amount say a litre of vodka per day, they will still notice its effects and get drunk/intoxicated on a litre of vodka. So by that definition one could argue that alcohol does not induce physical dependence. Opiates also generally don't lose their pain relieving properties completely and pain patients can be kept on a maintenance does with some analgesia, although partial tolerance may still occur. I think that SSRIs retain some of their therapeutic properties although i have heard from one psychologist who said that after 5 years SSRIs stop working. He also added most of the time they don't work but when they do work they work quite well but stop working after 5 years or so (due to tolerance? dunno annecdotal word of mouth research :)). Anyway so tolerance doesn't develop to alcohol's intoxicating effects or if it does it is at best slight to moderate, so can alcohol be categorised along with paroxetine as being a drug which doesn't induce physical dependence? Do you see what I mean by the unwinnable argument I started? :+-) I am not looking for an argument, I mean no harm.--Literaturegeek | T@1k? 01:53, 15 February 2009 (UTC)

Propranolol and prednisone I know can cause withdrawal type reactions if discontinued. Infact prednisone, modulates the GABA_A receptor much like barbiturates, benzodiazepines do, increasing chloride ion flow via modulation of the neurosteroid binding site. So prednisone probably invokes similar adaptions to alcohol, benzos and barbs, although I am not completely up to scratch on the effects of neurosteroids on the brain and not prednisone in particular. Maybe it modulates other sites in addition or more strongly so I could be wrong but am fairly sure.--Literaturegeek | T@1k? 02:02, 15 February 2009 (UTC)

No, the alcohol is not a good exmple. Drunkards drink amounts regularly, which could kill the naive person. This is even more the case with opiates. A naive person could swiftly be killed by the normal "maintenance" dose of an addict. 70.137.151.133 (talk) 02:07, 15 February 2009 (UTC)

Propranolol is a good example and has nothing to do with GABA or addiction 70.137.151.133 (talk) 02:07, 15 February 2009 (UTC)

In propranolol the guy just gets such cardiovascular effects that his heart explodes or he pops the cork. :) 70.137.151.133 (talk) 02:15, 15 February 2009 (UTC)

I guess my point is physiological adaptions (receptor upregulation, down regulation, desensisation etc) occur with almost any psychotropic drug, even proton pump inhibitors or nasal decongestants can cause withdrawal or rebound symptoms but these adaptions are made by the body for no other reason than to overcome (produce tolerance) the drugs effects. With many drugs this is only partial tolerance and therapeutic effect is only partially lost or in the case of alcohol intoxicating effects are only partially lost due to partial tolerance. So if a person cannot discontinue or has great difficulty discontinuing a drug that their body is physiological tolerant to and getting physiological withdrawal symptoms, it is not physical dependence because the tolerance is not complete? And the question returns what about alcohol? Why is it classed as a drug of physical dependence if tolerance is only partial?--Literaturegeek | T@1k? 02:18, 15 February 2009 (UTC)

Yea but people who are physically dependent on benzodiazepines or barbiturates say like anywhere from 100 mg of diazepam or up to 2000 mg of diazepam equivalent can walk about and appear sober but an alcoholic could not appear to be sober after drinking 1 or 1.5 litres of vodka but would be very drunk. A normal person would be comatosed on 2000 mg of diazepam or possibly be dead but certainly would be hospitalised, likely in ICU. There is a difference.--Literaturegeek | T@1k? 02:18, 15 February 2009 (UTC)

Anyway to end the discussion, I don't mind deleting the reference and data I added if you feel it is necessary. The article wasn't on paroxetine specifically anyway but as antidepressants as a class.--Literaturegeek | T@1k? 02:18, 15 February 2009 (UTC)

Paroxetine in children. Not better than placebo. Suicidality and side effects - worse than placebo.

