Mad World

The study, a meta-analysis of published and unpublished trials into the effectiveness of the modern SSRI drugs, such as Prozac, found they only outperformed a placebo in people with the most severe depression.

But even then the researchers concluded that they only outperformed a placebo because people with the most severe depression were less responsive to the placebo effect, rather than more responsive to the drugs.

The drug companies have come out and disagreed with the findings, but it seems that science is not on their side.

Disturbing findings

Marjorie Wallace, of mental health charity Sane, has been quoted as saying the findings of the research are "very disturbing" as SSRIs were seen as "the great hope for the future".

I would agree that the findings are disturbing because it appears that as a society we have embraced something that seemed like a perfect quick fix which has turned out to be more akin to an illusion.

But I hope the eventual consequences could be more positive if it leads us to tackle depression in terms of its real societal causes rather than its chemical symptoms.

This latest study follows on from research published last month in the New England Journal of Medicine, which I discuss in a feature to be published in Community Care magazine next month.

Here is an excerpt from that feature:

New England research

"The research compared all the antidepressant trials registered with the US Food and Drug Administration with those that actually made it to publication in a medical journal. Of the 74 registered antidepressant studies analysed, 38 gave a positive outcome. All but one of them were published.

The remaining 36 studies returned either negative or questionable results for the drugs. Of these, 33 were not published or were published in a way which suggested their findings had been positive.

The result of this selective reporting is significant. While in reality 51% of the antidepressant trials had a positive outcome, any researcher, doctor or member of the public studying the published research would get the impression that 94% of the trials had been positive. Policy makers from around the world rely on the same published data to make their decisions.

Risk-benefit ratio

The researchers did not investigate the reasons for non-publication, which may be based on a failure to submit manuscripts or decisions by journal editors not to publish. And they point out that each drug was still shown to be superior to placebo.

But they add: “On the other hand, the true magnitude of each drug’s superiority to placebo was less than a diligent literature review would indicate.”

“By altering the apparent risk-benefit ratio of drugs, selective publication can lead doctors to make inappropriate prescribing decisions that may not be in the best interest of their patients and, thus, the public health.”

Tim Kendall, psychiatrist and deputy director of the Royal College of Psychiatrists’ research and training unit was not surprised by the results. He found similar evidence of selective reporting when he studied the use of antidepressants for children in 2004. When the selective publishing was countered and all the research was made available to a group of professionals assembled for the study they decided they would only prescribe one of the six drugs tested. Previously they had been happy to prescribe all of them.

Side effects

Risk-benefit calculations are not just an academic exercise, as antidepressants can have potentially severe side effects for some. The National Institute for Health and Clinical Excellence (NICE) now only recommends one antidepressant for children after the others were linked to suicidal behaviour. Even that should only be offered in serious cases and used alongside talking treatments, the guidelines say.

And Kendall believes there is no reason why 18 should be a cut off in terms of people experiencing suicidal thoughts and suggests the effect probably applies until someone is 30.

Chemical imbalance theory

One of the problems many opponents have with antidepressants is the explanation used by the drugs industry for how they work. Serotonin Specific Re-uptake Inhibitors (SSRIs), the type of antidepressants introduced in the 1990s and including drugs such as Prozac, ensure serotonin, which has been linked with mood, stays in the brain longer.

Joanna Moncrieff, psychiatrist and senior lecturer at University College London, argues that evidence on the role of serotonin is “contradictory and inconclusive” but that has not stopped the pharmaceutical industry from promoting the so-called “chemical imbalance theory”. The theory goes that depression is caused by a serotonin imbalance in the brain, which antidepressants can correct. But it has never been proved.

US researchers Jeffrey Lacasse and Jonathan Leo writing in the Public Library of Science medical journal in November 2005 argued that the claimed efficacy of SSRIs was often cited as indirect support for the serotonin hypothesis. Yet this backward reasoning, they argue, is like saying that because aspirin cures headaches, then headaches must be due to low levels of aspirin in the brain."

The feature will be published in full in the the March 13 issue of Community Care
The Royal College of Psychiatrists urges people not to stop taking antidepressants without speaking to their GP