I've not had time to thoroughly read this yet. But on the heels of another study published a few weeks ago (I blogged on it here) showing that SSRIs have little therapeutic effect if you include the (unflattering) clinical trials the industry had previously hidden, PLOS Medicine now publishes a larger study -- a meta-analysis of all available data on clinical trials of SSRIs -- that shows that "compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression" -- and that (as the editors write) "the researchers conclude that there is little reason to prescribe new-generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective."
If this holds up, this is a huge development indeed. Many people who take SSRIs say they help them, and they know they have a physiological effect because of subtle or more blatant side-effects -- everything from itching, dry mouth, and sexual problems to slight tingling or numbing of the lips or a sort of spacey feel. Those things often kick in within a few days. Then, for those who do feel better, the improvement follows 3 to 6 weeks later. But is the improvement a placebo effect and/or the result of attentive treatment via psychotherapy? The association of the felt physiological changes with improvement makes it seem clear the drug helps. This study appears to argue -- adamantly -- otherwise -- or, at best, that SSRIs work because the drug's felt physiological side-effects strengthen the placebo effect.
It'll be interesting to see how this plays out.
Some of the editors' summary is below. The paper itself is here, and free.
These findings suggest that, compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression, but show significant effects only in the most severely depressed patients. The findings also show that the effect for these patients seems to be due to decreased responsiveness to placebo, rather than increased responsiveness to medication. Given these results, the researchers conclude that there is little reason to prescribe new-generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective. In addition, the finding that extremely depressed patients are less responsive to placebo than less severely depressed patients but have similar responses to antidepressants is a potentially important insight into how patients with depression respond to antidepressants and placebos that should be investigated further.