According to the MHRA report (see Report of the CSM expert working group on the safety of selective serotonin reuptake inhibitor antidepressants, read here [18])

• p.45: "Efficacy [of paroxetine] in major depressive disorder. Efficacy was evaluated in three randomised, double-blind, placebo-controlled trials (one of which also had an imipramine arm) involving a total of 767 randomised patients aged seven to 18, treated for eight to 12 weeks. Of these 378 received paroxetine. Dose range of paroxetine was 10mg-50mg/day. Efficacy was not demonstrated."
• p.45: "General safety profile [of paroxetine in children]. Data from controlled clinical trials were available for 378 patients treated with paroxetine at doses of 10mg–50mg for 12 weeks. Of these, 263 completed eight to 12 weeks of treatment. No deaths occurred in the trials. There are no controlled data on long-term safety. Emotional lability, hostility, insomnia, tremor, dizziness and somnolence were reported more often by paroxetine-treated patients than by placebo-treated patients. Discontinuation due to adverse events occurred in 38 (10%) patients treated with paroxetine and in 15 (5%) of patients treated with placebo."
• p.58. In a cohort study conducted by GSK "Among children and adolescents, rates of suicidal behaviour were significantly higher in ... paroxetine users compared with other SSRI users (HR=1.6, 95%CI=1.2-2.1)."
• p.60. Conclusion: "Data on the safety and efficacy of paroxetine in MDD in children and adolescents under the age of 18 did not demonstrate efficacy in depressive illness in this age group, and showed an increase in the risk of harmful outcomes, including episodes of self-harm and potentially suicidal behaviour in the paroxetine group compared to placebo. The balance of risks and benefits in this population was negative."

The opinion that "the risk of inaction may be greater" was expressed in http://content.nejm.org/cgi/content/extract/351/16/1598 about a general issue of treatment with antidepressants, not specifically about treatment with paroxetine. In the light of the above data, this opinion does not apply to paroxetine. The Sceptical Chymist (talk) 02:23, 18 February 2009 (UTC)

Thanks for the link and the breakdown including page references. The problem with this study, is that it excludes patients at the highest risk of suicide, which are the ones most likely to respond positively to the drug. It then must resort to subjective measures such as suicidality. Although this study is not specifically on paroxetine, it includes a much broader population. http://www.cmaj.ca/cgi/content/abstract/178/8/1005

This paper is irrelevant. This is an ecological study on prescription of antidepressants in general - not on paroxetine.The Sceptical Chymist (talk) 00:11, 19 February 2009 (UTC)

If you look at the risk ratio for paroxetine in this study, they overlap 1, indicating that there was no significant increase in risk. The data just do not support the conclusion that paroxetine increases the risk of suicide. http://archpsyc.ama-assn.org/cgi/content/full/63/3/332?ijkey=4336f950cf7e456762f36d974baea9212b8e2657 —Preceding unsigned comment added by 161.150.2.55 (talk) 13:41, 18 February 2009 (UTC)

The study you are quoting showed 2.65-fold increase in suicidal tendencies for paroxetine for all indications with the 95% confidence interval from 1.00 to 7.02-fold increase. It is statistically significant in my book. The FDA review, on which this study is based also came to the same conclusion:(http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4065b1-10-TAB08-Hammads-Review.pdf): "Paxil, all indications (Fixed effect model), Suicide Behavior or Ideation [codes 1, 2, & 6], Risk ratio (95% CI) = 2.65 (1.00,7.02). Note that the signal is suggested in both the MDD and the non-MDD trials." The Sceptical Chymist (talk) 00:21, 19 February 2009 (UTC)

Additionally, SSRIs and Paroxetine are still recommended for treatment in adolescents with MDD. http://www.ncbi.nlm.nih.gov/pubmed/17974724?dopt=Abstract http://www.ncbi.nlm.nih.gov/pubmed/11437014 —Preceding unsigned comment added by 161.150.2.55 (talk) 14:07, 18 February 2009 (UTC)

You misrepresent the literature. PID 17974724 states :"Note that only fluoxetine has been approved by the FDA for use in children and adolescents with depression...Overall, fluoxetine has had the largest number of studies with positive results, whereas paroxetine has had the largest number of studies with negative results.34–37,39,42,43". PMID 11437014 is the only positive trial of paroxetine. When combined with other negative trials as in the FDA or MHRA analyses, the results are negative. That is why paroxetine was never approved for the use in minors.The Sceptical Chymist (talk) 00:46, 19 February 2009 (UTC)

If it includes 1, it is not statistically significant. Careful, your "book" sounds like original research.

