Placebo Nation: The antidepressant controversy

Another study purports to find that, for most people, Prozac and the other members of the antidepressant family of pharmaceuticals are no better than sugar pills. Expect Big Pharma to object, but not too loudly. At least, don't expect them to expend too much effort and money denouncing the findings. We've heard this before, and it would seem that neither patients nor the doctors that prescribe antidepressants care much about whether or not the drugs actually do what their makers claim they do.

You can go all the way back to 1998 to find studies casting doubt on the efficacy of antidepressants. Here's a summary in New Scientist of a meta-analysis published that year:

...the drugs were only 25 per cent more effective. In addition, they suggest that even that 25 per cent could be due to an additional placebo effect derived from the side effects caused by the antidepressants, which alerted patients to the fact that they were receiving an active drug rather than a placebo

The new report, another meta-analysis of previous studies, including those that were never published, concludes that only in the most severely depressed patients did the drugs actually improve mood, and even then we're not talking about much of an improvement.

Drug-placebo differences increased as a function of initial severity, rising from virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very severe depression, reaching conventional criteria for clinical significance only for patients at the upper end of the very severely depressed category.

...

Drug-placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication.

One might argue that both the study referred to in New Scientist, which appeared in Prevention & Treatment, and the new one, published this week in PLoS Medicine, were led by the same researcher, one Irving Kirsch of the University of Hull in the U.K.

But he's not the only one coming up with dispiriting results. His new paper is co-authored by half a dozen American and Canadian scientists. And, more importantly, "the authors received no specific funding for this study." In fact, Kirsch has worked as a consultant for Squibb and Pfizer, two of the world's leading manufacturers of drugs, including those about which his team is casting such depressing aspersions. Squibb, for example, makes Serzone (nefazodone).

Furthermore, the new study takes care of publication bias, which tends to favor studies that find a positive outcome for a drug. We all know what happens to most studies with a negative conclusion. This has impressed news editors. One day after publication, the study is all over the science sections. The Sydney Morning Herald's lead, for example is "Millions of people taking commonly prescribed antidepressants could be wasting their time and money, research suggests."

But will the drug makers (or their shareholders) lose much sleep over this apparent blow to their big money-makers? Probably not. First of all, it's hard to underestimate the power of the placebo effect. When people feel like a pill is changing their metabolism or physiology ;;;;; because it actually is ;;;;; they don't much care that the effect has nothing to do with the selective serotonic uptake that the drug is supposed to inhibit. And so they feel better.

Many doctors know this and despite their skepticism prescribe Prozac or Seroxat for the same reason. Placebos can work. And it's not only doctors dealing with moody patients. Sports medicine has figured this out. In a recent study in The Journal of Neuroscience (27(44):11934-11939), researchers found that

After repeated administrations of morphine in the precompetition training phase, its replacement with a placebo on the day of competition induced an opioid-mediated increase of pain endurance and physical performance, although no illegal drug was administered.

There are ethical questions in both situations. But for me the most interesting question is, how much effort should be put into spreading the word that Prozac et al, aren't any better than placebos?

It's important because many of us here at ScienceBlogs like to point out that most "alternative" medicines are basically placebos masquerading as the genuine article. Lots of traditional Chinese medicines fall into that category, and yet literally billions of people turn first to powdered seahorse or tiger bones because that's what they know best. So in the interests of avoiding hypocrisy, we in the Enlightened West should be just as willing to draw attention to the failings of conventional drugs, no?

In fact, the only difference I see between bogus traditional Chinese medicine and many products of Big Pharma, is the former are often made from endangered species ;;;;; the more threatened the better. By contrast, the only "harm" associated with prescribing conventional placebos may be restricted to our collective trust in Big Pharma. Although that's hardly a bad thing.

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