I’m continuing my review of the literature on antidepressants. Today we cover a systematic review in PLoS Medicine, which is one of the new open access journals that anyone can access. It’s been amazing to watch these open-source journals revolutionize access to the literature for people like me who don’t have university access.
Here’s the link to the full text article.
The authors are diverse and from different countries, and they’re only considering FDA submitted data. I’ll let them summarize their findings:
“Using complete datasets (including unpublished data) and a substantially larger dataset of this type than has been previously reported, we find that the overall effect of new-generation antidepressant medications is below recommended criteria for clinical significance. We also find that efficacy reaches clinical significance only in trials involving the most extremely depressed patients, and that this pattern is due to a decrease in the response to placebo rather than an increase in the response to medication.”
Let me give my own translation: Unless someone is VERY, VERY depressed, it was hard to justify using these new antidepressants, and then only because there are no non-pharmacological solutions that seem to work anymore. In other words, it’s not that the drugs worked particularly well in any case, but the placebo effect was no longer of any benefit. There’s a figure that illustrates this pretty well:
As you start at the left with the people who started out less severely depressed, placebo outperforms the new drugs by a small amount. Then, as the benefit of placebo decreases, the difference between the two increases. It’s not that the drugs get that much more effective in people with stronger symptoms, but the difference increases until finally we enter the “green zone”, the area where the drug outperforms the placebo enough to be clinically relevant. By that point the drug is still not showing much improvement.
I personally found that pretty surprising, given that the data they are mining for the review was in the FDA’s hands. I went into this evaluation with a general impression that SSRIs and the like work only in cases where there’s an underlying serotonin problem (brain chemistry issues), but now I see that this isn’t going to be that straightforward.
My one concern is that in grouping all these studies together, there seems to be a lot of diversity in the kind of results produced. I wonder what caused those outlier triangles with high improvement (high on the Y axis).
The investigation continues!