In this post , you can see an example of an American paxil (seroxat) withdrawal litigation gag order .. ( this is only one page of the gag order which is several pages long)
You would have to ask the question…
If a drug is safe, then why pay out and gag claims against it?…
Click on the Image above to see the gag order document
http://fiddaman.blogspot.com/2007/12/seroxorcist.html
GSK admit that Seroxat can double the risk of heart defects and other malformations in babies born to Mothers ingesting Seroxat during pregnancy. This has been well documented already and the FDA and MHRA have issued warnings recently about the risks to newborns and the unborn.
There is also much documentation and research about babies suffering withdrawal and other side effects from exposure to Seroxat. But this is still a relatively new issue and there hasn’t been a lot of coverage of these terrible tragedies or these issues in the mainstream media ( although there is a lot of info on the internet about it).. It is a sensitive issue, but I feel it is one that needs to be explored further…
Seroxat was also recently reclassified from a category C drug to a category D…
Which means it does “officially” pose a significant risk to the foetus…
But… In this post I am going to concentrate on some other interesting information relating to Seroxat in the womb , and what I am interested in also is; how do we relate the malformations in newborns to the affects on adult use of Seroxat?
Well, you will notice that from a Seroxat study from the EMC website , there is an interesting fact about Seroxat’s effects on pups (baby rats)…
There was increased pup mortality ( dead baby rats) and also delayed ossification (delayed development/fusion of bones) was observed in the pups..
You can see from the links that problems with Ossification has actually happened to babies born with Seroxat induced defects …
When the seams of the skull close prematurely ( they fail to fuse or ossify) it is called craniosynotosis
Could this development of craniosytosis possibly be related to the severe headaches and head pressure documented in Seroxat withdrawal cases in adults?
What is craniosynotosis?
Craniosynostosis is the term for a group of conditions in which a baby’s head develops abnormally because the seams between the bones close prematurely. This prevents the head from developing normally and may be associated with changes in the upper facial bones. Craniosynostosis can usually be recognized at birth, but for a very small number of children it does not become obvious until one year of age or older.
Why was this not noted and explored further? and why did GSK not draw attention to this? Why was this dismissed?
Reproduction toxicity studies in rats have shown that paroxetine affects male and female fertility. In rats, increased pup mortality and delayed ossification were observed. The latter effects were likely related to maternal toxicity and are not considered a direct effect on the foetus/neonate. So , how does this relate to adults? …
Well, considering the drugs affects on the foetus can be seen as an indication that Seroxat can damage the Skull, the internal organs and cause breathing problems in neonates…. surely similar effects could happen in adult use of Seroxat?
Another example of how we can relate the problems seroxat causes in babies , is the evidence of babies born with PPHN (Persistent pulmonary hypertension) from exposure to Seroxat in the womb. PPHN is a life-threatening condition that typically involves severe respiratory failure in a newborn infant and requires immediate treatment.
Would this explain the breathing problems which have been reported extensively by adults suffering Seroxat withdrawal affects?…
There has also been widespread reporting of Seroxat affecting male fertility…
This was also reported in rats ..
(See Links At Bottom Of Post)
Fertility
Animal studies in rats found impaired pregnancy rates at high concentrations. High doses over many weeks led to irreversible atrophic changes in the seminiferous tubules of male rats.
Why has more attention not been brought to Paroxetine’s effects on rats, babies, in the womb and its relation to how it affects adults… ?
http://www.medscape.com/viewarticle/450390_7
http://emc.medicines.org.uk/emc/industry/default.asp?page=displaydoc.asp&documentid=2057
http://seroxatkillsbabies.wordpress.com/
( Blog from mother who gave birth to a baby with a paxil induced heart defect)
In this post I am going to compare the differences and changes between the current (2006) Seroxat PIL ( Patient Information Leaflet) and the PIL from twelve years ago (1996)
There is an earlier one from 1991 ( But it is sensitive information apparantly and I cannot post about it)
So, I will focus mainly here on some key points from these two PIL’s. You will notice the differences between them and how the side effect profile of seroxat has increased massively in size in a decade, it is really quite remarkable. Just reading the sheer volume of “official” Seroxat side effects added to the 2006 PIL would make anyone feel depressed or anxious… ( not to mention dizzy and nauseous) (My comments will be in brackets in italics after each point)
What is “Seroxat”?
Everyone has a substance called Serotonin in their body. Low levels of Serotonin are thought to be a cause of Depression and other related conditions. This medicine works by bringing the levels of serotonin back to normal. ( Unproven pseudoscience nonsense )
Seroxat works by relieving symptoms of depression and any associated anxiety. It also treats obsessions , compulsions and panic attacks. These tablets are not addictive. Most people find that Seroxat does not affect their daily lives . ( Not Classed as Addictive, but does cause Dependence which is Addiction , and does cause withdrawal which is a criteria of physically addictive substances )
The usual dose to treat depression is 20mg a day but your doctor may tell you to take up to 50mg a day.
Some people find that if they suddenly stop taking these tablets they feel dizzy, shaky, sick, anxious, confused or have tingling sensations. They also may have difficulty sleeping, and have vivid dreams when they do sleep. But these symptoms are unusual and generally disappear after a few days. ( never proven to work over 20mg )If you stop taking your tablets too soon your symptoms may return. Remember you cannot become addicted to Seroxat.
( Symptoms such as withdrawal? You can become addicted to Seroxat )Does “Seroxat: cause side effects? Any medicine can cause unwanted effects, with Seroxat any side effects are usually mild and go away after a few weeks. The most likely side effect of seroxat is that you might feel slightly sick. When taking Seroxat some people may find they have an upset stomach, a rash, or dry mouth. They may sweat more than usual or feel drowsy but unable to sleep soundly. They may also lose their appetite or become constipated. Men may have difficluty having an erection and may find it difficult to ejaculate. All of these side effects will go away once you stop taking the tablets. ( some of these side effects are permanent)
Patients can occasionalyy feel dizzy, shaky or restless or they may feel faint when they stand up. Very rarely patients may feel fascial, body or muscle spasms or sudden mood changes. ( This is very common, NOT very rare )
Depression is a common illness. At any one time one in 20 people will be suffering from it.
The balance of chemicals in the brain is thought to affect the way we feel. Serotonin is one of these chemicals and also thought to be low in people who are depressed.
It is important that even when you feel better , you continue taking these tablets until your doctor tells you to stop. This will reduce the chance of your depression returning.
( GSK wanted you to take this stuff for a long time)Seroxat treats depression and anxiety disorders. Like all medicines it can have unwanted effects.
It is therfore impotant that you and your doctor weigh up the benefits of treatment against the possible unwanted affects, before starting treatment. ( the risks clearly outweigh the so called “benefits”)If you stop or miss a does you may get withdrawal affects
If you feel restless and like you cant sit or stand still tell your doctorPossible Side Effects
Likely to affect up to one in 100 people
Unusual bleeding or bruising
Other possible side effect during treatment
Likey to affect up to 1 and 10 people
Feeling Sick
Change in Sex drive and Sexual FunctionLikely to affect up to one in 10 people
Increases of cholestoral in the blood
Lack of appetite
Insomnia
Feeling Dizzy or Shaky ( tremors )
Feeling Agitated
Blurred Vision
Yawning, dry mouth
Weight Gain
Feeling Weak
SweatingLikely to affect up to 1 in 100 people
Bried increase or decrease in blood pressure
Lack of movements, Stiffness , shaking or abnormal movements in the mouth and tongue
Skin rashes
Feeling confused
Hallucinations
Uritary incontinenceLikely to affect up to one in every 1000 people
Abnormal production of breast mik in both men and women
A slow heartbeat
Effects on the liver showing up in blod tests of your liver function
Panic Attacks
Overactive thoughts and behaviours (mania)
Feeling detatched from yourself ( depersonalization)
Feeling anxious
Pain in the joints or musclesLikely to affect up to 1 in 10,000 people
Liver problems that make the skin or whites of the eyes go yellow
Fluid or water retention which may cause swelling of the arms and legs
Sensitivity to sunlight
Painful erection of the penis that wont go away
Unexpected bleeding .eg. Bleeding gums , blood in the urine or in vomit or the appearance of unexpected
bruises or borken blood vessels
Some patients have developed buzzing, whistling, ringing or other persistent noise in the ears (tinnitus) when they take seroxatSeroxat is a treatment for adults with depression and anxiety disorders. It is not fully understood how Seroxat and other SSRI’s work but they may help by increaing the level of serotonin in the brain.
