An internal, confidential SmithKline Beecham document about studies 329 and 377 was issued. Studies 329 and 377 tried to prove Seroxat/Paxil worked in children. In summary it said “… the data do not support a label claim for the treatment of Adolescent Depression… efficacy had not been demonstrated.” Specifically about Study 329 “…the study failed to demonstrate a statistically significant difference from placebo on the primary efficacy measures.”
In other words – it didn’t work.
About Study 377 we read “… failed demonstrate [sic] any separation of Seroxat/Paxil from placebo.”
In other words – it didn’t work.
A fuller manuscript of Study 329 being prepared for publication. This was written by Sally K Laden but was attributed to Marty Keller, Neil Ryan and colleagues. The conclusion reads “Paroxetine is a safe and effective treatment of major depressive disorder in the adolescent patient.”
Internally at least SmithKline Beecham seem to have understood what the data from Study 329 really said. In an email to PR company Cohn and Wolfe, SKB said: “Originally we planned to do extensive media relations surrounding this study  until we viewed the results. essentially the study did not really show Paxil was effective in treating adolescent depression, which is not something we want to publicize.” [see August 2001]
GlaxoSmithKline sued by Tim Tobin after this father-in-law Donald Schell killed himself, his wife and his grand daughter in Gillette, Wyoming, USA, after being on Paxil (Seroxat ) for only two days.“I felt that something had almost turned him into a monster and the Don that I knew wasn’t that type of person. The only thing that had changed was the medicine he was taking, the Paxil [the US brand name for Seroxat].” Tim Tobin, Panorama, BBC, 2002
Donald Schell had apparently been depressed for the previous ten years – but not suicidal. He had taken just two Paxil (Seroxat ) tablets in two days, before he killed his family. The jury found GlaxoSmithKline to be negligent and awarded more than $6mn (£3.8m) in compensation.
June 11 2001:
Thousands of people in the UK could be hooked on the anti-depressant drug Seroxat, without knowing it.
Dr David Healy, a UK expert in antidepressants, has said he has seen records of trials carried out by the manufacturers which showed healthy volunteers were suffering withdrawal symptoms after taking the drug for just a couple of weeks. Dr Healy was given access to GSK’s archives because he was an expert witness in the Schell case.
He said more than half of people on Seroxat may have “significant” withdrawal problems.
He said: “For most people who take the drug, one of the key points that will concern people is that Seroxat (paroxetine) could make you physically dependent.”
June 14 2001:
People can’t get hooked on Seroxat as they did on the older drugs such as Librium and Valium, claims GSK.
For over a decade, the company line has been swallowed, along with the pills. But a court case in Wyoming, USA, has changed all that. The jury decided Seroxat – Paxil in the USA – was to blame for Donald Schell killing his wife, daughter, baby granddaughter and then himself.
Enter Ian Hudson, witness for the defence and at the time of his deposition earlier in 2001, worldwide safety director for GSK. That’s Ian Hudson, now director of licensing at the Medicines Control Agency in the UK.
What did he have to say to the evidence of Mr Schell’s closest remaining family and three psychiatrists who all believed the tablets of Paxil/Seroxat Mr Schell took for just two days precipitated him into an unnatural and totally uncharacteristic murderous and suicidal frenzy? His position is that an individual case cannot tell you one way or the other – only randomised controlled trials will do.
But Dr David Healy says that randomised control trials are the wrong tool to establish whether serious side effects are occurring. The way to investigate what is happening is to carry out a challenge-rechallenge trial, where people are given the drug, taken off it and then put back on.
But GSK has not carried out that sort of study to establish whether or not Seroxat can make people agitated, suicidal, murderous or hooked. Nor has it carried out a randomised controlled trial. Here is a black hole. There is no proof that the drug does these things, says GSK, and because of that there is no reason to carry out trials that might decide it one way or the other.
Does Mr Hudson still take that view now he is at the MCA (to become MHRA), which watches over the safety of the British public? “If he takes the position with the MCA that he took at the trial, then none of us is safe with any drug in the UK at the moment,” says Dr Healy. How would Mr Hudson even be able to blame alcohol for making someone drunk?
So what does Mr Hudson think? As always, the MCA declines to answer detailed questions.
The MCA will have been supplied with all the healthy volunteer data before it granted the licence for Seroxat. It doesn’t seem to have been worried then, which makes one wonder who, exactly, was steering them as to what it meant.
