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What price happiness?

In the early 1990s a range of wonder pills seemed to offer a cure for depression with no side effects. Now the drugs are in danger of being banned. What went wrong? Jeremy Laurance reports

12 June 2003

Happiness. It is what everybody wants and nobody knows quite how to get. Some people are born three drinks ahead of everybody else. Others - the sad, the grumpy and the withdrawn - have a low enjoyment of life. Then along comes a little white, torpedo-shaped pill that promises to even out nature's imbalance and inject a little "joy juice" into those whom happiness had passed by.

It may seem astonishing in the light of safety concerns today, but the arrival more than a decade ago of the antidepressants Prozac, Seroxat and their relatives inspired the hope that unhappiness could be banished. The drugs belonged to a new class of antidepressants that were claimed to be better and have with fewer side effects than any that had gone before. They held out the promise of an end to mental suffering.

Such is the burden of misery in the western world that the SSRIs (Selective Serotonin Re-uptake Inhibitors) have become among the mightiest selling drugs of all time. Of the 22 million prescriptions written for antidepressants in the UK last year, most were for SSRIs. Prozac, the best known brand, made by Eli Lilly, was the world's fastest selling drug until it was outstripped by Viagra. Seroxat, made by GlaxoSmithKline, now outsells Prozac in the UK and is estimated to have been taken by 17 million people around the world since it was first licensed in 1990.

However, the warning this week by the Department of Health that Seroxat should not be prescribed to under-18-year-olds because it can provoke suicidal thoughts and impulses could be the first seismic signal of a major earthquake.

The warning comes from the expert panel appointed last month by the Medicines and Healthcare Products Regulatory Agency (MHRA), to review the safety of Seroxat. This followed a BBC Panorama programme last autumn that highlighted claims that the drug has pushed some people into suicide and caused others withdrawal problems, provoking the biggest response in the programme's history with 67,000 calls and 1,400 e-mails.

The expert panel has met twice and is due to meet three to four more times before producing a report that is to be published later this year. If it finds that Seroxat causes similar problems in adults to those already identified in young people, as thousands of users have claimed, it will lead to a serious reappraisal of the use of Seroxat and the other SSRIs. After more than a decade in which it seemed as if medicine might vanquish misery, it is the drug companies who are feeling miserable.

Wind back a decade to Wenatchee, a small American town in Washington State, once known only for its apples. In the mid-1990s it acquired a new, more dubious claim to fame: as the Prozac capital of the world.

Peter Kramer had already published Listening to Prozac, in which he described the drug as a "mood brightener" that could lift the episodically down moods of those who are not clinically depressed without causing euphoria or the side effects associated with energy boosting drugs such as amphetamines. It was Dr Kramer who asked why a person born with too little "joy juice", but who falls short of being clinically depressed, should not be given more.

James Goodwin was one of those who was persuaded by Dr Kramer. A psychologist in Wenatchee, he claimed to have prescribed Prozac, or a close equivalent, to every one of his 700 patients. He argued that everyone is depressed - they just didn't realise it until they took the drug. He became known as the Pied Piper of Prozac.

Even then, in 1994, Dr Goodwin was opposed by a group of patients called the Prozac Survivors Support Group, who claimed the drug could cause personality changes and violent behaviour.

He was also taken to task by a psychiatrist, Peter Breggin, who argued against the widescale prescribing of antidepressants on moral grounds. He was against treating all kinds of misery and wanted suffering reinstated as an acceptable and necessary fact of life. While this represented the extreme end of the debate about the uses to which the new antidepressants might be put, it illustrated an important point about the SSRIs. They were regarded as so clean, safe and effective that non-medical reasons had to be found for not using them.

In 1992 the Royal College of Psychiatrists to launch its Defeat Depression campaign. Here was a new type of antidepressant that did not leave you with a leathery tongue, a sluggish gut and cotton wool between your ears. Depression causes enormous suffering and takes the lives of over 4,000 people a year, many of them young, by suicide. Prozac and its relatives looked like the answer that psychiatrists and their patients had dreamed of.

This is the serious part of the Prozac story and the reason why these SSRIs are important additions to the pharmaceutical armamentarium. Depression is a serious illness. It is not the same as ordinary sadness. Divorce, redundancy, bereavement all cause sadness, but it is when the sadness cannot be shaken off that it acquires the label of depression (though it can also occur without any trigger).

Depression drains the pleasure, as well as the point, from life. People in its grip lose the sense of their own value, and then of the value of anything. They fear being taken for malingerers and feel to blame for their condition. The shame adds to the depression.

Fear of the stigma of mental illness and professional reluctance to investigate emotional problems conspire to keep the suffering hidden. The Royal College of Psychiatrists argued that much of the suffering was unnecessary because with the advent of the SSRIs effective, and acceptable, treatment was now available.

The SSRIs are not mere lifestyle drugs. They are life-savers. But that is not the way they have been portrayed. As prescribing of Prozac and its relatives rose, so did headlines mocking this "pill popping nation".

One of our most serious social ills is our unreasonable fear of psychoactive drugs. Most people have no difficulty with the insulin given to diabetics to control their glucose level, but suggest a pill to boost serotonin levels and they react as if confronted by a drug pusher.