Other medicines or psychotherapy can also treat depression or anxiety.
( Seroxat is a lobotomy in pill form)____________________________________________________________________
I am going to focus on adult suicidality from Seroxat in this post. It is clear from the information in the previous posts how GSK hoodwinked the regulators for a licence to treat adults with Seroxat from 1991 onwards. They tried desperately to push for a licence to treat children with Seroxat as this would have increased its marketing profile, but they failed miserably.Also we can see from the previous links, that Seroxat clearly posed a danger to children and in the end GSK failed to prove the benefits outweighed the risks. The questions I want to ask here though are concerned with Seroxat use in the adult populations. If Seroxat greatly increases the risk of suicide, aggression and hostility in children with depression and other disorders then why wouldn’t it be the same for adults? No Doctor, psychiatrist or expert has ever been able to explain to me why the effects of Seroxat would be any different between a child or adolescent or an adult taking the drug. Why does GSK maintain that Seroxat is safe for use in the adult populations? when even they themselves admit that it can cause severe and dangerous side effects in children?
Are we to believe GSK’s original Seroxat adult clinical trial data submitted to the regulators to be an accurate and true representation of Efficacy?
Or, considering their history ,should we put our trust in an independently funded study? Well, there was an independent study done on Seroxat in August 2005. It caused a Media Storm at the time because it demonstrated that Seroxat is linked with up to a 7 fold increase in suicide compared to a placebo (sugar pill)… That means you are seven times more likely to kill yourself if you take Seroxat … And they prescribe this drug for Depression! ..
The mind boggles….
From The Times
August 22, 2005
Top-selling drug linked to increased suicide risk
By Nigel Hawkes, Health Editor
ONE of Britain’s most widely prescribed antidepressants has been linked to a seven-fold increase in suicide attempts.
An analysis of trials for Seroxat involving more than 1,500 patients found seven suicide attempts among those taking the drug and only one among those taking a placebo. Suicidal thoughts were also commoner among those taking Seroxat (paroxetine), by a factor of three to one.
Almost 2.4 million prescriptions for the drug were issued in England last year.
The data was available even before Seroxat was first licensed in 1990, the Norwegian researchers found. The findings are likely to be seized on by lawyers attempting to win damages against the drug’s manufacturer, GlaxoSmithKline, in the US and in Britain. The mental health charity Mind said the results were “extremely worrying” and confirmed what it had been arguing for years.
“By ignoring what mental health service users themselves have said about the medication and its effects, the drugs regulators may well have caused lives to be lost,” said Sophie Corlett, policy director of the charity.
Campaigners, including Mind, say the drug should be withdrawn from sale, but GSK and the Medicines and Healthcare products Regulatory Agency (MHRA) have defended it, arguing that its benefits outweighed the risks.
However the MHRA has said that too many drugs of this class, SSRIs (selective serotonin re-uptake inhibitors), have been prescribed, and has warned that they should not be given to under-18s.
The MHRA also said that an increase in suicidal thoughts among users of Seroxat “cannot be ruled out.” The new study suggests that such an increase should have been apparent from the beginning.
Sales of paroxetine have fallen sharply in the UK in the past three years after concerns about it were highlighted by the media.
A team led by Ivar Aursnes of the University of Oslo looked at 16 studies in which paroxetine had been compared with placebo, including previously unpublished data.
The trials covered a total of 190 patient-years of use of the drug and the results were published in the journal BMC Medicine.
Ms Corlett of Mind said: “This study would seem to be an extremely worrying addition to growing evidence raising serious concerns over the safety of paroxetine.
“Mind’s own research has revealed that 50 per cent of the people who contacted us to report a reaction to Seroxat had experienced feelings of wanting to self-harm or commit suicide, and 58 per cent of these people said they had not experienced these feelings before they started taking Seroxat.”
GSK said: “We will review this study carefully. However, these conclusions in no way reflect the picture that has been built up about the benefits and risks of paroxetine in adults through an extensive clinical trials programme involving 24,000 patients.”
The MHRA said that while a modest increase in suicidal thoughts and self-harm could not be ruled out for those on SSRIs, there was insufficient evidence to conclude that there is any marked difference between different SSRIs, or between SSRIs and other antidepressants.
The Norwegian group concluded: “The increased suicidal activity seen in children and adolescents on certain antidepressant drugs may well be present in adults. The restrictions in the use of paroxetine in children and adolescents conveyed by regulatory agencies lately should include usage in adults.”
__________________________________________________________________________________________
Drug suicide risk fears renewed
The researchers looked at 1980s studies into Seroxat
Further concerns have been raised about potential suicidal side effects of a commonly used antidepressant.
The drug Seroxat (paroxetine) is already banned from use by adolescents because of an increased risk of suicidal thoughts.
In the journal BMC Medicine, University of Oslo scientists said existing studies indicated these warnings should be extended to adults.
GlaxoSmithKline, which makes the drug, said it had helped millions.
“By ignoring what mental health service users themselves have said about the medication and its effects, the drugs regulators may well have caused lives to be lost “
Sophie Corlett, Mind
Paroxetine is one in a class of drugs known as Selective Serotonin Re-uptake Inhibitors (SSRIs).
In 2003, around 19 million prescriptions for SSRIs were handed out in England for the treatment of depression and anxiety.
Concerns over suicidal side effects for those taking paroxetine were first raised by the BBC’s Panorama programme in 2002.
Last year the Medicines and Healthcare products Regulatory Agency’s (MHRA) Committee on Safety of Medicines concluded that a modest increase in the risk of suicidal thoughts and self-harm for SSRIs could not be ruled out, but the benefits for adults outweighed the risks.
Safety review
The Norwegian researchers, whose study was triggered by a journalist from the Norwegian Broadcasting Corporation working on a medical information programme, analysed the results of 16 trials involving the drug.
The studies were presented to drug regulatory agencies in 1989, prior to the drug being licensed for use by doctors in the early 1990s.
In each, patients had either been given paroxetine or a placebo (dummy pill).
The researchers carried out a statistical analysis of all the results, taking into account the length of time patients were on the drugs.
The studies included 916 patients on paroxetine and 550 patients on placebo.
There were no actual suicides in any of the studies. However, there were seven suicide attempts in the group on paroxetine, and only one in the placebo group.
Writing in BMC Medicine, the team led by Dr Ivar Aursnes, said: “Patients and doctors should be warned that the increased suicidal activity observed in children and adolescents taking certain antidepressant drugs may well be present also in adults.
“We also conclude that the recommendation of restrictions in the use of paroxetine in children and adolescents conveyed by regulatory agencies lately should include usage in adults.”
‘Confirmation’
A spokesman for GlaxoSmithKline: “We take the safety of all our medicines extremely seriously and will, of course, review this study carefully when it becomes available.”
He added: “At this stage, it’s not clear what method the researchers have used to arrive at these numbers or which clinical trials they have selected.
“However, we can say that these conclusions in no way reflect the picture that has been built up about the benefits and risks of paroxetine in adults through an extensive clinical trials programme involving 24,000 patients or through the use of this medicine in tens of millions of people around the world.”
An MHRA spokeswoman said it kept the safety of all SSRIs under close review and all new evidence was carefully reviewed and considered to see if new advice was needed.
Sophie Corlett, director of policy at the mental health charity Mind, said: “This study would seem to be an extremely worrying addition to growing evidence raising serious concerns over the safety of paroxetine.
“It confirms what Mind service users have long been telling us anecdotally.
“By ignoring what mental health service users themselves have said about the medication and its effects, the drugs regulators may well have caused lives to be lost.”