July 10 2001:
People prescribed anti-depressant drugs like Prozac and Seroxat by their GP may be at increased risk of suicide soon after starting the medicine, the British pharmaceutical company GlaxoSmithKline has acknowledged.
GSK, in the wake of the verdict and a $6.4m compensation award against it over the suicide of Donald Schell in the US, after he killed his wife, daughter and granddaughter while on Seroxat – called Paxil in the US – has complied with a request from the medicines control agency in Britain to issue a warning to doctors and to patients with packets of the drug.
GSK insists the timing of the warning, which was issued two weeks ago, soon after the Schell verdict in Wyoming, was nothing to do with the litigation brought by Donald Schell’s remaining family members.
Dr David Healy, however, is far from satisfied with the warning that the MCA and the drug companies have agreed.
The warning reads: “The possibility of suicide is inherent in depression and may persist until significant therapeutic effect is achieved, and it is general clinical experience with all antidepressant therapies that the risk of suicide may increase in the early stages of recovery.”
“The person taking the drug is left thinking he or she has a problem, rather than that the pill caused them the problem,” said Dr Healy.
SmithKline Beecham Paxil Product Management was writing to all sales representatives selling paxil and telling them about Marty Keller’s “cutting edge, landmark study  which was the first to compare efficacy of an SSRI and a TCA with placebo in the treatment of major depression in adolescents. Paxil demonstrates REMARKABLE Efficacy and Safety in the treatment of adolescent depression.”
The Guardian reveals that Seroxat tops the league table for complaints of side-effects made by doctors to the government’s committee on the safety of medicines under the yellow card scheme. A total of 1,281 complaints were filed – more than the combined total for the rest of the top 20 most cited drugs.
The watchdog group Social Audit complained about the wording on the Seroxat patient information leaflet. It states that “these tablets are not addictive”, and that withdrawal problems “are not common and not a sign of addiction”.
October 13 2002:
The Head of European Clinical Psychiatry at the pharmaceutical company GlaxoSmithKline has denied that the drug Seroxat can lead to addiction. In an interview with Panorama, Dr Alastair Benbow said the drug was well tolerated and had been used all over the world for a decade. Dr Benbow also added: “As with all prescriptions medicines, Seroxat does have side effects, but these are clearly stated in the information that’s made available to doctors and to patients.”
October 13 2002:
One of the most widely used anti-depressants in the world can be addictive, it has been claimed. The claims – made on Panorama – come as the makers of Seroxat are attempting to have their drug licensed for use by children in America.
January 8 2003:
Experts are looking at the safety of widely used antidepressants including Prozac and Seroxat. The review will look at a range of options, including whether the drugs should be banned. The government review began after members of the public and doctors raised concerns that the drugs can be addictive, contrary to manufacturers’ claims – and increase the risk of suicide in some patients.
March 11 2003:
A coroner calls for an inquiry into the widely-prescribed anti-depressant drug Seroxat. Powys coroner Geraint Williams has written to the UK Health Secretary to ask for an urgent inquiry and for the drug to be withdrawn from use.
It follows the death of a man from Brecon who killed himself two weeks after being prescribed the drug for anxiety – the coroner recorded an open verdict on Tuesday.
May 11 2003:
Panorama sent hundreds of people a detailed questionnaire about their experiences on Seroxat and received 293 replies. These in-depth replies were then sent to Charles Medawar of the group Social Audit, and his co-author Dr Andrew Herxheimer who wrote an analytical report into the value of the e-mails.
This report has been published in the International Journal of Risk and Safety in Medicine. It concluded that “their collective weight was profound” and that the value of a large amount of data coming in at once may be greater than continuing to examine a slow trickle of reports.
May 11 2003:
The makers of the popular anti-depressant Seroxat have denied claims that their product is addictive and causes suicidal feelings. Speaking on BBC One’s Panorama programme, Dr Alastair Benbow, head of European clinical psychiatry at GlaxoSmithKline, admitted that people could have misunderstood the information on patient leaflets which said the drug was not addictive.
May 11 2003:
GSK, which makes the anti-depressant Seroxat is to drop the wording that it is “not addictive” on its patient leaflets. The move by the drugs giant follows complaints from viewers of BBC One’s Panorama programme, who complain of severe withdrawal symptoms and say they have been unable to stop taking the drug.
May 27 2003:
The government is launching a major inquiry into the safety of some of the most prescribed anti-depressants, including Seroxat. An expert group of the Committee on Safety of Medicines is to be set up to look at the problems some patients have reported while taking selective serotonin re-uptake inhibitors (SSRIs), which include Seroxat and Prozac.
