I have steadily endeavored to keep my mind free so as to give up any hypothesis, however much beloved (and I cannot resist forming one on every subject), as soon as the facts are shown to be opposed to it.
— Charles R. Darwin
I’m getting old: 50, almost 51, and that’s over 350 in dog years. As a result of my advancing age there are things I do not get: tattoo’s, hip hop, visible undergarments, and those rectangular, square plastic glasses that seem so popular and look hideous on everyone. It gets harder to change.
I have been able to stick MD after my name for almost a quarter century now (175 dog years for those keeping track), and it does give a sense of perspective to the ebb and flow of medical therapies. Medicine for the last hundred years has been all about change. Dogma from last century is nonsense this century, all due to that damn science. It gets so tiresome having to learn something new.
Last month’s New England Journal of Medicine was another in a seemingly endless series of plus ça change, plus c’est la même chose moments.4 They published the results of the CORTICUS study, a trial that looked at Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration, was conducted by Irving Kirsch and colleagues, who reviewed clinical trials of six antidepressants (fluoxetine, venlafaxine, nefazodone, paroxetine, sertraline, and citalopram). They looked at all studies submitted to the FDA prior to approval, whether published or unpublished. They found:
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.
The press has largely reported this study as showing that “antidepressants don’t work” but the full story is more complex. This analysis certainly has important implications for how we should view the body of evidence for these antidepressants. It also illuminates the possible role of publication bias in the body of scientific literature – something that has far ranging implications for science-based medicine.