The common view is that people should be able to cope without such chemical aids. Put another way, they should pull their socks up. That is to ignore the mind-numbing paralysis caused by depression. Yet it is true that the exaggerated hopes for the SSRIs made them easier for doctors to hand out. For a busy GP confronted with the sixth depressed patient of the morning, the promise of a safe, effective drug made it simple to reach for the prescription pad.

Many doctors claim that while genuine depression still goes untreated because of the stigma, there are many other patients who are not clinically depressed who are being inappropriately treated with the drugs. In any treatment, doctors have to assess the balance of risk and benefit - the more serious the illness, the greater the risk that can be tolerated. As the threshold for treatment has lowered, so the importance of the risks of the SSRIs has increased.

Last autumn, Colin Whitfield, a retired headmaster aged 56, locked himself in his garden shed in Wales and cut both his wrists while his daughter was asleep in the house. He left no note and in the days before had given no sign that he meant to take his life. He had recently been prescribed Seroxat.

His wife, Kathryn, told Brecon coroner's court that the act was so out of character he could not have been in his right mind and she had "no doubt that it was the drug that caused him to do it". The coroner, Geraint Williams, was so alarmed by the case that he wrote to Alan Milburn, the Secretary of State for Health, asking him to hold an inquiry into Seroxat "and consider whether it should be withdrawn from sale in the UK".

That inquiry is now under way, following similar reports and other evidence amassed over more than a decade. The charge is that these SSRIs cause some patients to become extremely agitated and potentially violent or suicidal when they first start taking the drugs, while others suffer withdrawal symptoms when they try to stop them. One self-help organisation, the Seroxat Users Group, has 4,000 members who claim to have direct experience of problems with the drugs or are relatives of people who have had.

A central problem for the inquiry is disentangling the effects of the drugs from the effects of the condition they are given to treat. Depression is the main cause of suicide and the makers of the SSRIs maintain that their drugs have been unfairly blamed.

But the ban announced this week by the MHRA on prescribing Seroxat to under-18-year-olds is the first official acknowledgement that the SSRIs do increase suicidal thoughts and impulses, at least in the young. The biology of adolescents is said to be different from that of adults, but at the press conference called to announce the ban, Jonathan Chick, a consultant psychiatrist at the Royal Edinburgh Hospital and a member of the Seroxat inquiry panel, admitted there could be problems in adults too. It always puzzled him, he said, why suicide rates in adults taking Seroxat were not lower than among those taking placebo, when he would have expected them to be lower given the beneficial effect of the drugs on depression.

The outcome of the inquiry could be of momentous significance. Like many new drugs, the SSRIs are following a familiar trajectory: soaring popularity on launch as they are hailed as a wonder drug, followed by the emergence of doubts about safety leading to plummeting prescribing.

The hope must be that use of the SSRIs will eventually arrive at a plateau where their risks and limitations are recognised and they are reserved for serious illness. If Seroxat and its relatives were lost it would be a tragedy. If they are saved it will be a lesson in the dangers of hype.

'When I came off Seroxat I wanted to kill myself'

Sian Lloyd-Pennell, Age 38, recovering depressive

I started Seroxat in January 1998, after I'd had a few years of being very depressed. My grandmother had died, I'd come out of a relationship and had an abortion. I went to my GP and was told Seroxat would help with the depression, as well as with social shyness. After the first two weeks, I felt permanently drunk and it didn't help me with depression. I went back and they put the dosage up. Six months on and it still wasn't helping, so they put the dosage up again. You don't argue with doctors. After 18 months of this they took me straight off Seroxat and put me on another drug. I fell apart. I had what felt like electric head-shocks, shaking, nausea... I was on the verge of a breakdown, so they said to go back on Seroxat. Once back on, I started to get night terrors and palpitations. I kept falling sideways everywhere I walked. I also suffered from memory loss and went off sex. Last September I decided to come off Seroxat myself, over a five-week period. For the next five months I was so ill I wanted to kill myself. I couldn't eat or sleep and I had vivid nightmares. Another doctor told me that these withdrawal symptoms were due to Seroxat. I'll try a natural remedy now, like St John's Wort.

I never knew it was anything to do with Seroxat until six weeks after I came off it and found the Seroxat User Group. I didn't realise so many felt the same as me. I haven't been able to go back to work. I have no confidence.

'Prozac was the best thing I ever did'

Natalie Marsh, Age 30, press officer

I went on Prozac in my early twenties following a bout of serious clinical depression. Before that, I tried two years of cognitive therapy which was very helpful but didn't alleviate my symptoms. So I went on to Prozac for a year and it was the best thing that I ever did. Before, I was suicidal and very depressed; my social life and my sleep patterns were affected.

I'm off it now and would have no qualms about going back on again. I think that I will always be at risk of being depressed again, but it doesn't scare me because I know I can take Prozac and feel better. My decision to stop came from me. I felt ready after discussing it with my GP. I've been off Prozac for two years and I feel fine. I've read the reports about antidepressants. Having taken them myself, I feel sympathy for those it has affected badly, but for many people it can be a positive experience.


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