Lots of attention has been paid to the latest review/meta-analysis demonstrating that popular antidepressant medications don't seem to be that much more effective than placebos. While this certainly isn't the first time someone has demonstrated that Prozac is only mildly more useful than a sugar pill (unless, that is, you fall into the "severely depressed" category), this review was noteworthy because it consisted mainly of previously unpublished studies done by the drug makers before the drugs were put on sale. As Time magazine notes, this allows the researchers to "avoid a bias that often plagues reviews of previous research: the tendency for conclusive positive results to be published, sometimes more than once, and thus over-represented, while mediocre results can be ignored or even swept under the rug."
That said, the study does come with one big caveat: the trials it analyzed are all 6-8 weeks long. In that short time frame, Prozac is often no better than a placebo. (Keep in mind that SSRI's rarely produce any positive benefits for the first several weeks, a phenomenon known as the Prozac lag.) However, the performance gap between placebos and SSRI's tends to widen the longer a person is taking the drug. After a while, the placebo effect tends to wear off, which is why people on an "active drug" are less likely to relapse.
And then there's the meta problem of meta-analyses like this. If a large percentage of the SSRI benefit comes from the placebo effect - people expect the drug to work, and so it works - then learning that Prozac isn't actually that effective might actually make it less effective. It's long been recognized that both placebo response and drug response for antidepressants have steadily increased over time. Much of this increase is most likely due to marketing. People have been trained by Eli Lilly's ads to believe that a little blue pill will make them less depressed, and so they end up significantly less depressed. A little self-delusion might not be such a bad thing after all.*
*Obviously, it's important to know that our drugs aren't that much more effective than a sugar pill. Studies like this are extremely important. But it's also worth remembering that the placebo effect also produces real changes in the brain, which have real therapeutic benefits.
Brain & Behavior
Comments (5)
Peter Kramer wrote a piece about this. Basically you can't lump all the trials together, because some aren't constructed well enough to distinguish the drug from the placebo.
http://www.slate.com/id/2182585
"In the rush to bring patented compounds to market, pharmaceutical houses sometimes enroll research subjects who barely meet criteria for the condition under study (in this case, depression). In some early trials, researchers may purposely use low doses; the idea is to squeak by the FDA's minimum efficacy requirements without raising concerns about side effects. Because the subjects do not have the relevant disease, and because normal people's moods wax and wane, these sloppy studies have high placebo response rates.
"And then the research tends not to get published, because it's simply not credible. Or the consequence is worse yet. Every researcher in the field can name a promising substance that was lost for patient use as a result of poor study design or overeager recruitment of subjects, resulting in astronomical placebo response rates."
Posted by: Mike | February 27, 2008 3:23 PM