Margaret Edwards, of the mental health charity Sane, said: “Seventy per cent of those being treated with the new anti-depressants respond well, and the risks of suicide from untreated depression must be borne in mind in balancing the risks and benefits.”
______________________________________________
Note : All information is provided with a link to source ( you might have to copy and paste it into your web browser to access the original information)
As we can see from the previous links, where Seroxat came from, how it was marketed and how it was sold and how it was released for public consumption…
Also from link 6, we can see that Marty Keller, Sally Laden, James MacCafferty and Neal Ryan all played a part in Study 329 , Glaxo’s dubious and ultimately flawed Seroxat Child study…
The result of which meant that Seroxat/Paxil was pushed on children , many of whom harmed themselves and committed suicide because of its promotion…
In the UK however, We think that the most important players to focus on in order to try to understand the Seroxat Scandal and how it came into being are the MHRA…
The MHRA is the UK’s equivalent of the FDA in America…
The organisation itself is in charge of drug regulation…
The BBC’s Panorama have done 4 exposes on Seroxat and some of it has touched on the failure of the MHRA in regard to Seroxat …
Who are the Seroxat Players in the MHRA…?
Namely they are Alasdair Breckenridge and Ian hudson…
Ian Hudson and Sir Alasdair Breckenridge were both once high level employees of GSK and now work for the MHRA ( the UK equivalent of the FDA) ..
______________________________________________
http://209.85.129.104/search?q=cache:URk6cw9FglYJ:www.dh.gov.uk/prod_consum_dh/idcplg%3FIdcService%3DGET_FILE%26dID%3D4685%26Rendition%3DWeb+Breckenridge+GSK&hl=en&ct=clnk&cd=13&gl=ie
Alasdair Breckenridge : “We must not get hung up on safety but instead must focus on risk-benefit”
When asked by Panorama whether GSK had acted promptly in getting the information about Seroxat’s use in children to the regulator, the MHRA’s chairman, Sir Alasdair Breckenridge, says: “This is a matter which we are investigating at the present time.
http://www.telegraph.co.uk/money/main.jhtml?xml=/money/2004/10/03/ccgsk03.xml
______________________________
In a letter to Professor Sir Alistair Breckenridge in January, Dr John Patterson, the ABPI president, wrote: “We remain concerned at the lack of representation of the pharmaceutical industry at board level within the MHRA … As the only regulatory agency that is fully industry-funded, we believe it is essential that we have a say on a variety of issues, not least financial matters relating to fees and service levels.”
http://www.guardian.co.uk/uk_news/story/0,3604,1318946,00.html
______________________________
I would be obliged if you would bring our concerns to the government
regarding the MHRA, and in particular the recommendation that they should
not be as close to the pharmaceutical industry. Please do also ask the
government to explain why they continue to allow the MHRA to be funded by
industry rather than from general taxation. Clearly by allowing the MHRA to be
funded 100% by the pharmaceutical industry the government have allowed the
system of drug regulation to become corrupt!
Please read the following excerpt from a transcript of the Health Select
Committee Investigation of the Pharmaceutical Industry Influence where Dr
Ian Hudson Director of Licensing for the MHRA had been called to give
evidence but failed to appear:
Q783: John Austin – I also note that we do not have Dr Ian Hudson with us
this morning, although he was listed as one of the witnesses. Is there any
reason why not?
Professor Sir Alasdair Breckenridge: Yes, Dr Hudson is one of our delegates at
the CHMP, the Committee on Human Medical Products at the EMEA and he is
there today. He is fulfilling a different role for the agency down there
http://209.85.135.104/search?q=cache…&ct=clnk&cd=67
____________________________
Glaxo’s representative in court, Ian Hudson, who now works for the Medicines Control Agency in the UK, argued that the occasional suicide or killing by somebody on Paxil is not sufficient evidence that there is a problem with the drug, considering the millions who take it.
The chief executive of Mind, the mental health charity, last night resigned from a high profile review of modern antidepressant drugs, accusing the British medicines regulatory body of negligence.
Richard Brook had a unique position as a lay member of the expert working group on the class of antidepressants which includes Seroxat and Prozac.
His resignation came in protest at what he considered a cover-up by the regulators, after months of pressure on him not to reveal the review’s findings that Seroxat has for years been prescribed by doctors in an unsafe dose and that the regulators had the evidence in their possession for more than 10 years.
Mr Brook’s resignation sheds a rare light on the workings of the secretive drug regulation agency and its advisers, and will heighten public concern over their relationships with the pharmaceutical manufacturers.
http://society.guardian.co.uk/mental…168612,00.html
___________________________________
Dr Ian Hudson is a physician who has practiced as a paediatrician for a number of years. He was formerly a research fellow at the University of Glasgow. He joined SmithKline Beecham in 1989 where he held various appointments in clinical research and development. He joined the MCA (Medicines Control Agency) in January 2001 as Director of the Licensing Division. He is the CHMP (Committee for Human Medicinal Products) delegate for the UK.
________________________________________________________
So, on Monday 29 January, Panorama promises to reveal the secret trail of internal emails which show how GSK manipulated the results of Seroxat trials in children for its own commercial gain.
The documents also reveal how the company continued to deny safety problems with the drug despite three investigations by Panorama reporter Shelley Jofre.
Almost a year ago there was another leak of secret data, this time from Dr Peter Breggin.
Each and every time more damning information becomes public, we are asked to believe that Ian Hudson did not have full knowledge of ALL the trials and data that appertained to Seroxat. Hudson was Glaxo’s Worldwide Director of Safety and had, in his own words, “a significant involvement in Paroxetine” (Seroxat).
What adds insult to injury is that this is the same Ian Hudson who now heads up the drug licensing operations of the UK regulator, the MHRA.
This is also the same Ian Hudson who decided not to appear to be questioned by the House of Commons Health Select Committee - although several senior figures from the Medicines and Healthcare Products Regulatory Agency attended the session, the committee said that it would also have liked to have heard evidence from Ian Hudson. MPs wanted to question Dr Hudson about the company’s drug paroxetine (marketed as Seroxat in Britain and as Paxil in the United States).They were particularly interested in evidence concerning the safety and efficacy of the drug in people under the age of 18.
And so we come back to the subject of the new Panorama programme which shows how GSK manipulated the results of Seroxat trials in children for its own commercial gain…
I’d like someone to ask Dr Ian Hudson where he was and what he was doing when all this was going on at Glaxo - when he had “significant involvement in Paroxetine” (Seroxat) and he was Glaxo’s Worldwide Director of Safety.
Panorama, Monday 29 January 2007, BBC One 20.30.
http://seroxatsecrets.wordpress.com/…nd-ian-hudson/
_________________________________________________
Around the time of 1998, when GSK were pushing Seroxat for other “disorders” in their bid to steal the crown off Prozac , there was some other interesting stuff going on …
Mostly concerning a pediatric (child ) study , ‘The Infamous Study 329′ ..
Up until 1998 , Seroxat was not licenced for use in children (under 18’s ) , although it was at a doctors discretion and it could be prescribed “off label” to this age group…( and it often was)
But Glaxo desperately wanted to prove that Seroxat worked in this age group (Efficacy) , if they could get a licence to treat childhood disorders with Seroxat , it would increase sales. Their profits were already massive from Seroxat ,( over a billion by 1998 ) but GSK wanted to dominate the market and they stopped at nothing in their pursuit to make Seroxat/Paxil the number one psychotropic drug worldwide.
The only problem was , they were finding it difficult to prove that Seroxat worked for kids, in fact their studies were proving placebos ( sugar pills) to be more effective than Seroxat in under-18’s …
And most disturbing of all, there were indications from Glaxo’s own trials that Seroxat increased the risk of suicide and hostility in Under 18’s, but GSK carried on regardless…
In the link above, you can access documents relating to study 329 and study 377…
There have been many players in the Seroxat Scam ,One such player was The “Author” of Study 329, an academic psychiatrist called Martin Keller. In the business he is refered to as a “key opinion leader” ..