You 161.150.2.55 say "The problem with this study is that it excludes patients at the highest risk of suicide, which are the ones most likely to respond positively to the drug." That is your own interpretation, which is called original research and is forbidden on Wikipedia, see WP:NOR. You are trying to delete the conclusions of the systematic and comprehensive review by the UK drug authority MHRA: Data on the safety and efficacy of paroxetine in MDD in children and adolescents under the age of 18 did not demonstrate efficacy in depressive illness in this age group, and showed an increase in the risk of harmful outcomes, including episodes of self-harm and potentially suicidal behaviour in the paroxetine group compared to placebo. The balance of risks and benefits in this population was negative. You are trying to replace it by your own OR and a broken quotation from an irrelevant editorial - "the risk of inaction may be greater". The Sceptical Chymist (talk) 00:05, 19 February 2009 (UTC)

When a journal such as the CMAJ publishes an eidotorial about a paper in that journal, it usually means that the paper is controversial or there was disagreement among the editors.

I agree Sceptical and they were using a statement from an article on the general use (risk of inaction in depression in kids) of antidepressants in children and not paroxetine itself but are using their original research to apply it to paroxetine.--Literaturegeek | T@1k? 00:35, 19 February 2009 (UTC)

The sample is not on paroxetine exclusively. Although it may not be recommended, it is up to the doctors discretion and paroxetine is widely prescribed among both adults and adolescents.d

Paroxetine - more completed suicides in adults

The recent insertion in the lead associates paroxetine "with fewer suicides in adults". The supporting reference http://ajp.psychiatryonline.org/cgi/content/abstract/164/7/1044, does not really support it. The reference is not about paroxetine at all, but about the "relationship between antidepressant treatment and suicide attempts in adult patients in the Veterans Administration health care system." Although the veterans prescribed antidepressants had fewer suicides, it is a fallacy to conclude from these data that paroxetine decreases suicides in adults.

To the contrary, according to the FDA analysis of the clinical trials of paroxetine, there was 0 completed suicides in placebo groups vs. 1 completed suicide in the paroxetine group. (see Clinical review: relationship between antidepressant drugs and suicidality in adults by Stone MB, Jones ML in the Overview for December 13 Meeting of Psychopharmacologic Drugs Advisory Committee (PDAC), p.42 available at http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4272b1-01-FDA.pdf)

According to the internal GSK data made public in the Glenmullen's report, in clinical trials worldwide there were 5 suicides on paroxetine vs. 0 suicides on placebo. (posted at the US Senate Committee on Finance website at http://finance.senate.gov/press/Gpress/2008/prg061208a.pdf) The Sceptical Chymist (talk) 04:05, 21 February 2009 (UTC)

That is not true. The vast majority of clinical trials of paroxetine show statistically significant reduction in adult suicide. The same is true for teens, but that evidence has not been published. There is an ethical restriction against including suicidal teens in these studies. Think about it, would you give a suicidal teen a sugar pill and tell him "let me know how this works? Paroxetine is one of the top 50 most widely perscribed drugs. I guess you know better than everyone else.—Preceding unsigned comment added by 24.15.179.168 (talk)

So, you are saying that both the FDA and GSK are lying? :) The Sceptical Chymist (talk) 00:20, 22 February 2009 (UTC)

In reply to the anonymous URL above ("Paroxetine is one of the top 50 most widely perscribed drugs."), the undeserved popularity of the drug is one of the reasons why it is so controversial. Vioxx was a huge seller despite causing serious cardiovascular problems. If you are going to claim that a "vast majority of clinical trials" show a particular outcome, please cite at least one; WP article contents are limited to published reliable sources. Likewise, I am restoring the linked quotes from the prescribing information (which Skinwalker had deleted as "original research and scare quotes"), because they are published (not original research) and reliably sourced. I try to assume good faith, but Skinwalker, please explain why you call published quotes from GSK's prescribing information "original research" and "trial attorney puffery," and why you think quotation marks are scary?TVC 15 (talk) 04:26, 22 February 2009 (UTC)

Paroxetine. Dangerous during pregnancy.

The theratogenic effect of some antidepressants is a relatively new finding. It appears in reviews since 2006. However, it is uncontroversial and well-established. The prevailing consensus is that paroxetine is likely to cause congenital malformations.

