Dark secrets lurking in the drugs cabinet — (The Observer)

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The Observer

Sunday 7 November 2004

Jamie Doward and Robin McKie

Seroxat was hailed as the wonder pill. Now it is at the centre of a new controversy

Hailed as one of the greatest additions to the medicine cabinet since the invention of antibiotics, the antidepressant Seroxat has become a symbol for all that is wrong and suspect about the pharmaceutical industry today.

It was supposed to be a cure for most of the woes of the modern world, a happy pill that would banish the misery of depression and gloom. Now it is seen by an increasing number of campaigners, academics and doctors as a dramatic illustration of our inability to control the behaviour of drug companies. As evidence mounts about the uncontrolled use of anti-depressants, pharmaceutical companies have responded simply by trying to find new conditions they could market as targets for these controversial drugs.

And while the government last week indicated it was considering plans to break the close links with the pharmaceutical industry and the nation’s drug watchdog group, the Medicines and Healthcare products Regulatory Agency (MHRA), many experts feel the move could be doomed to failure, particularly when it comes to antidepressants and other medicines for emotional problems.

‘It would be good to get impartial advice but it is difficult in practice for any academic in the field to gain expertise in drug action without having to interact with the pharmaceutical industry,’ said Professor Til Wykes, director of the UK mental health research network. ‘That makes it very hard to avoid accusations of partiality.’

Seroxat and Prozac are the most widely used members of drugs called SSRIs – selected serotonin re-uptake inhibitors. Studies suggest serotonin plays a key role in affecting a person’s emotions. Increasing serotonin levels is considered an antidote to depression. SSRIs act within the brain to do just that: increase serotonin levels.

Unlike most drugs, however, SSRIs were specifically designed – as opposed to discovered – as a treatment for depression. Seroxat was introduced 14 years ago. Apart from being an antidote to depression, it would allow, it was claimed, hyperactive children to lead normal lives, and stop those with obsessive-compulsive disorders from harming themselves. It was also cheap and had only slight side effects, said its makers.

Several million people were given the drug in Britain, including more than 50,000 children. Everything seemed to go well – for a while.

Then stories began to circulate about suicides and self-mutilation and the Seroxat hype began to unravel. An internal GlaxoSmithKline memo written in 1998 revealed that trials in children actually showed it was no better than a placebo in alleviating depression. ‘It would be commercially unacceptable to include a statement that the efficacy had not been demonstrated, as this would undermine the profile (of the drug),’ the memo stated.

Worse, when the company examined the details of its trial data, it found that more of the children on the real drug, compared with those on a placebo, had suicidal thoughts. A typical case that made tabloid headlines recently was that of 18-year-old Jamie Hoole who started taking Seroxat. He responded well to his daily 20mg regime. But soon his depression returned.  Jamie – a promising musician – became increasingly anxious. He started to cut his arms and legs. Finally he hung himself. The coroner at his inquest said Jamie’s death may have been ‘wholly or in part’ linked to Seroxat.

‘Jamie got worse and worse and it was frightening,’ said his mother, Jean. ‘I thought the doctors would take him off it. They didn’t. But nobody has had the full facts before taking this drug. That makes me angry.’

The issue is not that SSRIs are overwhelmingly deadly but that there is a real danger in prescribing them for young people and emotionally sensitive individuals. One US study, using UK data, revealed that anti-depressants are linked to suicidal thoughts during the first few weeks of their use, but that these effects wear off. In short, these antidepressants can be helpful for some people but great care must be taken in prescribing them, a point that appears not to have been hammered home until very recently.

A survey carried out by the mental health charity Mind, in collaboration with Panorama, found that 97 per cent of respondents knew of someone who had experienced unwanted or uncomfortable reactions to Seroxat. These included: reduced sexual desire, sleep problems, fatigue, irritability and sweating. One in five reported violent behaviour. Half who had experienced a reaction had feelings of self harm or suicide and more than four out of five experienced withdrawal problems.

These findings are backed by other studies which have also noted these effects are far more pronounced in younger people. As a result the MHRA finally issued guidance which outlawed the prescription of the drug to under-18s. Last year European watchdogs also recommended extra care be taken in prescribing Seroxat for people under 30.

