The deceptive marketing of Paxil/Seroxat

Hear Alison Bass (author of side Effects, the story behind the deceptive marketing of Paxil) interviewed about her book and corruption in the medical profession. As Alison reveals in Side Effects, GlaxoSmithKline hired a ghostwriting firm, Scientific Therapeutics, to write the first draft of the controversial Paxil study 329. That draft concluded that Paxil was effective and well tolerated in adolescents, even though the actual data in the clinical trial showed otherwise. See back story here.

Indeed, in its re-examination of clinical trial data for all the antidepressants, the FDA labeled study 329 a negative study, finding that Paxil was no more effective than placebo in treating depression in adolescents. Yet Martin Keller, the principal investigator of the Paxil study, and his co-authors, did not object to the ghostwritten version of the study and despite its inaccuracies (which were flagged by peer reviewers), the study was published in The Journal of the American Academy of Child and Adolescent Psychiatry in 2001 and used by GlaxoSmithKline to heavily flog the drug for use in children and adolescents.

Why were the authors of study 329 so lax in attaching their names to a study they didn’t write? Could it have had anything to do with the fact that Keller and several of his co-authors were getting paid huge amounts of money in consulting and speaking fees by GlaxoSmithKline?

Some of my related posts to Study 329 and Marty Keller can be found here.

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Professor David Healy meets with the MHRA to talk SSRI withdrawal reactions

Notes of the 26 June 2009 meeting – thanks to Bob Fiddaman at Seroxat Sufferers.

I find it unbelievable that all too many GPs still know next to nothing about withdrawal reactions from SSRIs.

Prof Healy considered that there was little evidence available on how to manage patients who had difficulty withdrawing from SSRIs. All agreed that this was a very difficult area to study as the management of the patient would differ depending on the patient.” Maybe if the drug companies would start by admitting there is a problem we could begin to look for some answers.

Unfortunately all the drug companies take the same stance that Glaxo has with Seroxat/Paxil – problem, what problem??

Still, we should get some answers in the Autumn of 2010 – that’s when the High Court in London is scheduled to hear the start of the UK class action against Glaxo and Seroxat. I, for one, cannot wait to follow this trial and see all the secret documents that have been hidden from the public for so long by Glaxo.

Open Court – that’s what we want – let’s have everything out in the full glare of the world’s press.

Anyway – here are the notes from Prof Healy’s meeting with the MHRA:

Meeting to discuss awareness and management of withdrawal reactions with SSRIs and related antidepressants
Attendees:
Professor David Healy
Mrs Sarah Morgan
Dr Julie Williams
Ms Diane Leakey

1. Introductions and background
MHRA explained that the background to this meeting was a meeting held with Mr Fiddaman in September 2008. Mr Fiddaman had raised concerns about a lack of awareness on the part of health professionals of withdrawal reactions with SSRIs and related antidepressants. Prof Healy explained that he had had a long term involvement with the safety of SSRIs and that he received a large number of e-mails directly from people withdrawing from SSRIs asking for advice on management of withdrawal symptoms. Before the meeting Prof Healy had provided documents that he had produced relating to the management of withdrawal from SSRIs.

2. Existing advice on management of withdrawal reactions with SSRIs/SNRIs
All agreed that most health professionals get their information from guidelines issued by the National Institute for Health and Clinical Excellence (NICE) and the British National Formulary (BNF) rather than directly from the Summaries of Product Characteristics (SPC), although it was noted that the SPC was very important as it dictated the information that would be available to the patient through the Patient Information Leaflet. MHRA informed Prof Healy that they had provided input to the recent consultation for revision of the NICE depression guideline and that the revised guideline would be available towards the end of the year. MHRA had also informed the BNF that they were looking at the area of withdrawal reactions and would contact them in the future regarding proposals for updates to the relevant sections of the BNF. MHRA also raised the important role played by Prescribing Advisors in the Primary Care Trusts in influencing prescribing practice. Prof Healy said that a key point not included in the guidance currently available was the existence of liquid formulations of SSRIs which could be useful in the management of withdrawal to allow slow tapering. Prof Healy also stated that before treatment started there should be a discussion between the prescriber and the patient about the possibility of withdrawal reactions.

3. Awareness of withdrawal reactions in clinical community
Prof Healy expressed the view that general practitioners (GPs) were not aware that withdrawal reactions on stopping SSRIs could be prolonged in some patients and were not aware of how to manage withdrawal reactions in these patients. Prof Healy was concerned that GPs may instinctively advise patients to withdraw by taking tablets on alternate days and this was not an appropriate approach.