Review (PMID 16926304): "Some reports indicate that paroxetine is more commonly associated with neonatal withdrawal than other SSRIs. Recently, paroxetine was associated with a 1.82-fold (95% CI 1.17 to 2.82) increased risk of congenital malformations compared with other antidepressants...Paroxetine may cause adverse outcomes in the neonate when used during pregnancy and should be discontinued in women who are pregnant or trying to become pregnant."

Review (PMID 17381382): "Selective serotonin reuptake inhibitors (SSRIs) are not generally thought to be major teratogens. Some recent studies, however, have suggested that paroxetine may be associated with a small increase in risk of congenital abnormalities, particularly cardiac defects."

Review (PMID 17397101): "For paroxetine, recent data call for caution in prescribing such a drug in early pregnancy."

Review (PMID 17688379): "It is unlikely that any marked teratogenic effect occurs with the possible exception of an increased risk for cardiovascular defects after maternal use of clomipramine or paroxetine."

Review (PMID 17697910): "Based on the studies analyzed, first-trimester paroxetine exposure was associated with a significant increase in the risk for cardiac malformation (odds ratio [OR], 1.72; 95% CI, 1.22-2.42)...Based on the results of this metaanalysis, first-trimester exposure to paroxetine appears to be associated with a significant increase in the risk for cardiac malformation."

Review (PMID 18983224): "Recent data suggest that paroxetine treatment leads to increased rates of congenital malformations, although this evidence is not conclusive. Paroxetine and paroxetine CR are not indicated for use in the paediatric population and are categorised as Pregnancy Class D."

FDA/GSK prescribing information (http://us.gsk.com/products/assets/us_paxil.pdf): "Usage in Pregnancy: Teratogenic Effects: Epidemiological studies have shown that infants born to women who had first trimester paroxetine exposure had an increased risk of cardiovascular malformations, primarily ventricular and atrial septal defects (VSDs and ASDs). In general, septal defects range from those that are symptomatic and may require surgery to those that are asymptomatic and may resolve spontaneously. If a patient becomes pregnant while taking paroxetine, she should be advised of the potential harm to the fetus. Unless the benefits of paroxetine to the mother justify continuing treatment, consideration should be given to either discontinuing paroxetine therapy or switching to another antidepressant. For women who intend to become pregnant or are in their first trimester of pregnancy, paroxetine should only be initiated after consideration of the other available treatment options."

American College of Obstetricians and Gynecologists recommends (PMID 17138801) that "paroxetine use among pregnant women or women planning to become pregnant be avoided, if possible."

The only review that denies the teratogenic potential of paroxetine is [PMID 19254517], a non-systematic review, which did not conduct meta-analysis: "Given the inconsistency of the findings and limitations of the methodology of the published studies, the teratogenic potential of paroxetine that has been reported in some studies remains unproven."

The Sceptical Chymist (talk) 00:00, 19 March 2009 (UTC)

Thanks for review links, although "prevailing consensus is that paroxetine is likely to cause congenital malformations" is perhaps not quite what you meant as that implies (to me) a greater than 50% chance of problem. I agree the papers agree a relative increased risk, so perhaps you meant "prevailing consensus is that paroxetine is likely to cause an increased risk of congenital malformations" ? Risk of continuing treatment has to be weighed against risk of stopping and it is interesting that the papers have slightly different takes on this. I've done a little rephrasing, but I agree paroxetine would not be my ideal choice in pregnancy (but "Dangerous during pregnancy" implies risk to mother rather than a neonatal risk). David Ruben ^Talk 04:08, 19 March 2009 (UTC)

David, thank you for rephrasing! Indeed the paragraph now looks much better. And you are correct, I meant "increased risk of". The only thing I do not quite agree with you about is the Gentile review. You note in your comment that the review "states further studies need (ie observing outcomes in those so treated, not quite same as deliberately choosing to treat with this drug". In fact, the review advocates large controlled prospective studies of paroxetine in pregnancy, which means exactly deliberately choosing pregnant women to treat with this drug. Here is a quotation from the full text of the review conclusions: "Large, epidemiologic, prospective, controlled studies should be designed to include a control group of untreated women diagnosed with the same disorder as the mothers who accept taking paroxetine during pregnancy." Suggesting such a study is not only ethically questionable in the light of the numerous warnings, it is also disingenuous. Such a study is all but impossible to run because you will never be able to recruit a sufficient number of pregnant women to include into the paroxetine group. The women will read the consent form that lists the teratogenicity suspicions and the FDA recommendations to switch to another antidepressant—and they will choose to be in the control group.The Sceptical Chymist (talk) 09:58, 19 March 2009 (UTC)