In other words, his psychiatric and academic voice or opinion is listened to and respected…
But, it seems that Mr Keller didn’t actually write Study 329, he said himself in an interview that he didn’t go through all the raw data… And it seems from interpreting these documents that the study could well have been “ghost written” … So who did Write Study 329? … Was it Glaxo? Was it Glaxo’s marketing team? …
These are excerpts from the Study 329 correspondence ( they were released to the public last year, before that, they were protected under a court order )
RE: PAXll ADOLESCENT DEPRESSION PAPER
Dear Jim:
I am pleased to enclose a small supply of reprints of the paroxetine-imipramine
adolescent depression paper that was recently pub I ished in Journal of the American
Academy of Child and Adolescent Psychiatry. GSK funded the purchase of the
reprints. A total of 300 went to Marty Keller, who is corresponding author on the
paper, and the balance is being sent to Zach Hawkins for distribution to the
Neuroscience sales force. Samples are also being sent to Rocco and Neil.
The paper looks excellent and demonstrates the commitment of GSK to the field of
psychiatry. Thank you for your support.
Sincerely,
~
Sally K. Laden, MS
Associate Editorial Director
February 6, 2001
Martin B. Keller, MD
Department of Psychiatry and Human Behavior
Brown University School of Medicine
345 Blackstone Blvd
Providence, RI 02906
Dear Dr Keller,
We are pleased to enclose all of the materials you will need to resubmit your manuscript
“Efficacy of Paroxetine in the Treatment of Adolescent Major Depression: A
Randomized, Controlled Trial” to the Journal of the American Academy of Child and
Adolescent Psychiatry.
Enclosed in this package are the following items:
•
(submit 1 to the
journal. keep 1 for your files),
• Four copies of the revised paper without the highlighting (submit 3 to the
journal, keep 1 for your files)
On behalf of Sally Laden, it has been a pleasure working with you on this project.
Please keep us apprised of the status of this paper at the journal. Thank you and please
do not hesitate to contact us if you have any questions or need additional assistance.
From : Zachary Hawkins
Paxil Product Management
cc: RVPs
TSMs
Significance of article
“Efficacy of Paroxetine in the Treatment of Adolescent Major
Depression: A Randomized, Controlled Trial”
Martin B. Keller, M.D.
J. AM.ACAD. CHILD ADOLESC. PSYCHIATRY2001
2001, July, Vol. 40:7: 762-772
This “cutting-edge,” landmark study is the first to compare
efficacy of an SSRI and a TCA with placebo in the treatmen1 of
major,depression in adolescents. Paxil demonstrates
REMARKABLE Efficacy and Safety in the treatment of
adolescent depression.
In conclusion, the findings of this study provide evidence of the
efficacy and safety of Paxil in the treatment of adolescent
depression. Here’s another example of GlaxoSmithKline’ s
commitment to Psychiatry by bringing forth “cutting l~dge”
scientific data. Paxil is truly a REMARKABLE product that
continues to demonstrate efftcacy, even in this understudied
population.
________________________________________________________
So…
GSK finally got what they wanted, an academic interpretation of a clinical trial advocating the use of Seroxat in children…
Only problem was…
Study 329 didn’t actually prove anything …
It was purely GSK marketing gloss…
On the other hand study 377, did prove something…
It proved that Seroxat was no more effective than a sugar pill for the treatment of adolescent/child depression …
Two Studies, Two Results, and a Debate Over a Drug
The two drug trials were known within SmithKline Beecham as Study 329 and Study 377.
Study 329 suggested that the company’s popular drug Paxil might help depressed adolescents. Study 377, completed not long afterward, indicated that Paxil provided no more benefit than a sugar pill in treating depressed young people.
But only the favorable study was widely publicized by Paxil’s maker. The company chose not to discuss publicly the trial with negative results, and those findings came to light only when an outside researcher on the study team decided to disclose them at a medical conference.
Federal regulators in this country are now scrambling to reassess the effectiveness and safety of antidepressants like Paxil, after British regulators touched off a controversy last year by asking drug companies for unpublished data from antidepressant trials. That data suggested that several antidepressants, including Paxil, might give rise to suicidal thoughts in some young users - a potential problem not revealed in any published studies.
Yesterday, the New York State attorney general, Eliot Spitzer, entered the fray by taking the unusual step of suing Paxil’s maker, which is now GlaxoSmithKline. Mr. Spitzer’s suit accuses the company of consumer fraud for not disclosing all of its Paxil data.
Officials of GlaxoSmithKline defend their record, saying they provided all the results of their Paxil clinical trials to the Food and Drug Administration, as required by law. But the stories of Study 329 and Study 377 provide a window into a far broader issue - the fact that the results of many human clinical trials of drugs are often never widely publicized and that, in some cases, doctors may never learn that the trials were even conducted.
These days, most drug trials are sponsored by pharmaceutical companies. And for more than a decade, a growing number of medical experts have been urging drug makers to release more trial data and to create uniform means of disclosing results through central registries, so that policy makers and doctors can easily learn the results. Those advocates argue that such central databases are necessary because drug companies, as well as medical journals and researchers, tend to spotlight only trials that show positive results
The fates of Study 329 and Study 377 appear to underscore that point. Both tests were conducted during the mid-1990’s at various hospitals and medical centers - Study 329 at facilities in the United States and Study 377 at test centers outside of this country, including Canada, Mexico, Europe, South Africa and the United Arab Emirates.
Study 329, with its potentially positive findings for Paxil, was completed first. Its results were presented beginning in 1998 at several meetings of medical professionals. Meanwhile, a report of the trial, which was led by Dr. Martin B. Keller, a department chairman at Brown University Medical School, was submitted to a medical journal for publication, a process that subjects a study to peer review by scientists not involved in the trial.
Dr. Keller declined to be interviewed for this article. But Dr. Neil Ryan, a professor at the University of Pittsburgh, who was also involved, said he believed that the study was rejected by some journals before The Journal of the Academy of Child and Adolescent Psychiatry accepted it for publication in 2001.
In the case of Study 377, the one with negative findings, there were no press releases or publications. And without the action of Dr. Milin and a Canadian colleague, Dr. Jovan Simeon, the study’s findings might have been seen only by regulators and a few researchers.
The writer of “clinical psychiatry a closer look” wrote a poignant artice about the the Study 329 shambles… Here are some excerpts …
Tuesday, January 30, 2007
Keller, Bad Science, and Seroxat/Paxil
I will focus on Dr. Martin Keller and some seriously poor science in this post. Panorama did an excellent job of profiling Keller’s role in helping to promote paroxetine (known as Paxil in the USA and Seroxat in the UK). Note this is a lengthy post and that the bold section headings should help you find your way.
Who is Martin Keller? He is chair of psychiatry at Brown University. According to his curriculum vita, he has over 300 scientific publications. People take his opinions seriously. He is what is known as a key opinion leader or thought leader in academia and by the drug industry. What does that mean? Well, on videotape (see the Panorama episode from 1-29-07), Keller said:
You’re respected for being an honorable person and therefore when you give an opinion about something, people tend to listen and say – These individuals gave their opinions; it’s worth considering.
Keller and Study 329: GlaxoSmithKline conducted a study, numbered 329, in which it examined the efficacy and safety of paroxetine versus placebo in the treatment of adolescent depression. Keller was the lead author on the article (J American Academy of Child and Adolescent Psychiatry, 2001, 762-772) which appeared regarding the results of this study.
Text of Article vs. the Actual Data: We’re going to now examine what the text of the article said versus what the data from the study said.
Article: Paroxetine is generally well-tolerated and effective for major depression in adolescents (p. 762).
Data on effectiveness: On the primary outcome variables (Hamilton Rating Scale for Depression [HAM-D] mean change and HAM-D final score What exactly were emotional lability and hostility? To quote James McCafferty, a GSK employee who helped work on Study 329, “the term emotional lability was catch all term for ‘suicidal ideation and gestures’. The hostility term captures behavioral problems, most related to parental and school confrontations.” According to Dr. David Healy, who certainly has much inside knowledge of raw data and company documents (background here), hostility counted for “homicidal acts, homicidal ideation and aggressive events.”
Suicidality is now lability and overt aggression is now hostility. Sounds much nicer that way.
