
Science behind common anti-depressants appears to be backwards, researchers say - ntakasaki
http://www.sciencedaily.com/releases/2015/02/150217114119.htm
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ajarmst
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withdrawn, were noted decades ago.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.

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geoffsanders
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.

~~~
ajarmst
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.

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KingMob
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.

~~~
benbreen
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...](http://www.nybooks.com/articles/archives/2011/jun/23/epidemic-
mental-illness-why/)

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."

~~~
heurist
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.

~~~
Alex3917
> 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.

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Alex3917
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.

~~~
superobserver
Is there a breakdown in that regard in relation to
[http://www.selegiline.com/](http://www.selegiline.com/) ?

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heurist
>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.