Not being able see full article, I can't directly comment: but I wondered if a prospective study needs to involve starting someone de novo on a drug, as they might already be taking it and for a variety of reasons choose/unable to discontinue once they become pregnant, and only these select group of patients followed for outcomes. Hence akin to monitoring say smokers for effects on bladder cancer, which does not need any non-smoker to start and clearly will exclude those who sensibly discontinue. But perhaps I'm misundertanding prospective cohort study, or in this specific example of what the proposed study design was ? Anyway the intriguing thing, for me, is that my local psychiatric service seems to dislike use of citalopram in pregnancy vs fluoxetine, yet above papers suggest no/little cause concern between these two.David Ruben ^Talk 13:06, 19 March 2009 (UTC)

RE: controlled studies. You are correct, that is how it is usually done. Perhaps, that is what Gentile meant. What puts me off is the wording "mothers who accept taking paroxetine". Not "who accepted", or "who have been using". Regardless, such a study is not going to happen. How will they find enough pregnant women being treated with paroxetine? With paroxetine now generic, who is going to sponsor the study? With other, possibly safer, antidepressants, who needs to run a study with paroxetine? Gentile should know that, nevertheless he "suggests" further studies and that is disingenuous. The Sceptical Chymist (talk) 23:38, 19 March 2009 (UTC)

RE: citalopram vs. fluoxetine. There was a study that indicated that fluoxetine may result in a higher frequency of congenital heart malformations than even paroxetine. Then, there were other studies that did not find any signal for fluoxetine. I have not read anything bad about citalopram, though... This is just another example that prescribing habits are often not evidence-based. ;) The Sceptical Chymist (talk) 23:43, 19 March 2009 (UTC)

anxiety disorders vs. depression

I found one of the articles addressing the marketing history of paroxetine. It suggests paroxetine may be prescribed primarily for anxiety:

"In 1992, when Paxil hit the market, it faced a seemingly uphill battle to wrest customers from older SSRIs such as Prozac and Zoloft. The U.S. Food and Drug Administration had approved Paxil for the treatment of depression, like those drugs. But its manufacturer, SmithKline Beecham (because of a 2001 merger, now GlaxoSmithKline), was more interested in positioning Paxil as a remedy for anxiety disorders...

The company quickly secured permission to market Paxil for the treatment of panic disorder and obsessive-compulsive disorder. By mid-1995, Paxil had become the fastest-growing SSRI in the United States. In 1996, sales of the drug had climbed 54 percent to $291 million.

Impressive though those numbers may be, SmithKline was on the verge of a much bigger marketing coup: The company had been working to win approval from the U.S. Food and Drug Administration to market Paxil as a treatment for the first of a series of little-known mental health ills. In 1999, the FDA agreed to allow Paxil's prescription for the previously rare "social anxiety disorder."

SmithKline hired a New York public relations firm to raise awareness about the syndrome. According to the trade journal PR News, Cohn & Wolfe "developed a plan to educate reporters, consumers, and, in some cases, physicians, in an effort to encourage diagnosis and treatment."

The article continues:

SmithKline's so-called public-awareness campaigns were just one half of a coordinated strategy, though. In 1997, the FDA relaxed its rules on pharmaceutical advertising to let the pharmaceutical industry bypass healthcare providers to market its wares "direct-to-consumer" (DTC in marketing shorthand). In 1996, drug companies spent $595 million on advertising. Within a year, spending rose to $843 million. By 2000, the amount had shot up to nearly $2.5 billion.

Paxil was the first central-nervous-system drug to be advertised by name on television, according to Advertising Age. With such tag lines as "Your life is waiting" and "What if you were allergic to people?", the spots targeted 18-to-34-year-old professionals.

