Newsweek has just weighed in with a cover story ("Antidepressants Don't Work") based on the recent JAMA antidepressant study and previous meta-analyses of FDA and drug-company data. Here and elsewhere, I have had my say on this research.
By way of further commentary, I want only to present a quibble. Midway through the Newsweek piece, in a critique of the monoamine theory of depression, the reporter writes: “And a new drug, tianeptine, which is sold in France and some other countries (but not the U.S.), turns out to be as effective as Prozac-like antidepressants that keep the synapses well supplied with serotonin. The mechanism of the new drug? It lowers brain levels of serotonin. ‘If depression can be equally affected by drugs that increase serotonin and by drugs that decrease it,’ says [Irving] Kirsch, ‘it's hard to imagine how the benefits can be due to their chemical activity.’”
A fact-checker would have had only to look at the Wiki on tianeptine to see that the drug dates back to the 1980s. So much for “new.” For decades, then , tianeptine, which at a gross level enhances serotonin re-uptake, was presented as a counterexample to prevailing theories; looking at old files, I see that I discussed the case of tianeptine in public lectures dating back to the mid-1990s. But recent evidence suggests that tianeptine actually increases serotonin levels regionally, for instance, in an area of the hippocampus thought to be related to mood regulation. And even the prior research, again daing back to the 1990s (it is out of Bruce McEwan's laboratory, a reliable source),found that after 14 days of use, tianeptine alters serotonin transport in the same fashion as yet older antidepressants. More generally, tianeptine’s effects are very much in accord with the current theory of the mechanism of action of other antidepressants, through the induction of neuroresilience in the hippocampus and elsewhere. I reference this evidence in Against Depression, published in 2005; the endnotes provide a short bibliography on the topic.
So (contra Kirsch) it remains easy,in the face of evidence that tianeptine works, to imagine that the benefits of antidepressants are due to their chemical activity. Even the Newsweek piece says that antidepressants succeed in the treatment of severe depression. And while there has always been reason to doubt the "chemical imbalance" theory of depression causation, decades of research ranging across a range of scientific disciplines support the theory that antidepressants operate initially via the drugs' main effects, namely alterning the way the brain handles neurotransmitters. (That's why we have so many structurally diverse "me-too" drugs, ones that all affect serotonin and norepinephrine pathways.) To set aside the testimony of animal model research, brain enzyme resarch, the new work on neurogenesis, and on and on — this stance has the whiff about it of science denial. It is one that a major magazine should have showcased cautiously if at all, and only after having done some serious homework.
As I say, the point about tianeptine is a minor one. It serves only to suggest that before it went to press, the Newsweek essay was not reviewed by anyone familiar with the psychopharmacology literature.