And for the first time ever, the inquiry will take first hand reports from people who claim to have problems and investigate reports of suicidal behaviour.
June 9 2003:
Experts are set to update the safety advice provided with the controversial antidepressant Seroxat. The drug has been at the centre of a storm amid claims that it is addictive and could increase the risk of violent behaviour in some patients. Its maker, GlaxoSmithKline, insists that it is a safe drug – prescribed to thousands of patients in the UK.
June 10 2003:
Young people under the age of 18 should not be prescribed the controversial drug Seroxat, government advisors have ruled. It follows a review which found children taking the anti-depressant may be more likely to self-harm or partake in suicidal behaviour.
The Medicines and Healthcare products Regulatory Agency (MHRA) has also warned that adults who are on the drug should not suddenly stop taking it.
June 25 2003:
GSK quietly revise prescribing instructions for Seroxat. The company upwardly revises its 2002 estimate of the risk of withdrawal reactions – from 0.2% to 25%.
The official risk of Seroxat withdrawal problems had increased overnight from 1 in 500 to 1 in 4.
November 20 2003:
A system designed to highlight dangerous side-effects of medicines is not working, claim researchers. Doctors, and other health professionals are supposed to notify watchdogs if a patient reports an “adverse effect”. However, a researcher from the University of Oxford says that this information is wasted because it is not analysed properly.
February 3 2004:
Drugs giant GlaxoSmithKline knew that the anti-depressant Seroxat could not be proved to work on children in 1998, according to a leaked internal document.
The secret document, relating to two clinical trials held in the 1990s, reveals that drug trials had shown little or no effect on helping depression in minors.
The company was also advised to avoid publishing the full data because it would be “commercially unacceptable” and would “undermine the profile” of the drug.
The confidential paper, sent anonymously to BBC’s Panorama programme, reveals that the company were advised to publish only the positive aspects of one study and that there were no plans to publish a second – more negative – study.
In the USA, The FDA calls for label change for all major antidepressants urging doctors to closely watch both adults and young people for suicidal tendencies and increased depression.
March 11 2004:
Experts have warned doctors not to start patients on high doses of the antidepressant Seroxat. The Committee on Safety of Medicines says patients should initially be given a dose of 20mg a day.
March 13 2004:
The head of mental health charity Mind has resigned from a review of anti-depressants accusing a government drugs watchdog of negligence.
Richard Brook acted after GPs were advised to limit doses of the anti-depressant Seroxat. He claims the Medicines and Healthcare products Regulatory Agency (MHRA) knew about the concerns for 10 years and he was pressured not to reveal them.
June 2 2004:
UK drugs group Glaxosmithkline (GSK) has been sued in the US for allegedly lying about the effectiveness and safety of its antidepressant Paxil.
June 18 2004:
GlaxoSmithKline has announced plans to publish clinical trial results for some of its medicines on the internet.
In the USA, The FDA posts new analysis that shows evidence of a link between the drugs and suicidal thoughts or actions in young people.
August 27 2004:
GlaxoSmithKline has agreed to publish results of clinical tests on its drugs, to settle a US lawsuit.
GlaxoSmithKline (GSK) is facing a US lawsuit alleging that it covered up negative research findings on its anti-depressant drug Paxil.
The lawsuits were filed on behalf of children and teenagers who were prescribed Paxil, known as Seroxat in the UK and Europe.
October 15 2004:
The FDA, in the USA, orders that a “black box” warning be included on all antidepressants.
In the USA, ABC News uncovers internal documents that suggest GlaxoSmithKline, maker of the popular antidepressant Paxil, was aware that the drug had little or no effect in treating depression in children and adolescents, and that it may cause suicide-related behaviours in young patients. In spite of this information, GlaxoSmithKline distributed a memo to its sales force in 2001 touting the drug’s “remarkable efficacy and safety in the treatment of adolescent depression.”
February 18 2005:
Modern antidepressant drugs like Prozac and Seroxat may make patients twice as likely to try to kill themselves than if they were not taking any pills at all, according to a new study published today.
The British Medical Journal published three studies on SSRIs (selective serotonin reuptake inhibitors).Two of the studies look at reported suicides and suicide attempts in trials undertaken by the drug companies before applying for a licence.The larger of the two, by Dean Fergusson of the Ottawa Health Research Institute in Canada and colleagues, looked at data from 702 published trials which included 87,650 patients.