4. New evidence relevant to management of withdrawal reactions
Prof Healy was not aware of any new evidence relevant to the management of withdrawal reactions. When asked if he had a view on the size of the problem of serious and prolonged withdrawal reactions with SSRIs, Prof Healy said that this was not possible to measure. Prof Healy said that while the propensity of an SSRI to cause withdrawal reactions was often thought to be only related to the half-life of the
drug, this seemed unlikely to be the case – it could also be related to the potency of the different drugs at the serotonin reuptake site. The lack of understanding of the problem contributes to a lack of effective solutions.
MHRA asked whether in his view there was any way that patients who were more at risk of prolonged withdrawal reactions could be identified. Prof Healy said that he felt that from his experience women seemed to be more at risk than men but it was unknown whether this was because more women than men were treated with SSRIs. MHRA said that their review of the issue had not identified any link between the risk of withdrawal reactions and the gender of the patient. Prof Healy considered that there was little evidence available on how to manage patients who had difficulty withdrawing from SSRIs. All agreed that this was a very difficult area to study as the management of the patient would differ depending on the patient.

5. Dependence/withdrawal for women of child-bearing years
Prof Healy had asked for the issue of use of SSRIs in pregnancy to be included in the agenda. He said that it was an important issue and the subject of upcoming court cases in the USA. Prof Healy said that it was important that women of childbearing years were appropriately informed of the risk of withdrawal reactions with SSRIs before beginning treatment and stated that in his view doctors may be liable under the Congenital Disabilities Act 1976 if they did not adequately inform patients of the risks of treatment during pregnancy.
MHRA said there had been communications about a small risk of congenital malformations associated with paroxetine and this issue was under further discussion at EU level. Prof Healy highlighted a recent publication describing an animal study looking at reproductive toxicity of a variety of SSRIs. MHRA asked for the reference and to be kept informed of any further new evidence of relevance to this issue.
MHRA noted that NICE had published its antenatal and postnatal mental health: clinical management and service guidance and that it was important that NICE was kept informed of any new evidence or advice in this area. MHRA agreed to find out whether review of the guideline was planned and to let Prof Healy know the best contact point for communication on this issue. Post meeting note: Prof Healy confirmed post-meeting that he had contacted NICE on this issue.

6. Opportunities for better communication with health professionals
Prof Healy said that the focus should be on highlighting to GPs that withdrawal reactions could be serious and prolonged in some patients and agreed that NICE and the BNF would be reasonable routes.

7. AOB
MHRA thanked Prof Healy for attending the meeting and agreed that it would be important to keep in contact on important new evidence in this area.

Seroxat/Paxil – the new Thalidomide? – part 3

Part 3 of this story…

Seroxat/Paxil – the new Thalidomide?

Seroxat/Paxil – the new Thalidomide? – part 2

Reading the above stories (and from doing a little reasearch online), it would seem to me that, at the very least, Glaxo would err on the side of caution and advise that pregnancy and Seroxat/Paxil perhaps do not mix – they might say the jury was out, but at least be advised they might be a problem.

That would be safe, reasonable and logical you would think.

But no.

Glaxo are instead trying to create a new market from Paxil/Seroxat – as a treatment for premenstrual dysphoric disorder… the clincial trials they have funded say just take Seroxat/Paxil for a few days each month and all will be well!

Honestly, from my own experience (and the experience of tens of thousands of others, the ABSOLUTE LAST THING you would ever want to do is to take Seroxat/Paxil for 6 days then stop, then do the same again each month.

What is Glaxo thinking about? Profit – pure and simple – a new way to patent Seroxat/Paxil.

Read more:
Just take Paxil for 6 or 7 days a month…. every month!

Seroxat/Paxil for Pre Menstrual Syndrome – no conflicts of interest…?

Seroxat/Paxil – the new Thalidomide? – part 2

This from Professor David Healy writing in the Guardian today:

Doped and duped

Adverse effects of widely-prescribed drugs are often overlooked because there is so little truly independent academic evidence

Since 2005, the SSRI paroxetine, first marketed by GlaxoSmithKline as Seroxat, has carried warnings of risk of birth defects. In the US litigation in which I have been asked to give evidence, the plaintives will argue that, even before they were launched, there was good laboratory evidence that the SSRIs might cause problems, and, following their initial marketing, evidence emerged over a decade ago from clinical use that the drugs actually do cause problems.

Yet these drugs have been actively promoted, de facto primarily to women of child-bearing years. How could this happen?

