Antidepressant drugs don't work – official study

[Al-khiyal]

Antidepressant drugs don't work – official study

February 26, 2008 -- They are among the biggest-selling drugs of all time, the "happiness pills" that supposedly lift the moods of those who suffer depression and are taken by millions of people in the UK every year.

But 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.

The finding will send shock waves through the medical profession and patients and raises serious questions about the regulation of the multinational pharmaceutical industry, which was accused yesterday of withholding data on the drugs.

It also came as Alan Johnson, the Health Secretary, announced that 3,600 therapists are to be trained during the next three years to provide nationwide access through the GP service to "talking treatments" for depression, instead of drugs, in a £170m scheme. The popularity of the new generation of antidepressants, which include the best known brands Prozac and Seroxat, soared after they were launched in the late 1980s, heavily promoted by drug companies as safer and leading to fewer side-effects than the older tricyclic antidepressants.

The publication in 1994 of Listening to Prozac by Peter Kramer, in which he suggested anyone with too little "joy juice" might give themselves a dose of the "mood brightener" Prozac, lifted sales into the stratosphere.

In the UK, an estimated 3.5 million people take the drugs, collectively known as selective serotonin reuptake inhibitors (SSRIs), in any one year and 29 million prescriptions were issued in 2004. Prozac, the best known of the SSRIs made by Eli Lilly, was the world's fastest-selling drug until it was overtaken by Viagra.

In the study, researchers conducted a meta-analysis of all 47 clinical trials, published and unpublished, submitted to the Food and Drug Administration in the US, made in support of licensing applications for six of the best known antidepressant drugs, including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.

Two drugs were excluded from the study because of incomplete data. A third drug, chemical name nafazodone, has been withdrawn from the market because of side-effects.

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.

That was sufficient to grant the drugs a licence but did not meet the minimum three-point difference required by the National Institute for Clinical Excellence (Nice) to establish "clinical" significance. Yet Nice approved the drugs for use on the NHS in the UK because it only had access to the published trials, which showed a larger effect.

Professor Kirsch said: "Given these results, there seems to be little reason to prescribe antidepressant medication to any but the most severely depressed patients, unless alternative treatments have failed to provide a benefit. This study raises serious issues that need to be addressed surrounding drug licensing and how drug trial data is reported."

Five years ago, there were allegations that antidepressant drugs were addictive and could trigger suicides. All but Prozac were banned for children, although a major investigation on the safety of medicines cleared them of causing suicide in adults.

Alternative treatments for depression, such as counselling or physical exercise , should be tried first, Professor Kirsch said. The pharmaceutical companies had withheld data that was available to the licensing authorities so that doctors and patients did not understand the true efficacy, or lack of it, of the drugs.

"This has been the frustration. It has made it very difficult to answer the question of whether the drugs work. The pharmaceutical companies should be obliged when they get a drug licensed to make all the data available to the public. When you analyse all the trials of these SSRIs, both published and unpublished, it leads you to more sober conclusions," he said.

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."

The new finding would make doctors "much more cautious about prescribing the drugs," Mr Kendall added.

GlaxoSmithKline, makers of Seroxat, said the authors of the study had "failed to acknowledge" the very positive benefits of SSRIs and their conclusions were "at odds with the very positive benefits seen in actual clinical practice." A spokesperson added: "This one study should not be used to cause unnecessary alarm for patients.

Lilly said in a statement: "Extensive scientific and medical experience has demonstrated that fluoxetine [Prozac] is an effective antidepressant.

Wyeth said: "We recognise the need for both pharmacological and non-pharmacological treatments for depression."

On the new training for therapists, Mr Johnson said the programme signalled a decisive shift away from drugs in favour of non-drug treatments for depression. "We are not taking the decision away from clinicians," he said.

"For many, medication is successful. But talking therapies can have dramatic effects. We have put a lot of emphasis on medication in the past and it is about time we redressed the balance and put more emphasis on talking treatments."

The treatments that do work

* Exercise: Helps some people with depression.
Douglas Adams, author of The Hitchhiker's Guide to the Galaxy, said running helped him cope with depression.

* Friends: Talking through your feelings can help in mild depression with a friend or relative or in a self-help group.

* Cognitive behavioural therapy: Teaches you to challenge negative thoughts and feelings of hopelessness.

* Interpersonal therapy: Focuses on relationships and problems such as difficulties with communication.

* Counselling: Helps you think about the problems in your life and find new ways of dealing with them.

* Antidepressants: Increasingly seen as a second-line treatment, if exercise or talking treatments do not work.

