Okay, I'll bite: > Here's what the science says: "... antidepressant medications have reported only modest benefits over placebo treatment, and when unpublishe

Okay, I'll bite: > Here's what the science says: "... antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance." With all due respect, read the paper you linked to! Here's what it says in the places you didn't quote: "Meta-analyses of antidepressant efficacy based on data from published trials reveal benefits that are statistically significant, but of marginal clinical significance [1]." "Although the difference between these means easily attained statistical significance (Table 2, Model 3a), it does not meet the three-point drug–placebo criterion for clinical significance used by NICE." "Although drug type and duration of treatment were unrelated to improvement, the drug versus placebo difference remained significant, and amount of improvement was a function of baseline severity (Table 2, Model 1a)." "The difference between drug and placebo exceeded NICE's 0.50 standardized mean difference criterion at comparisons exceeding 28 in baseline severity." > First, you're overlooking the fact that the studies that got SSRIs approved in the first place relied on animal studies using the same animals. SSRIs were approved several decades ago, but studies in the last decade still show the same effects, e.g. the study I linked to above, which was conducted in 2009 using fluoxetine, which was approved in 1987. The lifespan of a mouse is around a year, so there is zero chance that any of the animals are the same. In Figure 1, it reproduces the result that antidepressants reduce depressive behaviors in mouse models on a variety of tests. This is not an isolated result; basically all of the rodent studies show similar findings. > Second, imagine a scientist saying "... just because mice genetically depleted of serotonin do not show depression-like symptoms does not mean that toying with serotonin levels in a normal brain cannot alleviate depression." Surely you see the logical error you're making here -- the argument essentially says, "if it hasn't been disproven, then it might be true." It equates an absence of evidence, with evidence. This is in response to your claim that "the drugs could not possibly work." The drugs can work even if serotonin-depleted animals are not depressed. And as I've stated, there is an abundance of evidence that the drugs do work in mice, even though serotonin-depleted mice are not depressed. > > In fact, antidepressant treatment does alleviate depression in mice ... > Not according to the FDA's meta-analysis quoted above. That meta-analysis is in humans. Mice are not humans! That is a big reason why it's so hard to develop good antidepressants in the first place. > Apart from a well-documented Placebo effect, which therapeutic action are you alluding to? The therapeutic action in mice, which is replicated in the study I linked to and many others. As far as DBS goes, one of the problems with determining if DBS actually works for depression is that most studies have not been placebo controlled. Also, the largest study that I'm aware of was recently shut down by the FDA for lack of efficacy: http://neurocritic.blogspot.com/2014/01/broaden-trial-of-dbs-for-treatment.html http://neurocritic.blogspot.com/2014/01/broaden-trial-of-dbs...