In the weeks following the attack on the World Trade Center, Glaxo positioned Paxil as the perfect antidote to post-9/11 anxiety. "Your worst fears," agonized one woman, seated at a kitchen table, "the what-ifs... I can't control it." "I'm always thinking something terrible is going to happen," another woman fretted. "It's like a tape in my mind," a third confessed. "It just goes over and over and over."

If paroxetine is prescribed primarily as an anxiolytic, then the depression studies seem less relevant. Mwalla and Skinwalker argued that depressed patients are at risk of suicide anyway, so suicidality among paroxetine patients might not be caused by the drug. However, anxiety patients are not usually considered a suicide risk, and suicidality is an extraordinarily serious side effect for an anxiolytic. Generic benzodiazepines can in rare instances cause death (e.g. Heath Ledger), but they may actually be safer (and less addictive) than the "not habit forming" paroxetine that made so much $$$ for GSK. Since the major (possibly only) selling point for paroxetine was being supposedly safer than older drugs, the previously concealed withdrawal syndrome seems one of the most important facts about paroxetine.TVC 15 (talk) 00:07, 23 March 2009 (UTC)

I'm afraid I don't understand your point. Are you trying to refocus this article towards discussing anti-anxiety applications of paroxetine? Or are you just on your "Paxil is evil, GSK has infiltrated Wikipedia" soapbox again? Skinwalker (talk) 00:17, 23 March 2009 (UTC)

Skinwalker, before you falsely accuse me of soapboxing, please explain why you call published quotes from GSK's prescribing information "original research" and "trial attorney puffery," and why you call quotation marks scary? My point in the comment above was as stated above, i.e. your defenses of paroxetine based on depression may be largely misplaced because paroxetine's market position seems primarily as an anxiolytic. As for whether paroxetine is intrinsically evil, we have already discussed that above, so please re-read what I said there instead of falsely attributing the opposite to me. As for whether GSK has infiltrated Wikipedia, I have said repeatedly that if you and the other pro-paroxetine users worked for GSK, you would respect its trademark instead of carelessly confusing generic paroxetine with brand name Paxil. However, some on this page have expressly argued for a pro-paroxetine bias, in order to avoid 'scaring' depressed patients away from the drug. As I have said all along, WP:NPOV calls for neutral presentation of facts (favorable and unfavorable), not deliberate bias in favor of someone's idea of the right medical decision for people they haven't even met.TVC 15 (talk) 00:55, 23 March 2009 (UTC)

To respond to your points one by one:

You'll need to provide diffs where I referred to such information as original research or puffery. I don't recall the context. Furthermore, you have a habit of using scare quotes to denigrate material that you disagree with. Please stop it. It's not neutral, and it conflicts with the Manual of Style.

As far as the anioxlytic vs. antidepressant angle goes, it's nonsense. Our sources largely discuss the antidepressant applications of paroxetine, so that is what the article will focus on. A non-scholarly article in an alternative weekly does not trump peer-reviewed sources.

(Ignoring the bit about paroxetine vs Paxil trademark issues, which is just way too offtopic).

As far as a pro-paroxetine bias goes, you're really off base here. The article currently says that paroxetine is not effective vs. placebo, causes a discontinuation syndrome, and may be a teratogen. Do you know why I don't complain about that? Because that's what peer-reviewed sources, written by medical professionals, say. Further piling on with scare quotes, crap sources from alternative newspapers, and endless talkpage soapboxing is unhelpful at best, and disruptive at worst. Skinwalker (talk) 01:21, 23 March 2009 (UTC)

Here are two of the diffs: [19] and [20]. I used quotation marks to indicate that the phrases were quoted from the linked source. Your replacement of common terms with the manufacturer's preferred terms is not neutral, so please stop that. Encyclopedias (including especially WP) are written for a general audience, and WP:RS does not limit sources to manufacturer-sponsored studies. As for your other accusations, including "crap sources," you need to tone down your language and provide some diffs.TVC 15 (talk) 02:10, 23 March 2009 (UTC)

Skinwalker and TVC 15, please, let's be civil! The truth lies, perhaps, somewhere in between your opposing points of view. Since both of your points are legitimate and fact-based, it should be possible to find a compromise, and/or include both of them into the article. The Sceptical Chymist (talk) 10:47, 23 March 2009 (UTC)