[Al-khiyal]

The vested interests that conspire to bury bad news

February 26, 2008 -- "Publication bias" is not a phrase widely familiar to people outside the world of academic research. Yet it can explain how a drug launched as a safe and effective treatment can later turn out to be useless, or even deadly.

Pharmaceutical companies invest millions of pounds in drug research and have a powerful commercial interest in publishing positive findings for the medicines they have spent years developing. But they are equally keen to keep quiet about those trials which show no effect.

Medical journals comply in this process of self-censorship because, like the lay media, they are competing for readers and positive results – the more dramatic the better – attract more attention. The result is that over months and years, an impression is created that a drug is more effective, and has fewer side-effects, than is really the case.

This is known as "publication bias", the selection of only positive studies for publication. If all the studies conducted, positive and negative, were reviewed the overall impression might be very different. Publication bias has been blamed for the debacle over the powerful painkiller Vioxx, dramatically withdrawn from the market in 2004, after it was suspected of causing heart attacks. The fatal side-effect had not been picked up despite years of research in thousands of patients. Now it is being blamed for the revelation that two decades after their launch, the new-generation anti-depressants, including Prozac and Seroxat, may be no better than placebos.

Data obtained from the Food and Drug Administration in the United States under freedom of information legislation showed that when all the trials, published and unpublished, submitted at the time the drugs were licensed were analysed, it showed no clinically significant effect. The finding makes the review of the present Nice guidelines on the treatment of depression "all the more urgent", according to Tim Kendall, the head of group responsible for drawing them up.

The present guidelines, issued in 2004, recommend psychological treatments be offered as an alternative to drugs, especially in mild depression, a change from the original guidelines which recommended drugs as the first line of treatment. Revised guidelines are due at the end of the year.

Dr Kendall, a consultant psychiatrist in Sheffield, said: "The doubt the study raises is how much confidence we can have in our current data set, which is much bigger [than in the study] but may not be complete. The drug industry says they are being much more open but I am not convinced we are seeing the data we should see, and we are certainly not seeing what the licensing authorities are seeing."

[Bent_Bladi]

first viagra, now this... lol - poor pharmaceutical companies

[Al-khiyal]

Prozac, used by 40 million people, does not work say scientists

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Negative antidepressant studies routinely buried, research shows

February 25, 2008 -- According to a recently published article in the New England Journal of Medicine (NEJM), 'Selective publication of antidepressant trials and its influence on apparent efficacy', studies showing antidepressants to be effective are published more often than those reporting negative outcomes, and the results of negative studies are often skewed to appear positive.

The authors of the NEJM article - led by former FDA medical reviewer Dr. Erick H. Turner - obtained 74 FDA-reviewed studies of 12 commonly prescribed antidepressants. Of these studies, 37 reported positive results and 37 reported negative results. Upon review, the researchers found that while only one of the 37 positive studies escaped publication, a full 22 of the 37 negative studies never saw print. Even more astounding was the fact that of the 15 published negative studies, 11 of them were spun by the publishing journal in a way that, according to Dr. Turner and his team, conveyed a positive outcome.

More precisely, the journal articles covering these studies cleverly highlighted secondary positive results as if they were the primary outcomes that the studies hoped to attain. As if that still weren't enough, nine of these 11 studies completely omitted the disappointing primary outcome in lieu of a positive secondary outcome. The exact reasons for lack of publication are unclear.

Commenting on the results of the article Dr. Jeffrey M. Drazen, editor in chief of The New England Journal remarked that "We need to show respect for the people who enter a trial. They take some risk to be in the trial, and then the drug company hides the data? That kind of thing gets us pretty passionate about this issue."

While this is not the first time the effectiveness of antidepressants has come under scrutiny, this article marks the most thorough analysis of the clinical evidence to date.

Up to this point published studies showed that about 60% of study participants find relief from depression using antidepressants, compared with 40% of those given a placebo. When this unpublished data is entered into the equation, however, the NEJM report concludes that antidepressants outperform placebo by a much more modest margin.

Currently, published literature suggests that 94% of antidepressant studies ended positively. This number plummets to only about half when unpublished studies are included, however, with antidepressants only narrowly outperforming placebo overall.

Dr. Turner said of his findings that "the bottom line for people considering an antidepressant, I think, is that they should be more circumspect about taking it, and not be so shocked if it doesn't work the first time and think something's wrong with them." He went on to say of doctors that "they end up asking, 'how come these drugs seem to work so well in all these studies, and I'm not getting that response?'"

[Al-khiyal]

Pharming today