One theory about antidepressants is that they relieve depression by encouraging neurogenesis — the creation of new neurons. Neuroskeptic reviews a study that argues against this idea.
the neurogenesis hypothesis has problems of its own. A new paper claims to add to what seems like a growing list of counter-examples: Ageing abolishes the effects of fluoxetine on neurogenesis.
The researchers, Couillard-Despres et. al. from the University of Regensburg in Germany, found that fluoxetine (Prozac) enhances hippocampal neurogenesis in mice – as expected – but found in addition that this only holds true in young mice. In middle-aged and older mice, there was no such effect. That’s a new finding, and a very important one.
I’ve seen SSRIs work on enough people to believe they DO work. But as the various proposed mechanisms are cast increasingly into doubt, and sober evaluations of their efficacy increasingly show them barely besting placebo, it’s reasonable to wonder how much of their effect is placebo. Update Jan 21 2009: This post from Bad Science does exactly such wondering. Among other things it cites a 2002 JAMA study that showed that the placebo effect had grown significantly in antidepressant clinical trials — suggesting it had perhaps risen along with public confidence in SSRIs. So will it drop if and as public confidence in SSRI efficacy falls? Many, many interesting questions here…
Update: As Neuroskeptic points out in the comments, this study of older mice is only a first study of its kind, and only a small one, and with its own quirks; as with any single study, one can’t consider it definitive. Yet it points out some possible limitations of the database underlying the neurogenesis theory, for if SSRIs work by encouraging neurogenesis but don’t do so in older patients, why do SSRIs relieve depression (to the extent they do) in older patients as well as young? With luck we’ll see more work on this.