Conveniently defining depression: On page 770 of the study report, the authors opined that “…our study demonstrates that treatment with paroxetine results in clinically relevant improvement in depression scores.” The only measures that showed an advantage for paroxetine were either based on some arbitrary cutoff (and the researchers could of course opt for whatever cutoff yielded the results they wanted) or were not actually valid measures of depression. The only measures that were significant were either a global measure of improvement, which paints an optimistic view of treatment outcome, or were cherry-picked single items from longer questionnaires.
Also, think about the following for a moment. A single question on any questionnaire or interview is obviously not going to broadly cover symptoms of depression. A single question cannot cover the many facets of depression. Implying that a single question on an interview which shows an advantage for paroxetine shows that paroxetine is superior in treating depression is utterly invalid. Such logic is akin to finding that a patient with the flu reports coughing less often on a medication compared to placebo, so the medication is then declared superior to placebo for managing flu despite the medication not working better on any of the many other symptoms that comprise influenza.
Whitewashing safety data: It gets even more bizarre. Remember those 10 people who had serious adverse psychiatric events while taking paroxetine? Well, the researchers concluded that none of the adverse psychiatric events were caused by paroxetine. Interestingly, the one person who became “labile” on placebo – that event was attributed to placebo. In this magical study, a drug cannot make you suicidal but a placebo can. In a later document, Keller and colleagues said that “acute psychosocial stressors, medication noncompliance, and/or untreated comorbid disorders were judged by the investigators to account for the adverse effects in all 10 patients.” This sounds to me as if the investigators had concluded beforehand that paroxetine is incapable of making participants worse and they just had to drum up some other explanation as to why these serious events were occurring. David Healy has also discussed this fallacious assumption that drugs cannot cause harm.
Did Keller Know the Study Data? I’ll paraphrase briefly from Panorama, which had a video of Keller discussing the study and his role in examining and analyzing its data. He said he had reviewed data analytic tables, but then he mentioned soon after that on some printouts there were “item numbers and variable numbers and they don’t even have words on them – I tend not to look at those. I do better with words than symbols. [emphasis mine].”
Ghosted: According to Panorama (and documents I’ve obtained), the paper was written by a ghostwriter. Keller’s response to the ghostwriter after he saw the paper? “You did a superb job with this. Thank you very much. It is excellent. Enclosed are some rather minor changes from me, Neal, and Mike. [emphasis mine].” And let’s remember that Keller apparently did not wish to bother with looking at numbers. It would also appear that he did not want to bother much with the words based upon those numbers.
Third Party Technique: This is a tried and true trick – get several leading academics to stamp their names on a study manuscript and suddenly it appears like the study was closely supervised in every aspect, from data collection to data analysis, to study writeup, by independent academics. Thus, it is not GlaxoSmithKline telling you that their product is great, it is “independent researchers” from such bastions of academia as Brown University, the University of Pittsburgh, and University of Texas Southwester Medical Center and the University of Texas Medical Branch at Galveston which are stamping approval of the product. More on this in future posts.
Keller’s Background… It is relatively well-known that Keller makes much money from his consulting and research arrangements with drug companies. In fact, several years ago, it was documented that Keller pulled in over $500,000 in a single year through these lucrative deals. When looking at how he stuck his name on a study he did not write, endorsing conclusions that were clearly far from the actual study data, can one seriously believe that Keller operated as an independent researcher? Can you believe that this is an isolated incident?
See, for example, Keller’s involvement in a study examining the effects of Risperdal (risperidone) for the treatment of depression. This study was presented a number of times, and he never appeared as an author of any of the presentations. Yet when the study was published, his name appeared as an author. The real kicker was that he allegedly helped to design the study, according to the published article. If he had played a major role in the study, he would have been acknowledged earlier (via being listed as a presentation author), so he apparently helped design the study after it was completed, which is obviously a major feat! The whole story is here. Why put his name on the paper? So that readers would believe more strongly in the study due to his big name status.
In addition, Keller wrote about how Effexor reduces episodes of depression in the long-term though he clearly misinterpreted the study’s findings. To be fair, many other researchers have made the same mistake in believing that SSRI’s reduce depression. To quote an earlier post:
In other words, because SSRIs and similar drugs (e.g., Effexor) have withdrawal symptoms that sometimes lead to depression, it looks like they are effective in preventing depression because people often get worse shortly after stopping their medication. The drug companies (Wyeth, in the case of Effexor) would like you to believe that this means antidepressants protect you from re-experiencing depression once you get better, that they are a good long-term treatment. A more accurate statement is that antidepressants protect you from their own substantial withdrawal symptoms until you stop taking them.
Again, Keller is way off from the study data.
Keller on Camera: Keller’s response to being asked about the increased suicidality among participants taking paroxetine in Study 329 was interesting:
None of these attempts led to suicide and very few of them led to hospitalization.
Well then I suppose a huge increase in suicidal thoughts and gestures is okay, then? This is the commentary of an “opinion leader” – if statements such as the above shape opinions among practicing psychiatrists, then we really are in trouble.
Next: Well, consider this post just the start regarding Paxil/Seroxat. The way the data were pimped by GSK merits more discussion as does more discussion of allegedly detached academics and their role in this debacle.
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So far , Through the links I have provided on this blog, we can see where Seroxat came from, How GSK unscrupulously hoodwinked it passed the regulators (MHRA and FDA) and obtained a market to promote what was originally classified as a “hypnotic” chemical as an “antidepressant” treatment… Seroxat was then released to an unsuspecting and trusting public in 1991 , I call this The first wave , because it seems that from this period until 1998 , GSK were testing the waters with Seroxat , gathering data on how it would perform …How much could they get away with?
But it was in 1998, (when Seroxat was relicenced )that GSK Stepped up a gear, GSK went on a marketing Blitz … A triumph of Marketing over Science.. With the help of devious sales tactics, In 1998 , GSK turned Seroxat into a blockbuster…
Here is how they went about it :
Seroxat : For Shyness
New pill to beat shyness
Sunday Mirror, Oct 4, 1998
A PILL to combat shyness is being launched this week and will be available on the NHS.
The drug, which could relieve the symptoms of up to three million chronically- shy people in Britain, is reported to improve the condition within a week in some cases.
Seroxat, which was originally licensed to treat depression, has now been given the go-ahead to fight shyness and “social phobias”.
The drug works by increasing the level of seratonin in the brain, and could cost the NHS up to pounds 700 million a year if all the country’s shy people took it.
Thursday, 23 July, 1998, 08:56 GMT 09:56 UK
Shy? Try taking a pill
Social wallflowers could be transformed into outgoing party animals with the help of a new drug.
SmithKline Beecham claims its anti-depression drug Seroxat, launched in the UK in 1992, has been shown in tests to cure ’social phobia’.
It has applied to the US Food and Drug Administration for a licence to use the drug, now prescribed for panic attacks, for people diagnosed as having acute shyness.
The media has climbed onto the Seroxat bandwagon, hailing it as the big new thing in social drugs after anti-impotence pill Viagra.
They say Seroxat will help shy people get to the point where they might need Viagra.
Serotonin
The drug boosts the level of serotonin in the brain - the hormone which controls people’s moods.
It is already a major success at treating depression and its sales have risen by 23% in the last year.
It now accounts for one quarter of US anti-depressant drug sales and it was the fastest selling anti-depressant drug in the UK in the mid-1990s. In 1996, UK sales grew by 50%.
But if it gets approval to be used to treat acute shyness, sales are likely to soar.
“It would be used for the sort of people who would have to run out of a crowded room. The underlying problem is usually extreme anxiety,” he said.
-SMITHKLINE BEECHAM: SmithKline Beecham’s Seroxat/ Paxil approved in UK to treat social anxiety disorder.
PHILADELPHIA, PA — Seroxat/Paxil (paroxetine HCl) has been approved for the treatment of social anxiety disorder in the United Kingdom, SmithKline Beecham announced today. It is the first selective serotonin re-uptake inhibitor (SSRI) to be approved for this severely debilitating and little known anxiety disorder. Seroxat/Paxil is currently under review for this indication throughout
Pill to melt shyness
Most people call it extreme shyness. According to some experts, up to eleven per cent of people in Ireland suffer from it. They prefer to call extreme shyness “social phobia” and they say that people who suffer from it experience unimaginable torment and isolation.
