Hard News by Russell Brown


The drugs don't (always) work

The reporting of medical research is a tricky business: the dynamics of news are often unkind to a measured assessment of what is actually being reported. So it might help to know that the study on the effectiveness of SSRI-type anti-depressants that leads the Herald this morning is not as new as its currency in the headlines would suggest.

The research is a meta-analysis of 47 clinical trials presented to the US FDA before approval of Prozac and other drugs. The data were obtained under America's Freedom of Information Act, and include both published and unpublished trials. This has the effect of removing "publication bias": where only the published research is examined.

Irving Kirsch, the leader of the project, published findings on this group of trials in 1998 and again in 2002, when he was at the University of Connecticut (he is now at the University of Hull in Britain). In large part, what is being reported is not new, and has been the subject of debate over the efficacy of SSRIs for years.

What is new, as explained in this editorial summary in PLoS Medicine, the online journal that has published the analysis, is that Kirsch et al have set out to determine the role of "initial severity" in the efficacy of SSRIs versus placebo.

Kirsch's previous analyses of the same trials had already raised doubts about the efficacy of SSRIs, so that was a given in the new study. So what did it find? It found there was virtually no difference between drug and placebo for patients with mild depression, but the efficacy of SSRIs rose relative to placebo as the initial severity of the depression being treated rose:

The difference in improvement between the antidepressant and placebo reached clinical significance, however, in patients with initial HRSD scores of more than 28—that is, in the most severely depressed patients. Additional analyses indicated that the apparent clinical effectiveness of the antidepressants among these most severely depressed patients reflected a decreased responsiveness to placebo rather than an increased responsiveness to antidepressants.

It did not say the drugs don't work.

It did find that other ways of treating depression -- including a therapy as simple as increased exercise -- may be just as good as treatment with SSRIs for many patients. It raises questions about the direct-to-consumer advertising of these drugs to people who may not need them.

Again: this is an ongoing study of the same body of data by the same researcher. It does not include trials presented to regulatory bodies elsewhere in the world, nor any conducted since the approval of Prozac and other drugs by the FDA. And as senior psychiatrist Dr Allen Fraser points out in the Herald's lead story this morning (yes, the one headed ' Anti-depression drugs don't work - study'), real-world SSRI treatments are not necessarily well represented in the results:

Less than 10 per cent of patients were deemed suitable for trials, and the trials lasted less than six weeks.

Treatment for depression usually lasted at least six months, and patients generally showed steady improvements throughout that time.

"I think that when [antidepressants] are used for people with a significant depression, these medications are essential," Dr Fraser said. "They are not just good, they are essential."

But there were valid grounds for suggesting that less severely depressed people have non-medicated treatment initially.

The danger here is that people taking these drugs will see only the headlines (and Radio New Zealand seems to have been about little else this morning) and just stop taking the tablets. I can't emphasise enough how dangerous this could be.

No Right Turn has already slapped up a post declaring SSRIs to be "snake oil". There are important implications about the conduct of drug companies, in their selectiveness as to what research they publish, and how they advertise their products. These are not lollies. But anyone minded to shout "snake oil" needs to calm down. To, metaphorically speaking, take a chill pill.

They could also read this interesting discussion of the way the news media handle this debate (it summarises the work of Kirsch and several other researchers who are strongly critical of him), and take its concluding paragraphs to heart:

Therefore, contra some of the media "hype" on this topic, antidepressant research confirms an empirically demonstrated drug-placebo difference, although careful examination of this literature reveals that this difference is not nearly as large as most individuals believe, or as many of the pharmaceutical companies would have the public believe.

Currently, the methodological problems with antidepressant trials preclude us from concluding definitively that the difference actually indicates specific biological effects of the drugs, as various nonspecific factors have not been adequately ruled out. Until these questions are answered, the media should understand that placebos can be double-edged swords, and that "expectancy" effects can result in harm as well as benefit.

In a piece on this topic for the Guardian, a UK newspaper, Jerome Burne (2002) reports that many subjects in Leuchter's trial (2002) relapsed and requested to be placed on the active medication after learning they were in the placebo arm. Vedantam's Washington Post piece is similar to other articles on this topic that have appeared in the popular press recently, in that it occasionally betrays an imbalanced presentation of the evidence. The media should continue to follow this complicated debate and report on it responsibly, making certain not to overhype the "power" of placebo and, as a consequence, the "powerlessness" of antidepressants.

Meanwhile, on another tip entirely, I'll be among those speaking (I expect my turn, on behalf of our forthcoming show, Media7, to be quite brief) at public briefings on TVNZ 7 in Auckland and Wellington tomorrow. There will be clips from new shows, speeches and some food and drink. The details are:


The Academy Cinema,
Auckland Central Library Building,
44 Lorne St,
Auckland City
Starts: 10:30am


Faculty of Law, Level One, Lecture Theatre 4,
Victoria University of Wellington,
Government Buildings,
15 Lambton Quay,
Starts: 5:30pm

You're most welcome to come along. I gather it would help a lot if you could email TVNZ7@tvnz.co.nz and put in the subject title either: Yes Auckland or Yes Wellington, to indicate in which location you will be attending.

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