It found a twofold increase in the risk of a suicide attempt on the drugs. The increase is still small – 5.6 attempts per thousand patient years – but, they say, it is significant because of the widespread use of the drugs.
The authors say there may be a larger problem because they believe that some suicide attempts were not recorded.
March 5 2005:
The US authorities yesterday seized stocks of top-selling GlaxoSmithKline drug, Seroxat, because they were poorly made and posed a health risk to patients.
The seizures are a major blow as they will lead to shortages of drugs in America. The US regulator, the food and drug administration, found that tablets of the antidepressant Paxil, known as Seroxat in Britain, could split and might not contain any drug at all.
The regulator took action after Glaxo, Britain’s largest drugs firm, received consistent warnings about the poor quality of manufacturing at its plants in Puerto Rico.
March 22 2005:
The Select Health Committee publishes The Report of the Fourth Session 2004-05 entitled The Influence of the Pharmaceutical Industry.
From the MHRA, Professor Alaisdair Breckenridge (Chairman), Kent Woods (CEO) and June Raine (Director of Vigilence and Risk Management) are asked to attend a hearing for questioning in January 2005. Also from the MHRA, Ian Hudson is asked to attend but does not. Prior to joining the MHRA, Hudson was Worldwide Director of Safety at GlaxoSmithKline, with a significant involvement in Seroxat. During the hearing, angry MPs are unable to ask specific questions regarding the safety and trials of Seroxat due to Hudson’s non apperance.
Among its recommendations, the Report calls for more control over the way Pharmaceutical companies market their drugs, as well as calling for a complete review of the MHRA itself. The MHRA appoints a Director of Communications (Marketing and PR).
August 22 2005:
Commonly used modern antidepressants can cause adults as well as children to attempt suicide, a new study says.
An 18-month inquiry convened by the Medicines and Healthcare Regulatory Authority (MHRA) in the UK banned the use of the drugs, known as the SSRIs (selective serotonin reuptake inhibitors) in children and adolescents.
Last December it said the drugs were over-prescribed though they could safely be used by adults.
But a study published today in the online journal BMC Medicine casts doubt on the MHRA’s findings. One of the manufacturers, the British company GlaxoSmithKline, which makes the bestselling Seroxat, did not submit its original detailed data from clinical trials of the drug to the regulator, said the Norwegian author of the report, Ivar Aursnes. “I think the UK investigation could have been even more thoroughly done if they had looked through the primary data,” he said.
He had attempted to alert the MHRA to his findings, he said. “I have tried but they have not shown any interest.”
September 9 2005:
GPs give little support to millions of patients who would like to come off antidepressants because they cannot stand the side-effects, the mental health charity Mind said today.
It found doctors wrote 29m prescriptions for antidepressants and 17m for anti-anxiety and sleeping pills in England last year.
GPs were keen to hand out the drugs, but they were not able to tell when patients were ready to come off them – and not good at helping them do so, the charity said.
Most GPs were unable to predict when patients could come off drugs successfully. Indeed patients who weaned themselves off against doctors’ advice, or without telling the GP, were more likely to succeed (53%) than patients following doctors’ orders (44%).
The survey – based on interviews with more than 200 recent psychiatric drug users – found 70% had felt pressured to take the medication and 60% experienced problems coming off it. This rose to 68% among users of the SSRI group of antidepressants such as Seroxat.
September 28 2005:
Doctors were yesterday told to stop giving antidepressants to children and people under 18, because of the risks that the pills will make them feel suicidal.
The new NHS guidance marks a watershed in the treatment of children’s mental health.
February 27 2006:
A previously sealed product liability report against Glaxo SmithKline (GSK) is published. The medical expert report documents how the company systematically hid and manipulated data concerning Seroxat (Paxil) induced suicidality in depressed adults. The number of suicide attempts on the antidepressant Paxil was under-reported and the number of suicide attempts on placebo was inflated.
It further documents how GSK hid the incidence of Paxil-induced akathisia (agitation with hyperactivity) and stimulation. Akathisia and stimulation are risks factors for suicidality and violence. The product liability report also cites previously unreleased FDA correspondence critical of GSK’s marketing and advertising tactics in regard to Paxil. The entire product liability report is reproduced on http://www.breggin.com and is based on a three-day examination of GSK’s sealed files at the company’s headquarters.
Dr. Peter Breggin’s original psychiatric expert report was written for Lacuzong v. GSK and signed as an affidavit in California on July 21, 2001.
