The 60 Minutes segment featuring Irving Kirsch, on the placebo effect in antidepressant research, is causing some reactions. The American Psychiatric Association (APA) has posted a response on their web site. We imagine that many patients taking SSRIs for depression might be confused at this point, and are searching for clarification. To further clarify the scientific basis for their press release, we think the APA should at a bare minimum answer the following questions:
1) The APA quotes psychiatrist Jeffrey Lieberman who says that, “There is abundant evidence that supports the efficacy of antidepressants above and beyond the effects of placebo.” Would it be possible to list the abundant research you are referring to? Keep in mind that Dr. Kirsch also said that this is the case – but he pointed out that for most patients it is clinically insignificant. We assume that you are saying that there is research that shows there is a large difference.
2) Jeffrey Lieberman also states that Kirsch’s “conclusion is at odds with common clinical experience.” Isn’t the APA basically saying that we should discard 20 years of published, peer-reviewed research on antidepressants, and instead, trust the opinions of academic psychiatrists (many who have received substantial payments from the makers of SSRIs over the years)? How is this congruent with the standards of evidence-based medicine? This statement also seems to miss a basic point of Kirsch’s work which was not that people on SSRI’s don’t get better, but that people on placebo also get better- that antidepressants have only a tiny advantage over non-specific generalized helping. Over the past tweny years there has been a push towards evidence-based medicine, and clinical trials have been used to measure the true medication response. What was the purpose of these trials if we are going to discard them?
3) In regards to the FDA, the APA states that, “Kirsch’s conclusions were widely discredited by the FDA.” At first look, this seems totally untrue. Could you please mention the publication where this finding was made public? We are not aware of any, and even Thomas Laughren of the FDA said on 60 Minutes that the difference between medication and placebo is modest. Did he misspeak? Dr. Thase and Dr. Kendall also said it was a very small difference. Did they misspeak?
Kirsch has pursued this line of research since the late 1990s, so he was clearly the best choice to feature on 60 Minutes. But, several other scientists that have also confirmed Kirchs’s findings, such as Khan et al, Ioannadis et al. and Barbui et al. These are peer-reviewed publications in the scientific literature, using rigorous methodology. Are these authors wrong?
3) If the medications are only helping a small subset (Thase said 14%) of the people taking them, then a large number of the people taking the medication are not getting any benefit and are being put at risk for the side effects. All medications require informed consent, where a physician informs a patients of the risks and benefits of medication, as well as being well-informed of the alternatives (e.g., exercise, therapy, self-help strategies). What should patients be told about this?
4) But there is a simple way to move on from all of these arguments. You clearly disagree with Kirsch, stating that he is wrong about the difference between medication and placebo- but you don’t say what the true difference really is. In science, researchers simply don’t believe assertions of others without compelling scientific data to back it up. Putting Kirsch aside, would it be possible for the APA to simply state what they believe the medical literature shows is the true difference between medication and placebo (and to cite the evidence)?
To illustrate the example of the placebo effect and how these studies are conducted, take the second of two trials which was submitted to the FDA to get Prozac approved for children. On the prospectively defined primary outcome, 69% of the children had a beneficial response. Granted this seems like a signifcant number, however 53% of the children on placebo also improved, which leaves a very small difference between the two groups. In fact, it was non-significant. It was only by looking at other measures that clinical significance was found; on the patient- and parent-rated scales there was no advantage to Prozac, but on one of the clinician-rated scales there was a slight advantage to Prozac. Although Russell Katz of the FDA wrote, “one could argue that this post hoc choice of primary outcome is inappropriate,”the FDA accepted the post hoc change and approved Prozac for children in January 2003 (Center for Drug Evaluation and Research, 2002, p. 13). It was the only antidepressant that the FDA ever approved for use in childhood depression…
Perhaps the most frustrating part about the APA’s response is that they don’t talk about science or mention any scientific evidence, really. They simply quote experts who think Kirsch is wrong. Thankfully, 60 Minutes did not do this. The great thing about the 60 Minutes piece was that millions of people got a close look at the actual science behind these medications. Granted, what they saw is not pretty. But at this point, the cat is out of the bag. As much as the APA might dislike this information being disseminated, there is no going back now. And, in terms of informed consent, we think depressed patients deserve to know the facts about these issues- and to hear them from people who understand the science- not to hear reassurances from authorities, statements that we believe starkly contradict the scientific studies.