Seroxat : The Mainstream Media Investigates Again

The Seroxat scandal was originally brought to mass public consciousness by the BBC with their groundbreaking expose “The Secrets of Seroxat” in October 2002.  Since that time a multitude of documentaries , blogs, news articles , forums , comment and opinion on Seroxat and the dangers of other SSRI medications has followed. For the past year, the mainstream media have been fairly quiet on the Seroxat situation, but in the last week, the excellent Sarah Boseley of the Guardian newspaper UK has once again began to investigate the dangers of Seroxat and SSRI drugs.

Here are the links to her new articles :

http://www.guardian.co.uk/society/2009/aug/07/antidepressants-drugs-health-risk

• , Friday 7 August 2009 22.10 BST
• Article history

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

Seroxat antidepressant pills. Photograph: Jack Sullivan/Alamy

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 againstGlaxoSmithKline. 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.

http://www.guardian.co.uk/society/2009/aug/07/paxil-seroxat-antidepressants-glaxosmithkline

Family’s story: antidepressants to blame for child’s defects?

• , Friday 7 August 2009 22.10 BST
• Article history

Kaden Mendoza has just turned seven. His parents, Deborah and Kevin, gave him a big party. They do it every birthday. “It is another year that he has made it through,” says Deborah.

Kaden has undergone open heart surgery three times, the first when he was nine weeks old. “We didn’t find out about Kaden’s heart condition straight away and we almost lost him,” says his mother.

The fourth chamber of his heart was not visible on the ultrasound scan she had when she was pregnant. They didn’t know it was because it was not fully developed. He was two months old when she took the baby to the doctor because he was not breastfeeding.

“His lungs were full of blood,” she says. That was on 22 September 2002. On the 24th, he was airlifted to San Francisco from their home in Washington for his first heart operation.

Throughout her pregnancy, Deborah Mendoza had been taking the antidepressant Paxil, known in the UK as Seroxat. It had been prescribed by the doctor she had seen when she had a panic attack. It was a one-off, a bit of a funny turn, but her father had suffered from the same thing and had been on medication. So she took the advice and started on the tablets in June 2001.

Six months later, she was back at the doctor’s surgery for a different matter. “When I found out I was pregnant, I was concerned and asked if it was alright to take while pregnant, and they said yes,” she said.

Even so, she tried to stop, but found she could not. “It was awful. I was throwing up non-stop.” It was nothing to do with the pregnancy, she said. She was having withdrawal symptoms. “I called my sister and I was just laying there saying, ‘this is awful’.”

She went to see another doctor and was told it would be better to stay on the drugs through her pregnancy.

When Kaden’s heart defect was diagnosed, she had no idea that Paxil might have been responsible. It was not until 2005, when the Food and Drug Administration put out a warning that she realised what might have happened. The family is now suing GlaxoSmithKline, makers of Paxil.The future for Kaden does not look bright. His condition was made worse by complications after the insertion of an artificial tube into his heart. “He will need a heart transplant within two to ten years,” his mother says. “And there is a 50% chance he will need another one after that. He suffers a lot. He loves sports. He is so good at golf and baseball and basketball, but he can’t play them because he runs out of breath.

“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.”

http://www.guardian.co.uk/society/2009/aug/07/women-antidepressant-birth-defects

Women given antidepressant that can cause birth defects

Revealed: GPs still prescribing pill, despite evidence of risk in pregnancy

Sarah Boseley , Guardian UK , 7/08/2009

Thousands of women in the UK may be taking antidepressants prescribed by their GPs without knowing that the pills, which are hard to stop taking, could cause birth defects in unborn children.

The problems relate to a class of drug known as SSRIs (selective serotonin reuptake inhibitors), which includes Prozac and, in particular, the British-made Seroxat.

Several studies have shown a link to birth defects, particularly malformed hearts, in a small proportion of the babies born to women who were taking the drug in the early weeks ofpregnancy.

Most GPs in the UK believe that these drugs are safer than older antidepressants. Seroxat has been marketed to women as a drug to relieve anxiety and depression.