The Lacuzong case was brought by the widow of a man who drowned their two children and himself in a tub after taking Paxil for three days. The Lacuzong case was “resolved” to the satisfaction of the family. At GSK’s insistence, Dr. Breggin’s report remained sealed. However, in a more recent case against the company, Moffett v. Glaxo SmithKline, the United States District Court for the South District of Mississippi, the report was filed in the public record.
April 10 2006:
In an email to anti Seroxat campaigner, Robert Fiddaman, Prof. Kent Woods, CEO of the MHRA, stands by Report of the Committee on Safety of Medicines Expert Working Group on the Safety of Selective Serotonin Reuptake Inhibitor Antidepressants, stating that “I have already given you a full account of the Agency’s position in this matter and there is nothing to add to it.”
This, despite recent new evidence suggesting that the Expert Working Group did not have access to all the clinical trial data as recently published in Dr Peter Breggin’s report.
GlaxoSmithKline (GSK) submits documents to the FDA in the USA and other regulatory agencies worldwide, contradicting its decade long denial that its antidepressant drug, paroxetine (Paxil/Seroxat) increased the risk of suicidal behaviour in the company’s controlled clinical trials. GSK insists the timing of the warning, made so soon after Dr. Peter Breggin’s previously sealed product liability report against Glaxo SmithKline was made public, has nothing to do with that document.
In a letter to healthcare professionals, GSK warns about the increased suicide risk stating: “There is a possibility of an increased risk of suicide related behaviour in young adults ages 18-29” – whether the drug is prescribed for depression or for other conditions not associated with suicide.
GSK is the first of the SSRI drug manufacturers to acknowledge in the Paxil label that the drug may trigger more than “suicidal thoughts.” – the drug increases the risk of “suicide attempts.” The Paxil CR label now includes the following warning “young adults, are at an increased risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment.”
GSK added warnings acknowledging that patients on the drug may experience “persistently worse” depression, or may “experience emergent suicidality or symptoms that might be precursors to worsening depression or suicidality” and “these symptoms” may be “severe, abrupt in onset, or were not part of the patient’s presenting symptoms.”
GSK advises doctors: “Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication.”
June 21 2006:
Petition presented to the House of Commons by Stewart Hosie MP: “I take enormous pleasure in presenting a petition on behalf of my constituent, Mr. D. Scott, from Dundee, who calls for the precautionary principle to apply to the prescription of Seroxat. He points out that many people who are prescribed Seroxat believe that they suffer side-effects, including aggression, fatigue, agitation and suicidal thoughts. Others suffer severe effects on withdrawal. He observes that a large amount of information on those side-effects is in the public domain, and he demonstrates the requirement for immediate action, including a moratorium on the prescribing of Seroxat to new patients”.
Declares that there is deep concern about the side effects that many people believe that they have suffered from being prescribed the drug Seroxat.
Further declares that the Health Select Committee should carry out an investigation into the drug and its possible side effects.
The Petitioners therefore request that the House of Commons urge Her Majesty’s Government to place a moratorium on the prescription of Seroxat to new patients until a review has been carried out on the large body of evidence which now exists concerning the side effects of this drug.
To lie upon the Table.
September 12 2006:
Study links violence with antidepressants.
The antidepressant drugs known as SSRIs, which include the British best-seller Seroxat, may precipitate a small number of individuals into violence, according to a paper published today on the Public Library of Science: Medicine website.
David Healy of Cardiff University, David Menkes of the University of Auckland and Andrew Herxheimer of the Cochrane Centre reviewed data from several sources including Seroxat’s manufacturer, GlaxoSmithKline. “The new issues highlighted by these cases need urgent examination in all countries where antidepressants are widely used,” they write.
January 29 2007:
GlaxoSmithKline, the UK’s biggest pharmaceutical firm, yesterday labelled as “defamatory” allegations in a Panorama programme that it had distorted trial results for Seroxat, its best-selling antidepressant.
An official at the company said it had looked into taking legal action, “but that there wouldn’t be much to gain from taking action against the BBC”.
The programme alleged that the company privately questioned the safety and efficacy of Seroxat among children under 18, but nevertheless promoted the drug to doctors for use in that age category. Karen Barth Menzies, the lawyer leading a US class action against GSK on behalf of families whose children committed suicide when using Seroxat, said: “They didn’t tell the regulators or the physicians or parents about these risks or the lack of efficacy. Instead they went out and promoted this specific study as remarkably effective and safe for kids.”
Panorama alleged that ghostwriters employed by the drug group influenced the independent academics who wrote the articles. The company admitted it used a medical writer from an agency, but maintained the ultimate responsibility lay with the independent authors of the article.
