The claim that “SSRIs don’t work” or “SSRIs are mostly just placebo” is most commonly associated with Irving Kirsch, a man with the awesome job title of “Associate Director Of The Program For Placebo Studies at Harvard”.(fun fact: there’s actually no such thing as “Placebo Studies”, but Professor Kirsch’s belief that he directs a Harvard department inspires him to create much higher-quality research.) In 1998, he published a meta-analysis of 19 placebo-controlled drug trials that suggested that almost all of the benefits of antidepressants were due to the placebo effect.There was never much more evidence for the serotonin hypothesis than that chemicals that increased serotonin tended to treat depression – making the argument that “antidepressants are biochemically justified because they treat the low serotonin that is causing your depression” kind of circular.Saying “Serotonin treats depression, therefore depression is, at root, a serotonin deficiency” is about as scientifically grounded as saying “Playing with puppies makes depressed people feel better, therefore depression is, at root, a puppy deficiency”.Psychiatrists denounced him, saying that you can choose pretty much whatever studies you want for a meta-analysis.After biding his time for a decade, in 2008 he struck back with another meta-analysis, this being one of the first papers in all of medical science to take the audacious step of demanding all the FDA’s data through the Freedom of Information Act.There is large publication bias in the antidepressant literature 4.The effect size of antidepressants is clinically insignificant 5.
While it is an exaggeration to say they have no side effects (see above) they are an obvious improvement over older classes of medication in this regard.For patients with very severe depression, the benefit of medications over placebo is substantial.Of course, a very large number of antidepressants are given to people with mild or moderate depression. Let me sort the debate about antidepressants into a series of complaints: 1.The whole thing became less tenable with the discovery that several chemicals that didn’t increase serotonin were also effective antidepressants – not to mention one chemical, tianeptine, that decreases serotonin.