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Four years ago I\xa0examined the claim\xa0that SSRIs are little better than placebo. Since then, some of my thinking on this question has changed.

First, we got\xa0Cipriani et al\u2019s meta-analysis\xa0of anti-depressants. It avoids some of the pitfalls of Kirsch and comes to about the same conclusion. This knocks down a few of the lines of argument in my part 4 about how the effect size might look more like 0.5 than 0.3. The effect size is probably about 0.3.

Second, I\u2019ve seen enough to realize that the anomalously low effect size of SSRIs in studies should be viewed not as an SSRI-specific phenomenon, but as part of a general trend towards much lower-than-expected effect sizes for every psychiatric medication (every medication full stop?). I wrote about this in my\xa0post on melatonin:

The consensus stresses that melatonin is a very weak hypnotic. The Buscemi meta-analysis cites this as their reason for declaring negative results despite a statistically significant effect \u2013 the supplement only made people get to sleep about ten minutes faster. \u201cTen minutes\u201d sounds pretty pathetic, but we need to think of this in context. Even the strongest sleep medications, like Ambien, only show up in studies as getting you to sleep ten or twenty minutes faster;\xa0this NYT article\xa0says that \u201cviewed as a group, [newer sleeping pills like Ambien, Lunesta, and Sonata] reduced the average time to go to sleep 12.8 minutes compared with fake pills, and increased total sleep time 11.4 minutes.\u201d I don\u2019t know of any statistically-principled comparison between melatonin and Ambien, but the difference is hardly (pun not intended) day and night. Rather than say \u201cmelatonin is crap\u201d, I would argue that all sleeping pills have measurable effects that vastly underperform their subjective effects.

Or take benzodiazepines, a class of anxiety drugs including things like Xanax, Ativan, and Klonopin. Everyone knows these are effective (at least at first, before patients develop tolerance or become addicted). The studies find them to have\xa0about equal efficacy as SSRIs. You could\xa0almost\xa0convince me that SSRIs don\u2019t have a detectable effect in the real world; you will never convince me that benzos don\u2019t. Even\xa0morphine for pain\xa0gets an effect size of 0.4, little better than SSRI\u2019s 0.3 and not enough to meet anyone\u2019s criteria for \u201cclinically significant\u201d.\xa0Leucht 2012provides similarly grim statistics for everything else.

I don\u2019t know whether this means that we should conclude \u201cnothing works\u201d or \u201cwe need to reconsider how we think about effect sizes\u201d.