The Medicines and Healthcare Products Regulatory Agency (MHRA) began a criminal investigation in October 2003 to ascertain whether GSK withheld important information on the drug’s effect on children.
The agency has not yet finished its inquiry. The use of Seroxat in under-18s has been banned by the agency.
David Healy, a professor of psychiatry at Cardiff University, said: “During the course of the last five years, the pharmaceuticals industry has gone from being very highly regarded to looking little better than the tobacco industry.” He added: “People need to know that the statements the industry puts out there are open and honest. There needs to be a competent and independent person that goes in and has a look at what the data shows.”
The first Seroxat withdrawal action is started in the High Court in London.
Diane Smith claims she became agoraphobic when she tried to wean herself off the controversial drug. She even missed her son’s wedding and could not go to see her dying father as she has become a prisoner in her own home.
Diane, 43, of Thurso, Caithness, has issued a writ in the High Court in London claiming £50,000. Seroxat has been linked to a string of suicides and users say they have suffered serious side effects, including depression.
Diane’s case is the first to be lodged over the effects of coming off the drug.
Her action was launched this year to beat an English High Court 10-year timebar as she started taking the drug in 1997. Mum-of-four Diane was on the antidepressant for five years from August 1997 to June 2001.
She said: “I was walking on the beach with my handicapped son Lee, who is now 18, when I suddenly felt dizzy and the whole beach started to sway. It was the strangest sensation. “I went to see the doctor who said I was suffering from stress and prescribed Seroxat. I was on it for five years until 2001 when suddenly the psychiatrist took me off it. Then the trouble started. I felt suicidal. I get panic attacks and I cannot go out. I can’t even go to the supermarket just down the road. I’m a prisoner in my own home. When my son James got married I couldn’t go. When my daughter Denise graduated I couldn’t go and when my dad died I could not be at his bedside – all because of this drug.
I’m not really interested in the money. I’m more interested in getting the truth known because this drug is a danger.”
Her husband James, 50, said: “It’s been a terrible time for Diane and it has not been easy for the rest of us. It’s broken our hearts.”
Since it was first prescribed in 1990, Seroxat has been linked to at least 50 suicides of adults and children.
3 October 2007:
The MHRA ‘criminal’ investigation into GlaxoSmithKline is four years old this week.
It was four long years ago in October 2003 that the MHRA started a criminal investigation into GlaxoSmithKline because of concerns that Britain’s biggest pharmaceutical group had withheld important data from clinical trials. This data showed that Seroxat could cause an increased risk of suicide and self-harm if prescribed to depressed teenagers.
In January 2006, the MHRA told Panorama, “that the investigation has been given substantial additional resources and remains a high priority.” But the reality is that any prosecution of Glaxo would put the MHRA itself – and Chairman Alasdair Breckenridge in particular – too squarely in the frame.
17 November 2007:
First news breaks of the UK group action against Glaxo:
Pharmaceutical giant GlaxoSmithKline is facing a £30million damages claim from users of its anti-depressant Seroxat.Lawyers representing patients who insist the bestselling drug is addictive have issued the first of 600 High Court writs against the company, each seeking compensation of up to £50,000.
Since first prescribed in Britain in 1990, Seroxat has been linked to at least 50 suicides of adults and children.GSK, which makes up to £1billion a year from the drug, is already embroiled in lawsuits with American users, and has been accused of failing to act on warnings that it could have serious side-effects, including mood swings and personality changes.
Mark Harvey, of law firm Hugh James, claims Seroxat is “defective” under the 1987 Consumer Protection Act.He said: “When patients took the drug, not only was there no warning of withdrawal problems, there was also a statement on the data sheet until about 2003 which said you cannot be addicted to Seroxat.
“Unfortunately many people are having difficulties as they try to withdraw from the drug, and there are a few who have not been able to stop taking it.” Earlier this year the BBC’s Panorama programme alleged that GSK had covered up fears about Seroxat’s safety, which the firm strongly denied.
5 February 2007:
WARNINGS of the dangers of suicidal thoughts and behaviour are to be included in the packages of anti-depressants in the UK. Warnings will be carried in the patient information leaflet in the packets from October 2008.
The direction was issued 5 February by the UK Government’s Medicines and Healthcare Products Regulatory Agency (MHRA). A notice has been sent to drug manufacturers.
25 February 2007:
Kirsch study published.