Part of the problem is that having gone to their GP with a nervous problem, many women become dependent on a prescribed SSRI and find it impossible to stop using it whether they wish to get pregnant or if they find they are pregnant while on treatment. But few, if any, of these women will have been informed of either the risk of birth defects or the risk of becoming addicted. Why not?

What we are seeing here is the astonishing marketing power of pharmaceutical companies, which can now effect huge changes in medical culture within months. In this case, a great part of the scientific literature (the primary marketing tool of companies) on the use of antidepressants in pregnancy and on dependence on antidepressants is ghostwritten – just as virtually all literature on giving antidepressants to children was, at one point, company-written. Firms of medical writers are contracted to pharmaceutical companies to place in academic journals articles attributed to, but not actually authored by, university researchers.

Because of this, guideline makers like Nice, which can only go by the published literature, are trapped. Regulators, like the FDA and MHRA, which reflect a professional consensus rather than lead on issues like this, are likewise stuck. Doctors who believe their role is to follow Nice, the MHRA and the scientific evidence are in the same bind.

The process of manufacturing clinical consensus has become so slick that it is now almost impossible to find independent articles from academic physicians with no links to industry that will sound a note of caution about prescribing antidepressants to women of child-bearing years. This is a problem that increasingly applies across all of medicine – from the use of HRT, to drugs for osteoporosis, respiratory or gut problems, pain-relief, as well as all psychotropic drugs.

Where once drugs were seen as poisons to be used judiciously and with caution, they are now treated as fertilisers whose more or less indiscriminate use can only do good. Where once farmers knew to keep their cattle out of fields growing the serotonin reuptake inhibiting weed, St John’s Wort, as it caused miscarriages, under industry influence women have been herded by doctors in exactly the opposite direction.

So the question must remain just how much did Glaxo know and when did they know it?

Glaxo has a track record of hiding negative clinical trail data that would knock sales of its drugs – the story of Seroxat and Study 329 is truely shocking.

Read more here:
More on Paxil and suicide – “Glaxo was aware of this risk, and hid it”

and here:
Let down by the MHRA… again

and here:
Glaxo fails in its responsibility to patients and it hid Seroxat data – it’s official

Seroxat/Paxil – the new Thalidomide?

This from Sarah Boseley at the Guardian:

Antidepressants once seen as miracle drugs: now risks are becoming evident

US courts to hear claims that insufficient attention was paid to dangers to foetus

Since the horror of the Thalidomide scandal in the 1960s, pharmaceutical companies and medicines regulators have been acutely aware of the dangers drugs may pose to the unborn child.

Establishing what the effect of a drug may be on a foetus, however, is no simple task. Companies must rely on animal studies in the early stages of research and hope that the drug will behave in humans in the same way. Trials on pregnant women are rarely carried out, for obvious reasons.

Depression and anxiety became big business for the pharmaceutical industry in the 1990s as doctors became better at diagnosing the problems, exposing a population of over-achieving, highly-stressed, worried-well.

Women, always more willing to see a doctor than men, were a large proportion of those diagnosed and put on SSRIs (selective serotonin reuptake inhibitors) such as Prozac and the British drug Seroxat, known as Paxil in the US. For a while, these seemed to be the new miracle drugs. They were safer than older antidepressants because the severely depressed could not overdose on them.

But in court cases about to begin in the US, it will be argued that insufficient attention was paid to the possible dangers for young women who were pregnant or might become pregnant and more particularly, for their babies.

Twenty years ago, when serotonin, a chemical which sends messages to the brain, was under investigation, it was recognised that it was likely to have an effect on the developing foetus, according to David Healy, professor of psychiatry in Bangor, Wales, and an expert witness in the legal action against GlaxoSmithKline. It was not just a neurotransmitter, but played a role in organ development in the embryo.

Animal tests appear not to have been reassuring, he says. By 1991, a study by Shuey and Lauder had shown that all SSRIs were potentially teratogenic – could cause birth defects – in animals, albeit in small numbers. GSK denies this. “The animal and human studies did not show teratogenicity, and were made available to regulatory agencies as part of the approvals,” said a spokesman. But based on Lauder’s work, Pfizer which made a rival drug, Zoloft, recommended that women on their drug “should employ an adequate method of contraception”.

Datasheets

GSK launched Seroxat in 1992. It was recognised that insufficient work had been done to establish the safety of any of the SSRIs during pregnancy, and as a result, throughout the 1990s, the standard statement on the drug datasheets which go to doctors was that they “should not be used during pregnancy or by nursing mothers unless the potential benefit outweighs the potential risk”.