In the US, the Food and Drug Administration, which licences medicines, issued a warning in 2005 and changed the status of Seroxat, which is sold there under the brand name Paxil. The FDA warns doctors “not to prescribe Paxil in women who are in the first three months of pregnancy or are planning pregnancy, unless other treatment options are not appropriate”.

The UK regulator, the Medicines and Healthcare products Regulatory Authority (MHRA) wrote to doctors telling them to prescribe Seroxat for pregnant women only when the benefits outweigh the risks. The National Institute for Health and Clinical Excellence (Nice) also urged caution.

But experts including Dr Tim Kendall, joint director of the National Collaborating Centre for Mental Health which wrote the Nice guidelines on depression, say GPs are still giving SSRIs to pregnant women and other women of childbearing age without warning of the potential dangers.

Most psychiatrists he knew would no longer prescribe Seroxat, said Dr Kendall. “But in primary care it is still quite widely prescribed. GPs are quite flooded with advice. It is unlikely they will have picked up a specialist piece of advice from Nice about mental health.”

In the US, a series of legal actions is about to begin. Lawyers representing women suing the manufacturer of Seroxat, GlaxoSmithKline, say the British company knew or should have known about the birth defects more than 10 years ago. GSK denies it, saying it told the authorities as soon as it was aware of the issue.

All the SSRIs are implicated. According to David Healy, professor of psychiatry in Bangor, Wales, who has been asked to give evidence in the US cases, the rate of birth defects is doubled from 2% in the general population to 4% of those on the drugs. The rate of major defects rises from 1% to 2%. The general rate of miscarriages is 8%, but 16% of women on Seroxat miscarry.

Concern about depression in pregnancy has grown in recent years. Midwives at antenatal clinics are increasingly encouraged to ask pregnant women about their mood and feelings, to pick up any signs of depression which could cause them to harm themselves or fail to bond with the baby when it is born. Talking therapies should be an option but are often in short supply.

Kendall believes the issue of the SSRIs in pregnancy needs to be addressed. “They are addictive,” he said. “The question is should we warn young people before they take them that if they think they might be wanting to get pregnant, these drugs are quite hard to get off?”

“From the late 1980s there was work which very clearly showed that the SSRI group of drugs ought to be regarded as posing a high risk of birth defects to women in the early stages of pregnancy or when they didn’t even know they were pregnant,” said Healy.

One of the SSRI manufacturers, Pfizer which made Zoloft, indicated in the prescribers’ bible, the British National Formulary, that their drug was not recommended for women who might become pregnant. This warning, said Healy, “probably did very little to deter women from taking the drug or doctors from prescribing it, but GSK went further and actually promoted the drug to women of childbearing age”.

All SSRIs pose a risk, said Healy. The danger with recent warnings from the FDA and MHRA about Seroxat is that GPs will switch women to another drug of the same class.

Emily Jackson, professor of law at the London School of Economics, believes there may be a case for legal action in the UK. Cases could potentially be brought against either the GP or the manufacturer for a failure to warn of potential risks.

“The group of patients who often receive an inadequate warning are women who are not currently pregnant or trying to become so, but who are not warned that there is a danger that they will become addicted to paroxetine [Seroxat] while they are not pregnant, and will find themselves unable to stop taking it once they become pregnant, perhaps many years later,” she said.

She raises the possibility of an action under the Congenital Disabilities Act of 1976 on behalf of a child injured by antidepressants prescribed for the mother.

She compares the “no alcohol” message put out by the department of health to pregnant women to the “more equivocal advice” on Seroxat and pregnancy. In both cases, she says, “it seems that women are not to be trusted with making choices for themselves”.

GlaxoSmithKline argues there is still insufficient scientific evidence to prove that the drugs directly cause defects.

A spokesman said: “Tragically, birth defects can occur whether or not the mother was taking medication during pregnancy. We have monitored reports of foetal exposure to paroxetine since the first studies of the drug and there was no indication of increased risk from studies, adverse event reports or any other source until the summer of 2005.

“As soon as we became aware of a potential increased risk, we promptly notified regulatory authorities and physicians.  We strongly believe that doctors should be advised of the potential risk of medicines before prescribing them, and the potential risk of paroxetine use during pregnancy is detailed in the information provided with the medicine.”