Now doctors believe Seroxat, a pill to counteract depression, can also help these social phobics or people who are, literally, painfully shy.
Now, new research in Britain which reveals that the anti-depressant drug Seroxat successfully treats the condition has brought the plight of social phobics into the public mind for the first time.
On 9th January 1998, in the face of mounting adverse reports from users and GPs, Seroxat was re-licensed for a wider range of symptoms including depression accompanied with anxiety, obsessive compulsive disorder and panic disorder. Off label prescription included pre-menstrual tension and irritable bowel syndrome. This wider remit increased sales dramatically and for the first time people who had never been depressed or suicidal were being prescribed Seroxat. Unbeknown to them, they were exposed to the additional risk of dependency syndrome and a raised risk of suicide. No longer could depression, suicidal thoughts and acts suffered by these people be attributed to a relapse of their depressive illness.
Revealed: secret plan to push’happy’ pills
Jamie Doward and Robin McKie
Sunday November 7, 2004
The Observer
Britain’s largest drug company drew up a secret plan to double sales of the controversial anti-depressant Seroxat by marketing it as a cure for a raft of less serious mental conditions,
The contents of the 250-page document have alarmed health campaigners who accuse the firm, GlaxoSmithKline (GSK), of putting profit before the therapeutic needs of patients by attempting to broaden the market for the drug which has been linked to a spate of suicides.
The internal report carries a section which outlines how GSK planned to double sales of ’selective serotonin reuptake inhibitors (SSRI)’ - the industry term for anti-depressants - by winning the marketing war against Seroxat’s chief rival, Prozac, manufacured by Eli Lilly.
Written in 1998 and subsequently updated in following years, the section is entitled: ‘Towards the second billion - all SSRIs are not the same’ and discusses strategies to see off the threat posed by Prozac.
‘What this document makes clear is that a number of different forms of anxiety were being targeted in a systematic way. The thrust was to move sales beyond the $1 billion to $2 billion mark by pushing it to people who were not clinically depressed,’ said Professor David Healy, a psycho-pharmacologist at Cardiff University, who has given evidence to the House of Commons Health Select Committee.
Richard Brook, chief executive of Mind, the mental health charity which submitted the document to the committee, told the MPs it was ‘all about developing new conditions for that drug and demolishing the arguments of other competitors about why their drug was not any good’.
In addition the document shows GSK made a great virtue of the fact that Seroxat had a relatively short ‘half-life’ compared with Prozac, an argument which has subsequently proven deeply controversial.
A half-life is the scientific term for how long it takes for the concentration of a drug to drop by 50 per cent in a patient’s bloodstream. The company suggested Seroxat’s short half-life meant patients could come on and off the drug easily, compared with those on Prozac, even to the extent that they could take ‘treatment holidays’. ‘There was an argument that a short half life was really good news,’ Brook said.
But five years later, Seroxat has withdrawal issues. It’s the short half life that causes the problems. The substances get into the body so quickly it causes some sort of dependency reaction. So one of the things the company was saying was a benefit was actually a problem.’
In its submission to the parliamentary committee Mind said the original trial data submitted to the UK regulators by GSK showed the claim was at best ‘naive and at worst seriously mislead ing’. It added that ‘the Seroxat file is highly illustrative of using marketing information as facts’.
Concerns about the addictive properties of Seroxat saw the government ban its prescription to people under the age of 18 last year. This followed a review which found children taking it were more likely to self-harm or commit suicide.
A spokesman for GSK said Seroxat could be marketed at new conditions only after stringent testing. ‘Medical authorities around the world have required that GSK study each condition separately in order to prove benefit in each condition specifically.’
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In 1998 , GSK also released a sales memo to their Paxil ( Seroxat ) selling team …
The memo speaks for itself…
For more GSK / Seroxat internal memos and documents see link :
http://abcnews.go.com/Health/story?id=311956&page=1
The previous link was in regard to the FDA approval of Seroxat … (Paxil in the US) in 1993
But… It was actually first Licensed in the UK in 1991 (which undoubtedly swayed and influenced the FDA’s decision to grant it a licence too)…(Seroxat was then re-licensed by the MHRA in 1998.. )
Seroxat was licensed in the UK on 11th December 1990 for the treatment of mild to moderate depression. By 1993, 78 Yellow Card notification reports of adverse withdrawal effects had been received by the Committee for the Safety of Medicines (CSM) and Medicines Control Agency (MCA)2. This exceeded the total number of adverse reaction reports received for all of the benzodiazepines combined even though the SSRI’s were represented as safer drugs. The CSM/MCA responded issuing a single paragraph statement in a newsletter to GPs reminding doctors of the need for gradual withdrawal. They failed to mention that often withdrawal symptoms were being mistaken for depression relapses, for which GPs were prescribing even higher doses of the drug.
Charles Medawar and others claim that the practice of describing suicidal thoughts and acts in vague nomenclature is one method that has been used to disguise adverse effects. For example, ‘suicide’ repeatedly being described as ‘emotional lability’ in published reports, has been passed unchallenged by the MHRA.
Panorama revealed that Prof. David Healey, a psychiatrist and researcher in Bangor University, had for many years been concerned that the so called ‘depressive relapses’ experienced by Seroxat users were in fact withdrawal symptoms. On perusing the data comprising the Seroxat healthy control studies Healey discovered that these participants, who had never suffered from depression or suicidal thoughts or acts, started to experience suicidal thoughts on taking the drug, along with a cluster of distinctive withdrawal symptoms including the now well known symptom of ‘electric zap’ sensations in the brain. Moreover, Prof. Healey reported his concern that results had not been published of a controlled experiment undertaken by GSK in which 85% of healthy volunteers suffered adverse effects and one committed suicide. Prof. Heay claimed that GSK knew that approx. 1 in 60 adults on Seroxat made a suicide attempt while the figure for placebo was 1 in 550. It would therefore appear that GSK were aware of the risks Seroxat posed prior to their licence application. The question remains ‘how could Seroxat have ever received the endorsement of the licensing authorities – the MCA (now MHRA) in the UK and the FDA’?
For more on the Seroxat UK licencing debacle .. ( see link )
All new patients or volunteers on SSRIs regardless of their mental condition, child or adult,
face a finite risk of drug induced suicide in excess of any risk of suicide that they had
before medication. GSK presented randomised clinical trial (RCT) results to the MCA for
Seroxat in 1990 in their UK licence application. This showed that Seroxat was 8 times more
likely to cause suicide or suicide attempts than placebo giving a rate of 236 suicides per
100K patients, zero for placebo. After some debate the application was withdrawn.
GSK then manipulated the results of the same trial, shifting suicides from Seroxat onto
placebo, and re-applied in 1991. The adjusted figures showed that placebo was now twice
as dangerous as Seroxat, giving a rate for Seroxat of 168 suicides/100K patients and an
incredible 361/100K for placebo. This affront to medical ethics, logic and common sense
did not dismay the MCA and on the basis of this data the MCA granted the lifetime UK
licence for Seroxat, which was never to be scientifically and critically reviewed
subsequently. This dangerous, inexplicable and incompetent approval in the UK
undoubtedly influenced the FDA to follow suit 2 years later when the Paxil licence was
granted.
Regulatory Complicity
In February 1990. the Teicher article raised concerns that the recently licensed fluoxetine might trigger suicidality in depressed patients. In fact, as the meta-analysis of the clinical trial literature on SSRIs mentioned above (appendix 1) and submitted to you indicates, as of 1988, there was a demonstrable doubling of the relative risk of a suicidal act on an SSRI in these trials compared to placebo, even though the data on zimelidine had not been reported in the published papers.
By October of 1990, FDA had decided the issue of suicide on antidepressants was as Martin Brecher of FDA put it: “not .. a real issue, but rather as a public relations problem” (Brecher 1990)(appendix 7). My question is whether CSM/MCA had made a similar decision.
