“In Defense of Antidepressants.”
Okay, before we start, here’s an extract from my lead mcmanweb article on antidepressants:
The strongest scientific evidence we have is not how well antidepressants work, but how badly they perform and how harmful they may be to certain individuals. Here's the low-down:
Two meta-analyses of the FDA clinical trials conducted by Irving Kirsch of the University of Connecticut in the late 1990s-early 2000s of Pharma-sponsored clinical trials - including ones not published - in the FDA database found that antidepressants worked only marginally better against depression than placebos. There have been a number of expert rebuttals to these findings, but no actual study to contradict Kirsch.
The article reports on the most authoritative real-world study on antidepressants, the NIMH-underwritten STAR*D from the mid-2000s. We continue from my article:
Commenting on STAR*D, in a 2009 blog, Nassir Ghaemi MD of Tufts University noted that:
“Even if antidepressants worked in the short term (2 months, which is also what the meta-analysis assessed), one-half of patients who stayed on them relapsed into depression within one year. At the one year outcome, only about 25% of patients actually had remained well on and tolerated an antidepressant, much below the levels most clinicians seem to feel occurs in their clinical experience.”
One in four! According to the best data we have, just one in four individuals treated with an antidepressant get well and stay well. And this was in the best possible care setting. Is your clinician aware of this? Probably not.
Neither is Peter Kramer of Brown University. Dr Kramer is the author of the 1993 “Listening to Prozac,” which is largely a product of the time, back when we all trusted Pharma a lot more than we do now. We have learned a lot since then, including the fact that these drugs can be highly destabilizing to individuals with bipolar and with depressions that cycle like bipolar.
But Dr Kramer in his NY Times article mentions neither STAR*D nor the obvious risks of taking an antidepressant. Huh?
Dr Kramer’s defense of antidepressants is specious and drearily unoriginal, one based on a speculative nitpicking of Kirsh. Back in a newsletter piece I did nine years ago, I referred to this as the “Van Meegeren Defense.”
Prior to World War II, Han Van Meegeren earned a nice living for himself selling bad forgeries of Vermeers. When World War II came along, one of Van Meegeren’s customers turned out to Reichsmarshall Hermann Goring. After the War, Van Meegeren was arrested for collaborating with the Nazis and charged with treason.
Here’s the part of the story I love: Van Meegeren’s defense to selling cultural treasures to the Nazis was that they were not real Vermeers, but his own forgeries. In other words, he had to convince the court that he had cheated.
Okay, now that you “get” the Van Meegeren Defense, here is what Dr Kramer has to say in his NY Times article:
Consequently, companies rushing to get medications to market have had an incentive to run quick, sloppy trials.
In other words, to cheat. What Dr Kramer is saying is that clinical antidepressants trials sponsored by drug companies might have yielded better results had they stuck to protocol and included only patients most likely to respond to antidepressants, namely those with severe depression. In effect, the drug companies, in their haste to recruit patients, probably included a substantial number of likely non-responders, namely those with milder forms of depression or those who plain lied to get into a trial. Thus, according to Kramer:
Often subjects who don’t really have depression are included — and (no surprise) weeks down the road they are not depressed. People may exaggerate their symptoms to get free care or incentive payments offered in trials. Other, perfectly honest subjects participate when they are at their worst and then spontaneously return to their usual, lower, level of depression.
As I stated earlier, this is not a new explanation. I first came across it soon after Kirsch’s second meta-analysis was published in 2002. Basically, academic critics acknowledged that Kirsch had made a bullet-proof case based on the evidence. So, then, how to explain the evidence?
Ah, the Van Meegeren Defense. In other words, if the drug companies had not cheated to begin with, maybe, just maybe, the results might - just might - have come out more in their favor.
It’s all speculation, of course. The only real way to counter Kirsh’s bullet-proof evidence is with bullet-proof evidence of one’s own. And while we're at it, to come up with an authoritative real-world study to counter the STAR*D real-world study.
There are many nuances to the antidepressant debate, and in all likelihood these meds work for a certain subpopulation of depressed patients (if we only knew who they were), but - again - this is speculation, not science.
The bottom line is the most convincing evidence we have on the (non)efficacy of antidepressants comes from Kirsch and STAR*D. The only counter-evidence is recycled speculation, Kramer-style.
Robert Whitaker on his Mad in America blog picks Kramer apart in far greater detail, concluding with:
On Sunday, in this essay "In Defense of Antidepressants," the American public has been treated to yet another dose of misinformation.