One of the largest studies of modern antidepressant drugs has found that they have no clinically significant effect. In other words, they don’t work.
In the study, researchers conducted a meta-analysis of all 47 clinical trials, published and unpublished, submitted to the Food and Drug Administration in the US, made in support of licensing applications for six of the best known antidepressant drugs, including Prozac, Seroxat – which is made by GlaxoSmithKline – and Efexor made by Wyeth. The results showed the drugs were effective only in a very small group of the most extremely depressed.
Professor Irving Kirsch of the University of Hull, who led the study published in the online journal Public Library of Science (PLoS) Medicine , said the data submitted to the FDA would also have been submitted to the licensing authorities in Britain and Europe. It showed the drugs produced a “very small” improvement compared with placebo of two points on the 51-point Hamilton depression scale.
Tim Kendall, deputy director of the Royal College of Psychiatrists’ research unit, said the findings, if proved true, would not be surprising. As head of the National Collaborating Centre for Nice guidelines on mental health, he said it had proved impossible to get access to unpublished trials in the past.
“The companies have this data but they will not release it. When we were drawing up the guidelines on prescribing antidepressants to children [in 2004] we wrote to all the companies asking for it but they said no. The Government pledged in its manifesto to compel the drug companies to give access to their data but that commitment has not been met.”
March 6 2008:
The MHRA announces the result of its criminal investigation into Glaxo…
After a four-year investigation and examining 1 million pages of evidence, the UK’s Medicines and Healthcare products Regulatory Agency has decided not to pursue criminal charges against the drugmaker, although the agency did chastise Glaxo for failing to release more quickly clinical trial data about suicidal risk in youngsters.
The prospect of obtaining a criminal conviction wasn’t “realistic,” because the legislation in force in 2003 – when the investigation began – wasn’t clear enough, especially concerning the disclosure of data and off-label use, the MHRA said in a statement. Glaxo and individual Glaxo employees declined “invitations to attend interviews,” the MHRA says, but did provide three written witness statements – two on behalf of the drugmaker and one on behalf of an unnamed employee.
Glaxo provided the MHRA with data from clinical trials confirming that patients under 18 had a higher risk of suicidal behaviour if they were treated with Seroxat/Paxil, than if they received a placebo; and that Seroxat was ineffective in treating depression in kids.
Kent Woods at the MHRA wrote to JP Garnier:
Dear Dr Garnier
I am writing to advise you that the Medicines and Healthcare products Regulatory Agency is today announcing the conclusion and outcome of its investigation into a number of allegations regarding GSK, in particular that the company withheld from the MHRA important clinical trial data relating to the safety and efficacy of Seroxat in children and adolescents, and promoted that product for use in this age group despite safety and efficacy concerns.
In immediate practical terms, the outcome of the investigation is that, having considered our investigation report, government lawyers have decided not to pursue a prosecution of GSK. Their view is that the law at the time these events took place did not require a pharmaceutical company to inform the regulator of clinical trials date in groups for whom the medicine was not licensed, and that there is insufficient evidence of GSK promoting the product for “off-label” use in under 18s. We will today be issuing a press release to confirm that, and will be publishing on our website a short report setting out the conduct and conclusions of the investigation. I am attaching both the press release and the report for your records.
This is the immediate practical outcome but there are a number of other issues arising from the process. There is obviously a need to tighten the law to make it absolutely clear that pharmaceutical companies have a legal responsibility to inform the regulator of any information that changes the benefit risk profile of their products, regardless of whether the information relates to a licensed indication. We will be using the current European Commission consultation on pharmacovigilance regulations and other opportunities to press for changes to the law in this area.
Such a course of action should be unnecessary in an industry which relies so heavily on public trust and aspires to high ethical standards. I would have thought it self-evident that such information should be made available promptly to the regulator in order that action can be taken to protect public health. However, that moral responsibility now needs to be insisted up by the unambiguous force of law.
You will be aware that we have reviewed a large quantity of documents from GSK. Legal provisions prevent us from releasing publicly any information gained under our statutory powers in the course of a criminal investigation. However, there has been a significant level of quite legitimate public interest in this case, and I would there like to release that information into the public domain. This of course requires your consent. GSK has regularly asserted that it has nothing to hide in this matter and so I should be grateful if you could confirm in writing your consent to the release.
Finally, I have no doubt that the content of this letter will be the subject of numerous Freedom of Information requests to the Agency in the coming weeks. The MHRA takes the view that any considerations of confidentiality are outweighed by the public interest in disclosure, and we will therefore be publishing this letter today alongside our investigation report.