This determination that the issue of suicide induction was a public relations rather than a substantive issue was made without holding a scientific advisory meeting. When FDA held an advisory meeting on the issue of antidepressants and suicide in September 1991, evidence on two other SSRIs, sertraline and paroxetine, already with FDA for close to two years, was withheld from the meeting. The suicide and suicidal act data on SSRIs or other antidepressants has never been shown to an FDA advisory panel and has not until this year been reviewed thoroughly by MHRA. Viewing the issue as a public relations matter has been a crucial misstep that I would argue has led both regulatory agencies down a path of twisting the science to fit their position.
Although data submitted to FDA and CSM/MCA showed that there was an increased rate of suicides on antidepressants compared with placebo, this simple but crucial finding was obscured and continues to be obscured by two sleights of hand. First the results were biased by the inclusion in the placebo group of “washout” or “run-in” suicidal acts that had occurred before patients were randomised, as outlined above for the sertraline data. This spuriously increased the placebo rate. A further biased elevation of the placebo rate occurred by including post-continuation suicidal acts under the heading of placebo. These were acts that occurred either after patients had completed the randomised phase of the trial, and were potentially in withdrawal, or were taken from selected trials that were not part of the original clinical regulatory trial portfolio. The effect of these manipulations is laid out schematically in figures 1 & 2.
Ok, so we know that Seroxat (chemical : paroxetine ) first emerged from the labs at Ferossan , and we know that B.I. (boehringer-ingelheim) originally filed paroxetine in the class of “hypnotics”..
So how did GSK get it passed by the drug Regulators as an anti-depressant?…
This is how…. (for the full transcript of Breggins Article , click on the text )
From 1980-1991, approximately 5000 patients were tested on Paxil during SKB’s clinical trials.Eighty-three (83) different Paxil trials were conducted.Various time periods were involved in the individual trials.Many patients were tested for only a month or 6 weeks.Some were tested longer, including approximately 400 who were in trials longer than a year.SKB pulled out all the stops to ensure the trials were successful.Only two (2) positive trials are required for FDA market approval.By any reasonable person’s perspective, Paxil’s track record in the clinical trials was poor.After a decade of juggling data in the 83 different trials, SKB was finally able to cite four (4) “positive” trials and three (3) “supportive” trials to justify Paxil’s approval.Dropouts in most trials were rampant.Most of the dropouts occurred because Paxil caused adverse experiences, and the victims wanted nothing more to do with the drug.
Paxil’s clinical trials were a statistical sham.Rather than deal with real numbers, SKB created a fraudulent measuring standard called “patient years” (or “patient exposure years”).The need for “patient years” became obvious in the 1980’s.It was obvious in the late 1980’s and into the 1990’s that Paxil clinical patients were attempting suicide and suffering “adverse experiences” at an alarmingly high rate.Moreover, as indicated above, hundreds of Paxil volunteers dropped out because they could not tolerate the drug.The dropout rate was 20%.Fifty-eight (5 
patients alone attempted suicide after they were given Paxil.Hundreds of additional Paxil patients suffered adverse experiences caused by the drug.In 1991, SKB “ran the numbers” and discovered the absolutely horrible Paxil record.The 58 attempted suicides out of the patient base constituted a suicide rate of 0.77% in real numbers.Under clinical standards, a rate of 1% is considered a “frequent” occurrence.On those numbers, Paxil patients approached a “frequent” suicide rate.This was a far greater suicide rate than “placebo” or the other active drug being tested on the patient population.To avoid a company disaster on the Paxil project, SKB had to change the rules, and shift to the “patient years” sham.
22.The “patient years” standard is a sham by anyone’s common sense.It works like this.Assume 366 patients are selected at random to test Paxil.Three hundred and sixty five (365) patients take Paxil and suffer horribly the first day–immediately quitting the test.These patients are called, not surprisingly, “losers.”The 366th patient, however, tolerates Paxil quite well, and even improves on the drug, staying in one or more trials for a full year.This patient is a “winner” by SKB standards.Like a champion race horse, this “winner” is entered in all the sweepstake trials for Paxil–and these trials are intentionally programmed to be long.Knowing they have a champion race horse, SKB racks up “points.”By anyone’s common sense standards, 365 failures out of 366 attempts would render the drug a dismal failure.But not so under “patient years.”Under patient years, the one Paxil patient who tolerated the drug for one year counts the same as the 365 patients who couldn’t tolerate the drug and dropped out the first day.The “score” in this example is “one patient year” for each side.Not surprisingly, the mathematicians who go along with this voodoo math are subordinate to the physicians and clinicians in the corporate chain of command, and the physicians at the top of the FDA chain of command.
.
In Paxil’s clinical trials, SKB ultimately achieved positive results–as it were–because of emphasis on “subjective” testing data.Objective data is very scientific.Subjective data is less scientific.The latter requires more stringent controls to be applied scientifically.Subjective data is subject to the biases, opinions, and prejudices of the person(s) collecting the data.SKB’s subjective data to justify Paxil’s approval was obtained both from physicians, principal investigators (”PI”) (most of whom were physicians) and from patients.The physicians and PI’s were compensated handsomely by SKB for their participation in the trials.On information and belief, plaintiffs allege these individuals were hired only after appropriate screening to ensure they were friendly to the drug industry and SKB.
.It was in mid 1992 that Dr. Laughren was directed by the FDA to be the staff point person for the October 5, 1992 Paxil committee hearing.Dr. Laughren had earlier concluded he would recommend Paxil’s approval.Dr. Laughren was also getting promoted and had only recently assumed the higher position.He was being assigned to take over the position occupied by the FDA official who had telephoned SKB on the PR nature of the Prozac problem.Dr. Laughren was taking over the higher position very late in the game insofar as Paxil’s application was concerned.The earlier incumbent–as described–had already taken a position favoring Paxil’s approval, and was not modest in voicing full support for SSRI’s.It would have been highly unusual for the FDA to place in that position an individual who would upset the apple cart and refute what his/her predecessor had committed to on the Paxil decision–and of course that didn’t happen.Dr. Laughren fell in line with his predecessor and validated all of his predecessor’s findings.In preparation for the upcoming October 5, 1992 committee proceedings, Dr. Laughren wished to be “hands on” before committee members.His wished to make it appear that the FDA staff was totally in command of their domain.Here, however, is where the FDA regulatory system breaks down–and was broken in this instance.It is where, essentially, the government bureaucrat depended on the “regulated” in order to look good in the job and get through a particular project–and that’s what happened here.Both players–FDA staff and SKB–recognized they were dependent on each other to look good before the committee.Like the telephone tipoff on the suicide issue, this was a poor environment for checks and balances, or fostering effective FDA regulation on behalf of public safety.For several weeks leading up to October 5, 1992, Dr. Laughren depended on SKB to get up to speed for his expected presentation before the committee.This was notwithstanding that FDA had been provided all of Paxil’s trial documentation as the clinical trials had progressed throughout the previous decade.As Dr. Laughren was preparing for the committee hearing, he made several urgent fax appeals to SKB headquarters to help him prepare his presentation.He was not modest.He asked numerous questions.He asked for numerous, individualized research scenarios.Some were provided immediately from SKB’s computer.Others had to be specially gathered by SKB and forwarded later.To facilitate Dr. Laughren’s support for their product, SKB promptly and fully complied with all of his requests.These SKB and FDA principals operated on a “first name” basis in their fax exchanges.SKB officials were so friendly with Dr. Laughren, they addressed him as “Tom” in front of the committee podium.
When the FDA committee convened in Rockville, Maryland, on October 5, 1992, the FDA staff made their presentation first.SKB’s presentation followed.Dr. Laughren’s presentation was lengthy, and essentially constituted the FDA staff’s position on Paxil.In his overview to the committee, Dr. Laughren addressed many Paxil issues.Knowing the six (6) voting members would be interested in the “withdrawal” issue, Dr. Laughren felt obligated to explain to the committee FDA’s understanding on the Yugoslavia trial.That was that the Paxil withdrawal issue was not formally studied during the tests.Laughren told the committee in regard to the Yugoslavia trial:”There was no systematic effort really to look at the withdrawal syndrome, but in looking at the patients coming off of…(Paxil)…in the clinical trials, there was no strong suggestion of a withdrawal syndrome.”That was strange language coming from a top FDA official commenting on clinical trials.Proper science and clinical analysis do not permit a “strong suggestion” of anything without scientifically imposed controls to justify such a conclusion.