Such advice flies in the face of pharmaceutical practice, however. While health regulators are now becoming increasingly anxious to control the use of Seroxat and other antidepressants, drug companies – equally anxious to gain as much income as possible from their medicinal cash cows – are trying to expand their uptake.

GlaxoSmithKline has made billions out of Seroxat and sees no reason why this should halt, it would appear. One of its internal marketing documents shows the company planned to double sales by targeting people who suffer from a widely recognised condition known as social phobias.

‘But they changed the words,’ said Professor David Healy, a psychopharmacologist at Cardiff University. ‘They called it social anxiety disorders. Phobias imply a behaviour that can be treated by therapy. Anxiety disorder implies it is more about drugs.’

In addition, GSK has marketed the drug as the answer for people who suffer from post-traumatic stress disorder. Such projected uses are far from those that were originally envisaged for the drug as a general treatment for clinical depression.

This point is not denied by GSK, however. A spokesman told The Observer that Seroxat could be marketed for new conditions but insisted that this would only be done after stringent tests had been carried out. ‘Medical authorities around the world have required that GSK study each condition separately in order to prove benefit in each con dition specifically,’ he s
aid.

‘With more than 13 years of safety and effectiveness data on Seroxat that has been built from use by patients all over the world, as well as clinical trials involving 24,000 patients, there are few medicines that have been studied in as much detail. As with all important medicines, Seroxat and other SSRI anti-depressants can cause side effects in some people. Information about these is provided to doctors and patients and is updated as we learn more from clinical trials and the monitoring of patients world-wide.’ He added: ‘Seroxat is an important medicine designed to treat serious psychiatric diseases. These disorders can be severe, distressing, debilitating and potentially deadly.’

Richard Brook, Mind’s chief executive, writes in the latest issue of the Journal Of Mental Health: ‘The trouble is that pharmaceutical companies form a massive part of the UK economy and have to survive in a ruthless commercial environment. They exert a pervasive influence over the research into and use of medicines. Virtually all research on drugs – 70 per cent of trials reported in major medical journals – is funded by the industry. Drug companies therefore have a hugely disproportionate influence on what gets researched, and also how it is researched, how the results are interpreted, and how – and crucially whether – the results are reported.’

Among the accusations now levied against the drug firms are that they ‘ghost’-write medical journal articles published by leading doctors, sponsor conferences and other medical training events and pay large fees to doctors to talk about their products.

‘They have all the data on their new products and before any independent person can get at the data it takes months or years, so that inde pendent information limps a long way behind the commercially driven information and is in a much lower volume,’ said Dr Andrew Herxheimer, founder of the Drug and Therapeutics Bulletin, in evidence to the parliamentary select committee currently hearing evidence on the influence of the pharmaceutical industry. ‘The funding for that is extremely small compared with the industrial funding of promotion; so that creates an overwhelming imbalance.’

Nor is the problem helped by the nature of the MRHA. The agency is an opaque organisation that has long been the target of campaigners who accuse it of being completely funded by the pharmaceutical industry. It is not, but the secrecy of its behaviour does not help. In contrast with the FDA in the US it does not publish the results of its trials on a publicly accessible website.

‘You cannot get access to the good points or the hazards. They’re incredibly secretive,’ Healy said. ‘You could have experts having close links, providing you can see what they say. Then we can make up our own minds.’

Anti-depressants: Ups and downs

The World Health Organisation estimates that by 2020 depression will be the second largest cause of death and disability in the world.

As many as one in three people will experience some form of depression in their lifetime.

Global sales of anti-depressants total more than $17 billion, making them the third best-selling class of drugs in the world.

Studies show 70 per cent of people who take anti-depressants start to feel better after their first prescription.

Anti-depressants reduce the symptoms of depresssion which include loss of interest, sleeping too much or too little and feelings of worthlessness or excessive guilt.

Studies show between 30 and 40 percent of children and adolescents with depression will not respond to an initial medication.

Long-term side effects of taking anti-depressants include sleep disturbances, weight gain and sexual dysfunction.

Early side effects include nausea, diarrhoea, headaches and agitation. These usually disappear within two to three weeks of taking the drugs.