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The Antidepressant Controversy:  a Different Perspective

A 2008 study [1] concluded that the use of antidepressant drugs for severely-depressed patients was more efficacious than placebo in reducing symptoms of depression.  Controversially, it also found that the antidepressants studied did not decrease the suffering of mildly and moderately-depressed patients more than patients dosed with placebo.  While these findings have been met with both interest and disbelief, it is important to point out that the results are hardly new- Prozac was previously claimed to be no better than placebo in all but very depressed patients ; in fact, the major author of the 2008 study (Kirsch) published a study with exactly the same results in 1998 [2].  The widely-publicized point of the current JAMA study is that antidepressants should be reserved for all but the very depressed.  It is also suggested that the patients who responded or remitted on placebo did so because they thought the pills would work, it was “all in their heads”. A more recent article discusses the subject further [3].

This is a typical, but especially dizzying example of misunderstanding when it comes to scientific experimental design and interpretation.  In many previous studies, antidepressants and placebos have worked for all patients dosed, independent of their level of depression, at a response rate of about 30-50%.  The conclusion is that since antidepressants aren’t more therapeutically efficient than placebo, they aren’t worth taking.  Let’s reframe this experiment for some perspective: suppose you were depressed and your doctor offered you one of two equally-effective medications, “A” or “B”.  Suppose your pharmacist is out of medication “A”, but he does have medication “B”.  Reason would dictate choosing medication “B”-and suppose you respond to medication “B”.  You are then told that medication “B” was a placebo capsule.  But now to the scientific issues: notice that the real question is not why medication “A” would have only worked as well as “B” (since “A” was not involved in dosing at all)-the real question is why “B” worked at all.  Studies that show that antidepressants don’t work better than placebo could better be summarized by the authors: “the mechanism by which antidepressants cause response or remission in a depressed patients is hypothesized, but scientifically unknown; the mechanism by which placebo medications causes response or remission in depressed patients is also hypothesized, but scientifically unknown.  In our study, the percentage of patients who responded or remitted were approximately the same in the drug-dosed and placebo-dosed groups, within the rather large imprecision that characterizes any such  in vivo study”.  This proposed summary removes the unwarranted inference that dosing with an antidepressant is no better than dosing with nothing at all and points the science to the real enigma: why do placebos work at all?

The next misunderstanding of the scientific process is the suggestion that the reason that the placebo group responded was because they believed the medication would work, in the vernacular, “it was all in their heads”.  Notice that such a statement is neither a scientific statement-or even a reason, as the term “reason” is commonly used.  The “all in their heads” argument fails to be a scientific statement because it cannot be either proved or disproved: we have no access to what is “in people’s heads”-we are rather setting up a circular argument: if the person responds to a placebo, they must have believed it was going to work, even if they tell us their belief was quite the contrary.  The “all in their heads” arguments fails as a valid reason because it is too inclusive-no matter what the results are, the argument can be used equally effectively.  We don’t allow this extensive inclusivity in what we mean by “a reason”.  It is the logical equivalent of “it happened because of God’s will”-no matter what happens, the “reason” is the same.  The “all in the person’s head” argument is not a reason, it is a belief, and like all beliefs, different people can accept it or reject its validity.

In summary, scientific drug trials produce data which is straightforward to understand, but complex to translate to real-life decisions.  The current JAMA study reinforces our ignorance of the placebo effect, but does not, despite its claims, help the depressed patient decide whether antidepressant therapy is a worthwhile option.

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