.At that juncture, SKB’s plan for the committee was proceeding smoothly.The FDA was in their corner, and the FDA staff had told the committee exactly what SKB had hoped they would.Then in the afternoon it was SKB’s turn to address the committee.SKB was not content to rest on Dr. Laughren’s commentary regarding the Yugoslavia study.SKB boldly went to the next level.SKB asserted to the committee that SKB had studied “whether or not there is a discontinuation syndrome in patients who are abruptly discontinued from Paxil.”The SKB representative continued:”To end with a brief discussion of whether or not there is a clear withdrawal syndrome, we have pulled upon the …(Yugoslavia trial)…”Then, SKB made an outrageous and categorical falsehood.The SKB representative told the committee SKB in the Yugoslavia trial attempted to “systematically assess a discontinuation syndrome.”This statement was in direct contradiction of Dr. Laughren’s earlier statement in the day that “There was no systematic effort really to look at the withdrawal syndrome.”Having refuted the FDA representation that there were no “systematic” tests on Paxil withdrawal, SKB then further claimed the tests were successful in that regard.The SKB representative told the committee they examined the data on the Phase II placebo group and that “few numbers of patients experienced any adverse event after being randomized off…(Paxil)…into the placebo group and the percentages are certainly very small.”What SKB failed to add was that no “adverse events” were reported on the placebo group because the eighteen (1 placebo victims’ symptoms were reported by SKB to have been “relapse” symptoms.Given the high bar established by SKB for relapse, the 18 placebo victims constituted a staggeringly high 45% of the placebo group.Had a reasonable clinical standard for “relapse” been set, it is quite possible 75% or 90% an or even higher casualty rate would have been recorded.
.Then a most startling and telling exchange occurred before the committee.The SKB proclamation that “systematic” withdrawal testing had been accomplished in the Yugoslavia trial caught the FDA staff representative, Dr. Laughren, completely off guard.Hearing the SKB representative directly contradict him on “systematic” withdrawal testing, and further hearing that placebo patients suffered no adverse effects after being taken off Paxil, Dr. Laughren interrupted the SKB speaker.From his perspective sitting in the audience, Dr. Laughren understood there were “crossed signals” before the committee between the FDA staff and SKB, and that the discrepancy required immediate correction.Dr. Laughren additionally understood there was now a gap in the testimony.Dr. Laughren understood the placebo group’s statistics meant nothing without comparison to the Paxil group.He then yelled up to the podium to the SKB representative, and the following exchange occurred:
Laughren:”Unfortunately you did not contrast…(the placebo group)…with the rates…(of adverse experiences)…in the patients who continued on…(Paxil)…”
SKB:”Right.I know the point you are going to raise, that it really does not look that different…”
Laughren:”That was my impression.”
SKB:”…from what you saw in the…(Paxil)…group, and that is a well founded point.So we very much agree with your earlier conclusion that there is no clear withdrawal syndrome but this was our attempt to try and investigate it in somewhat of a controlled fashion.”
In effect, SKB had just pulled off a coup.SKB had successfully and deceitfully maneuvered Dr. Laughren into making the case before the committee that withdrawal tests were conducted, and they proved Paxil “clean” on the withdrawal issue.SKB got Dr. Laughren to do their heavy lifting before the committee on a subject the FDA official had no personal knowledge of.SKB simply stepped aside and put icing on the cake with a polite “we very much agree with…(Dr. Laughren’s)…earlier conclusion that there is no clear…(Paxil)…withdrawal syndrome.”
.SKB’s tactic to skirt the withdrawal issue at the committee hearing was thus successful.After representation to them that Paxil had been systematically tested for withdrawal and that the tests were successful, the committee voted to approve Paxil.
Where did Seroxat Come from ?..
Who created it?..
What can we learn from its origins?…
In the middle of the 70s, reports of a new breed of antidepressant began emerging from small laboratories in Scandinavia. It was found that certain drugs like reserpine, a popular tranquillizer and anti-hypertensive treatment that depleted serotonin levels had an interesting side effect: it produced depression-like symptoms.
At the Danish firm of Ferrosan, the head of research was a man called Jørgen Buus Lassen, who supported the theory that the specific enhancement of serotonin might lift a depressive mood. He tested about 100 compounds before deciding on one that became known as paroxetine. ‘We did all the clinical trials,’ he says today from his office in Glostrup, near Copenhagen, ‘and what created most excitement among our scientists was that in some trials we saw that some patients who had been totally hopeless on the existing drugs and not at all responsive to treatment, were gradually becoming better and better. Some who had been unable to work for several years and had been in and out of psychiatric hospitals gradually came into normal life again.’
Dr Jorgen Buus Lassen wrote the first scientific paper on paroxetine in 1975, in the paper he was frank about the drugs limitations.’It didn’t work with all patients,’ he remembers. ‘In most studies we could just show that we had about the same efficacy as the older tricyclic antidepressants. We didn’t see a better effect, but we saw fewer side effects [mainly nausea].’
Dr. Jørgen Buus Lassen (Danish) received his DVM from the Royal School of Veterinary and Agriculture Science in Copenhagen. Dr. Lassen is co-founder of NeuroSearch A/S and has been the President and CEO of NeuroSearch since May 1989. He has more than 25 years’ experience within neuropharmacology and has authored or co-authored more than 30 publications, including the first paper published with respect to Paroxetin (Paxil, Seroxat), an antidepressant. From 1980 to 1988, Dr. Lassen served as Managing Director of Ferrosan A/S` research and development division, where Dr. Lassen was responsible for the expansion of all pre-clinical and clinical activities. He is chairman of the boards of NsGene A/S and Gudme Raaschou Healthcare Invest A/S and member of the boards of Bavarian Nordic A/S, Neurosearch A/S and NicOx S.A. Board member of Pharmexa since 1997. Reference is made to Pharmexa’s address.
Dr Jorgen Buus Lassen is also connected with NeuroSearch, he is the President and CEO of Neurosearch
Which is affiliated with GSK…
NeuroSearch and GlaxoSmithKline form strategic RD alliance
19 December 2003 - Announcement
PDF version
NeuroSearch and GlaxoSmithKline (GSK) today announced a five-year research and development alliance. The alliance comprises a number of research programmes within ion channels and the treatment of diseases of the central nervous system (CNS) including depression, anxiety, and schizophrenia. The new alliance combines NeuroSearch’s innovative research and development, and strong technology platform with GSK’s research, development, and commercial strength.
The option agreement gives GSK access to new drug candidates from NeuroSearch’s research and development within the defined area. This includes the Phase II triple monoamine re-uptake inhibitor NS2359, the Endovion programme and several other research programmes. The existing collaboration with GSK in depression disorders is integrated in the new agreement.
President CEO Jørgen Buus Lassen of NeuroSearch says, I am pleased that we were able to conclude this important strategic alliance with GSK as our two companies have had a well-functioning and trustful partnership within depression research for three years. I have a strong expectation that this extended partnership will be a major success for both companies.
http://findarticles.com/p/articles/mi_hb033/is_200301/ai_hibm1G197351003
GlaxoSmithKline (www.gsk.com) and the Danish company NeuroSearch (www.neurosearch.com) will collaborate to discover and develop “triple-action” monoamine reuptake inhibitors to treat depression and other mood disorders. (Development Updates).(depression and other mood disorders)(Brief Article)
For more info on Ferossan , Buus Lassen and the Origins of Paroxetine and how it came to be unleashed on an unsuspecting public see link on Seroxat link 1 (hypnotic narcotic) .. A very informative post by Rob Robinson on Paxil Progress…
www.paxilprogress.org/forums/showthread.php?t=11984&highlight=paroxetine+hypnotic
