The antidepressant debate

By Felix Salmon
July 11, 2011
big essay by Peter Kramer, the author of Listening to Prozac.

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The NYT’s new-look Sunday Review led this weekend with a big essay by Peter Kramer, the author of Listening to Prozac. But for all its length and detail, it’s very hard to read — at many points, doing so feels like listening to one half of a telephone conversation. Which makes sense when you consider Kramer’s opening paragraphs:

In terms of perception, these are hard times for antidepressants. A number of articles have suggested that the drugs are no more effective than placebos.

Last month brought an especially high-profile debunking. In an essay in The New York Review of Books, Marcia Angell, former editor in chief of The New England Journal of Medicine, favorably entertained the premise that “psychoactive drugs are useless.” Earlier, a USA Today piece about a study done by the psychologist Robert DeRubeis had the headline, “Antidepressant lift may be all in your head,” and shortly after, a Newsweek cover piece discussed research by the psychologist Irving Kirsch arguing that the drugs were no more effective than a placebo.

I’ve included, here, all of the links that Kramer provides. Which is exactly one, to the NYT topic page on antidepressants. If you want to find Angell’s article, or the USA Today piece, or the Newsweek cover story, you’re on your own: Kramer and the NYT won’t help you. And Kramer, clinical professor of psychiatry at Brown University, takes care not to even mention part two of Angell’s two-part series, where she talks at length about how psychiatry has been captured by drug companies, who “are particularly eager to win over faculty psychiatrists at prestigious academic medical centers”. (After reading Angell’s second essay, you’ll certainly wonder why Kramer doesn’t disclose how much income he gets from pharmaceutical companies.)

In any case, if you read Kramer’s piece and wondered what on earth he was talking about, then I would highly recommend you now read Angell, both part 1 and part 2. In general, the NYRB is a bit harder to read than the NYT, but not in this case — Angell’s essays are models of clear and powerful empirically-based argument, while Kramer’s looks positively messy and incoherent in comparison.

Here, for instance, is Angell:

For obvious reasons, drug companies make very sure that their positive studies are published in medical journals and doctors know about them, while the negative ones often languish unseen within the FDA, which regards them as proprietary and therefore confidential. This practice greatly biases the medical literature, medical education, and treatment decisions.

And here’s Kramer:

Not long ago, I received disturbing news: a friend had had a stroke that paralyzed the right side of his body. Hoping to be of use, I searched the Web for a study I vaguely remembered. There it was: a group in France had worked with more than 100 people with the kind of stroke that affected my friend. Along with physiotherapy, half received Prozac, and half a placebo. Members of the Prozac group recovered more of their mobility…

Surprised that my friend had not been offered a highly effective treatment, I phoned Robert G. Robinson at the University of Iowa’s department of psychiatry, a leading researcher in this field.

Kramer knows Angell’s argument, of course — his essay is a direct response to hers. Yet he still feels comfortable cherry-picking a single obscure French study — which, again, he doesn’t link to — in order to prove that Prozac is “highly effective” in stroke victims. I would love to know what Kramer thinks of this xkcd strip; for all that Kramer complains about “the news media’s uncritical embrace of debunking studies”, the fact is that it’s the outlier studies that never get replicated which tend to get the most press.

Angell’s main argument, expounded at book length by Irving Kirsch, is that antidepressants are, amazingly, even worse than placebos; the main evidence for this is a massive database of FDA trials, which was obtained by Kirsch and his colleagues via the Freedom of Information Act. Kramer’s response to this is to say that the FDA trials are flawed, and that some large number of the subjects weren’t depressed at all.

Or, to put it another way, lots of people were diagnosed with depression and put onto a trial of antidepressant drugs, even when they were perfectly healthy. Which sounds very much like the kind of thing that Angell is complaining about: the way in which, for instance, the number of children so disabled by mental disorders that they qualify for Supplemental Security Income (SSI) or Social Security Disability Insurance (SSDI) was 35 times higher in 2007 than it was in 1987.

And it’s getting worse: the editors of DSM-V, to be published in 2013, have written that “in primary care settings, approximately 30 percent to 50 percent of patients have prominent mental health symptoms or identifiable mental disorders, which have significant adverse consequences if left untreated.”

Those who would defend psychopharmacology, then, seem to want to have their cake and eat it: on the one hand it seems that serious mental health disorders have reached pandemic proportions, but on the other hand we’re told that a lot of people diagnosed with those disorders never really had them in the first place.

To a first approximation, I know nothing at all about psychiatry, psychopharmacology or the optimal treatment of depression. But as a lay reader with a decent understanding of statistics and as someone whose sister is one of those very rare people whose PhD was a negative thesis, I can tell you that Angell’s articles are vastly more compelling than Kramer’s attempt at a rebuttal.

Does that mean I now believe that antidepressants do no good at all? No — as a good Bayesian, I’m not going to let a single article do that. But I was looking forward to a strong response to Angell. And the weakness of Kramer’s essay only serves to confirm my suspicions that Angell and the anti-antidepressant crowd really are onto something.

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