Ben Goldacre

The Guardian,

Saturday January 26 2008

If there’s one thing I love, it’s academics who take on the work of investigative journalism, because they are dogged. This has been a bad week for the SSRI antidepressants.

First there’s the stuff you already know: bad data got buried. In a cracking new analysis of the “publication bias” in the literature, a group of academics this week published a paper in the New England Journal of Medicine which listed all the trials on SSRIs that had ever been formally registered with the FDA, and then went to look for the same trials in the academic literature.

37 studies were assessed by the FDA as positive, and with one exception, every single one of those positive trials got properly written up and published. Meanwhile, 22 studies that had negative or iffy results were simply not published at all, and 11 were written up and published in a way that described them as having a positive outcome. You’re a sophisticated reader, so you understand this doesn’t mean that they’re necessarily rubbish drugs, but you also understand that this is dodgy behaviour, all the same.

That’s the easy bit.

The second paper is more interesting. Over the past few decades, we have been subjected to a relentless medicalisation of everyday life by people who want to sell us sciencey solutions. Chancers from the $56 billion international food supplement industry want you to believe that intelligence needs fish oil, and that obesity is just your body’s way of crying out for chromium pills (“to help balance sugar metabolism” etc).

Similarly, quacks from the $600 billion pharma industry sell the idea that depression is caused by low serotonin levels in the brain and so – therefore – you need drugs which raise the serotonin levels in your brain: you need SSRI antidepressants, which are “selective serotonin reuptake inhibitors”.

That’s the serotonin hypothesis. It was always shaky, and the evidence now is hugely contradictory. I’m not giving that lecture here, but as a brief illustration, there is a drug called tianeptine – a selective serotonin reuptake enhancer, not an inhibitor – and yet research shows this drug is a pretty effective treatment for depression too.

Meanwhile in popular culture the depression/serotonin theory is proven and absolute, because it was never about research, or theory, it was about marketing, and journalists who pride themselves on never pushing pills or the hegemony will still blindly push the model until the cows come home. Which brings us on to our second new study on antidepressants. Two academics, a lecturer and an associate professor of neuroanatomy, decided to chase journalists, in the style of this column – or rather, in the style of this column on crack – and fired off multiple emails, demanding unrealistic levels of referencing from doubtless irritated and baffled hacks. They proudly document their work with an excessive number of examples, and I will pick just a few.

“In the New York Times (12/31/06), Michael Kimmelman wrote about the life and work of Joseph Schildkraut, one of the founders of the chemical theory of depression. The Times reporter stated, ‘A groundbreaking paper that he published in 1965 suggested that naturally-occurring chemical imbalances in the brain must account for mood swings, which pharmaceuticals could correct, a hypothesis that proved to be right [italics added].'” The prof’s gave chase. “E-mails to the author requesting a citation to support his statement went unanswered.” A victory for the noble pedantry.

“In another New York Times article (6/19/07), ‘On the Horizon, Personalized Depression Drugs,’ Richard Friedman, the chairman of Psychopharmacology at the Weill Cornell Medical College, stated: ‘For example, some depressed patients who have abnormally low levels of serotonin respond to SSRIs, which relieve depression, in part, by flooding the brain with serotonin.'” They chased, and they give no quarter. “For his evidence he supplied a 2000 paper by Nestler titled, “Neurobiology of Depression,” which focuses on the hypothalamic pituitary system, but not on serotonin.”

The serotonin hypothesis will always be a winner in popular culture, even when it has flailed in academia, because it speaks to us of a simple, abrogating explanation, and plays into our notions of a crudely dualistic world where there can only be weak people, or uncontrollable, external, molecular pressures. As they said in the Pittsburgh Tribune Review (4/2/07) “It’s not a personal deficit, but something that needs to be looked at as a chemical imbalance.”

The real world is more complicated than this simple dichotomy. But when you probe the evidence for simple fables about serotonin stories in popular culture, you’ll find “the quote was attributed to a psychiatric nurse practitioner, the author did not respond to e-mails, and the nurse’s e-mail was not available”.

References:

Here is the NEJM paper on the missing SSRI trials.

content.nejm.org/cgi/content/abstract/358/3/252

Here is “The media and the chemical imbalance theory of depression”

www.springerlink.com/content/u37j12152n826q60/

You can read an older Leo and Lacasse paper for free here if you haven’t got an academic login (it’s ridiculous that this stuff is behind a paywall).

Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature. Lacasse and Leo 2005.

The relative ropeyness of the serotonin hypothesis is nicely reviewed in this paper from Nature Reviews Neuroscience

www.nature.com/nrn/journal/v6/n3/full/nrn1629.html

Contemptibly that is behind a paywall too but there is a lay summary from my chums MindHacks here

www.mindhacks.com/blog/2005/05/is_depression_a_brai.html

And if this sort of thing interests you, then you can listen to a looong lecture from me about medicalisation called “more than molecules”, at the British Pharmacology Society meeting last year, here.

www.badscience.net/?p=602