Science behind common anti-depressants appears to be backwards, researchers say | Hacker News Reader

Science behind common anti-depressants appears to be backwards, researchers say

sciencedaily.com

32 pointsntakasaki12 comments

The problem is that we've never had an adequate theory of what depression is, and the evidence seems to be that it is far more complex and situational than any one-pill-fixes-all approach could ever attack. The author is correct, but hardly novel or prescient, in noting that there are serious issues with the long-term efficacy of SSRIs and SNRIs (and most other classes of psychoactive drugs). The problems of discontinuation of drug therapy, especially for long-term users, and that the drugs often appear to exacerbate the condition when withdrawn, were noted decades ago.

So, this "study" appears to rehash some old (and valid) critiques of the therapy. All it adds is the interesting hypothesis that depression is "natural" (so is senescence and death) and "beneficial". Which I guess is the novel part.

We may not know what causes depression, but we do know that the constellation of symptoms that we call clinical depression are uniformly unpleasant and all-too-often fatal. So I'm really not convinced that labelling it natural and beneficial absent some pretty strong evidence is all that helpful.

From the sound of it, the important issue in question is depression itself, and not so much the efficacy of SSRIs. If the causes surrounding the physiological roots of depression are unknown or incorrect, no medicinal approach will be able to accurately address the issue, thus always leaving room for the placebo argument.

Not necessarily. We do not need to know the mechanism of an illness to test the efficacy of a treatment. In fact, identifying an efficacious treatment is frequently a key step in developing a model of the underlying illness. There are a number of treatments for depression that have shown promise across multiple studies (and most studies control for placebo effect, and good studies control for active placebo where possible). SSRIs and SNRIs have shown promise for short-term alleviation of symptoms depression, with some serious concerns about long-term use. Cognitive therapy has proven to be quite effective. Some studies of mindfulness (although there are concerns about study quality) indicate great promise there as well.

One thing that is starting to become clear is that effective long-term treatment is likely to require more than one therapy, tailored to the specific situation and needs of the individual patient. Any study, like this one, that implies that depression has a simple mechanism and an obvious cure is about the only one that you can be fairly sure has no validity.

Unfortunately, without access to the full article, I can't say for sure what the authors argue, but another possible explanation for the long delay between treatment onset and the reduction of depression is that SSRIs act as an active placebo.

If so, SSRIs are "active" because they do change something in the brain (unlike a corn starch placebo), but a placebo because the thing changing (serotonin levels) is unrelated to depression. However, since we know something is changing, we believe we'll get better... and thus, we do.

(Think of an active placebo like menthol in dandruff shampoo. Menthol makes the scalp tingle and convinces us it's working, but does nothing for the scalp itself.)

Regardless, there's a lot of gaps and unexplained weirdness in how antidepressants work, so there's still a lot of work to be done.

The active placebo idea strikes me as a plausible one here, and came up in a 2011 article by a former editor of the New England Journal of Medicine which I found pretty thought-provoking:

http://www.nybooks.com/articles/archives/2011/jun/23/epidemi...

Here's what I thought was the key takeaway from the piece:

"Altogether, there were forty-two trials of the six drugs. Most of them were negative. Overall, placebos were 82 percent as effective as the drugs, as measured by the Hamilton Depression Scale (HAM-D), a widely used score of symptoms of depression. The average difference between drug and placebo was only 1.8 points on the HAM-D, a difference that, while statistically significant, was clinically meaningless. The results were much the same for all six drugs: they were all equally unimpressive. Yet because the positive studies were extensively publicized, while the negative ones were hidden, the public and the medical profession came to believe that these drugs were highly effective antidepressants.

Kirsch was also struck by another unexpected finding. In his earlier study and in work by others, he observed that even treatments that were not considered to be antidepressants—such as synthetic thyroid hormone, opiates, sedatives, stimulants, and some herbal remedies—were as effective as antidepressants in alleviating the symptoms of depression. Kirsch writes, “When administered as antidepressants, drugs that increase, decrease or have no effect on serotonin all relieve depression to about the same degree.” What all these “effective” drugs had in common was that they produced side effects, which participating patients had been told they might experience."

Could it also be that a slight adjustment in any area indirectly triggers adjustments in areas that are related to depression? It seems like even a small difference in the balance of all the complicated systems in the brain could potentially have a large effect on overall well-being. Placebo might kick it into the right behavior but the small change might be what allows the placebo to work...? Maybe that's all a placebo is in the first place, I'm not well read on that.

Total speculation, but maybe it works similarly to immune response accelerators like interferon--things that unbalance brain chemistry in general generate a compensating response that sometimes ends up correcting the original problem.

> Could it also be that a slight adjustment in any area indirectly triggers adjustments in areas that are related to depression?

Yes, that's what's happening. Basically any sensory stimulation alleviates depression, including (but not limited to) raising or lowering the levels of pretty much any neurotransmitter.

Given that the monoamine hypothesis was based on fraudulent research to begin with, has been contradicted by pretty much every study since, and has been discredited for years, this result is kind of moot at this point.

You would hope so, but unfortunately SSRIs are still big sellers for pharmaceutical companies.

Is there a breakdown in that regard in relation to http://www.selegiline.com/ ?

>The best available evidence appears to show that there is more serotonin being released and used during depressive episodes, not less, the authors say.

During my brief stint on an SSRI I felt as numb as I ever had in the depths of depression, maybe even moreso - enough that I wasn't worried about how numb I was. I stopped taking them because of that, it felt backwards to me as well.

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