If you have any queries about the contents of this letter, please do not hesitate to contact me.
April 24, 2008
Glaxo refuse to co-operate and release documents to the public
Unfortunately it seems that Glaxo’s reply has not been treated in the same way. The MHRA actually had a reply dated 18 March and a pdf file is hidden away on the MHRA website. Perhaps the MHRA’s embarrassed silence over Glaxo’s reply can be explained by the very final paragraph of the two page letter:
“Finally, it is our strong wish to be as transparent as possible in disclosing information around this investigation. However, from GSK’s standpoint there are legitimate concerns which would need to be addressed prior to any disclosure. These include, for example, the identification of individual employees, independent clinicians and patients, as well as the need to preserve commercial confidentiality of certain information. On this basis, we would be happy to consider requests for information, under the Freedom of Information Act, on a case by case basis in relation to specific documents or categories of documents.”
There you have it. GSK will consider FOI requests (which will have to sent to the MHRA as the FOI Act does not cover GSK) to release “specific documents or categories of documents”.
The only problem is that one can’t ask for“specific documents or categories of documents” as the MHRA can’t release any information into the public domain without GSK’s consent, so we don’t know which document to ask for. Oh and another thing – approximately 1,000,000 pages of documentation were reviewed by the MHRA in its investigation.
So – we’re looking for a needle in a haystack, but we’re not allowed to know which haystack it’s in or even if it’s in a haystack – or even if it’s a needle we’re looking for.
GSK is in no way being “as transparent as possible” in this matter – their reply to the MHRA is a de facto refusal to release any of the information the MHRA has reviewed.
To read the full MHRA report on the investigation read here.
Glaxo on trial in Philadelphia…
Sept. 15 (Bloomberg) — An executive of GlaxoSmithKline Plc, the world’s second-biggest drugmaker, talked about burying negative studies linking its antidepressant drug Paxil to birth defects, according to a company memo introduced at a trial.
“If neg, results can bury,” Glaxo executive Bonnie Rossello wrote in a 1997 memo on what the company would do if forced to conduct animal studies on the drug. The memo was read during opening statements in the trial of a lawsuit brought by the family of a child born with heart defects.
The Philadelphia trial is the first of more than 600 cases alleging that London-based Glaxo knew Paxil caused birth defects and hid those risks to pump up profits. The drug, approved for U.S. use in 1992, generated about $942 million in sales last year, 2.1 percent of Glaxo’s total revenue.
Glaxo officials urged scientists to withhold information about Paxil’s risks from a paper laying out the company’s “core safety philosophy” for the drug, said Sean Tracey, a lawyer for Kilker and David, in his opening statement in the trial.
Glaxo guilty in Philadelphia…
A family has been awarded $2.5m (£1.6m) in damages after a jury in Philadelphia decided that the British-made antidepressant Seroxat was responsible for their three-year-old son’s heart defects.
Thousands of women worldwide have taken antidepressants such as Seroxat in pregnancy, assured by manufacturers and doctors that they are safe. The case is one of a number in the US and the first to end in a verdict against the company.
The full story is here.
Glaxo’s patent for Seroxat/Paxil has long since run out, and the business has moved on, past the hiccup that was Seroxat/Paxil.
Billions of dollars were made by sales of the drug, but now, without a patent, Glaxo is no longer interested. So that’s almost an end to the story, I guess. Seroxat is still prescribed, but less and less these days without Glaxo’s aggressive marketing lies to push it.
In fact, in 2010, Glaxo announced that it will cease discovery work in depression, a pivotal part of its historical neuroscience activity, in an effort to save costs. This marked a symbolic shift for GSK, which generated billions from sales of its antidepressants Wellbutrin and Seroxat/Paxil, with Seroxat in particular sparking criticism from regulators and a series of litigations against the company.
Said CEO Andrew Witty “…it was increasingly difficult to make a decent return on depression research.”
Witty also claimed that the closure of depression R&D did not have anything to do with past litigation problems, saying that antidepressants were “among the most expensive, high-risk” drugs with weak “endpoints” that made it difficult to measure likely success until late in the development process.
Too hard “…to make a decent return…”? So that’s it – there’s no money in antidepressants. There’s certainly no money in trying to help the tens of thousands of people around the world have been harmed – all in the name of profit.
The past is gone and Glaxo does not care how many people it damaged with Seroxat/Paxil and its rigged drug trials.
It’s a truly shocking story… but one that’s not quite over yet…