But pregnant women become depressed too. “I think depression is generally underestimated in pregnancy,” said Dr Tim Kendall, joint director of the National Collaborating Centre for Mental Health in the UK. “It is much more common than people think. It used to be thought you gave birth and you are suddenly depressed – the withdrawal of all those oestrogens. But in fact people who have postnatal depression are quite commonly depressed before the birth.”

GSK began to market Seroxat as the SSRI of choice for women who were depressed and pregnant, or might become pregnant, says Healy. GSK says marketing to women of childbearing age was valid, as women make up a high proportion of those diagnosed with depression and anxiety and most would be of childbearing age.

Seroxat was positioned as the best SSRI in cases where the benefits of treating depression outweighed any risk. It was found in only low concentrations in breast milk, the company said, which meant that breastfeeding would not be a problem. It pointed to studies which showed children born to mothers on Seroxat had no mental or behavioural problems.

GSK also argued that depression itself could harm the baby because an untreated mother is more likely to smoke, drink and take drugs and maybe even to harm herself. Healy says there is no evidence relating to women with depression during pregnancy – only to those who were diagnosed with postnatal depression.

From 2000, GSK in the US was running a targeted promotional campaign to increase sales of Paxil to pregnant women and women of reproductive age. The Mother Knows Best Campaign had three main objectives: to raise awareness of its greater claims for safety than other antidepressants, such as the low Paxil levels in breastmilk, to educate doctors and consumers generally on the benefits of the drug for women of childbearing age and to encourage women with depression to ask specifically for Paxil.

Influential psychiatrists, called in the business “key opinion leaders” were recruited to give talks and author articles on Paxil’s safety for mothers to be.

But in February 2005, the Lancet published an analysis of almost 100 cases from the World Health Organisation’s adverse drug effects monitoring centre in Sweden of babies who suffered from convulsions and other withdrawal symptoms after birth because their mother had been taking an SSRI for depression during her pregnancy.

The effects were most marked on Seroxat, it said, and recommended that all SSRIs “should be cautiously managed in the treatment of pregnant women with a psychiatric disorder”.

Malformations

In 2003, the Food and Drug Administration (FDA) which regulates medicines in the United States had asked GSK to look at the incidence of birth defects on Seroxat, or Paxil. In 2005, the company handed over a retrospective epidemiological study which found an increased risk of major congenital malformations in the babies of women who took it in the first three months of pregnancy.

GSK pointed out that data from other places did not show up a problem. Nonetheless, the FDA changed the pregnancy warning from category C, meaning not enough research has been done to be sure of safety, to category D, meaning there are signs it may not be safe.

“FDA is advising patients that this drug should usually not be taken during pregnancy, but for some women who have already been taking Paxil, the benefits of continuing may be greater than the potential risk to the foetus,” it said.

A later advisory notice from the FDA drew attention to a raised risk of a life-threatening lung condition called persistent pulmonary hypertension in babies whose mothers took Paxil later in pregnancy – up sixfold from the usual level of one or two per 1,000 babies born in the US. But at the same time it pointed to a study in the Journal of the American Medical Association showing women who stopped taking antidepressants while pregnant were five times more likely to relapse.

GSK insists that their drug has only ever been promoted for those who need it – in the case of pregnant women, those in whom the dangers of depression are greater than any possible risk from the drug. “GSK appropriately marketed paroxetine for use by the patients for whom it was indicated and who could benefit from it,” said the company in a statement.

“…GSK appropriately marketed paroxetine for use by the patients for whom it was indicated and who could benefit from it…”

Yeah, right…

Read this story as well:

“It is hard not to be upset with GSK. No amount of money can ever make up for what’s happened and what will continue to happen to Kaden.”

Rewriting the Psychiatrist’s Bible

On the radio in the UK tonight – BBC Radio 4, Tuesday 4 August, 20.00

Afterwards it’ll be available via BBC iPlayer.

Matthew Hill investigates the links between psychiatrists and the pharmaceutical industry. Should there be increased transparency over top psychiatrists’ links to the industry?

He looks at the influence of the Diagnostic and Statistical Manual of Mental Health Disorders (DSM), produced by the American Psychiatric Association (APA), which has been heavily criticised in the past for a lack of transparency between the panel members and pharmaceutical companies. Matthew also examines the ‘Chinese menu’ aspect of the DSM’s diagnostic criteria and the sheer number of conditions it includes. Matthew investigates whether the APA’s transparency policy goes far enough and if we are medicalising real conditions or just traits of human personality.

Read more – or just enter ‘DSM’ in search box on the left.
Look out – DSM V is just over the horizon
Diagnostic and Statistical Manual of Mental Disorders: turning normal behaviours into sickness

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