SSRIs, dopamine and depression

[hypnagogue]

There is actually substantial critique against the simple "chemical hypothesis" that depression is caused by low levels of serotonin. See for instance:

http://www.mindhacks.com/blog/2005/05/is_depression_a_brai.html
http://www.mindhacks.com/blog/2005/11/depression_and_the_l.html
http://www.nature.com/cgi-taf/DynaPage.taf?file=/nrn/journal/v6/n3/full/nrn1629_fs.html

Coincidentally, depression is essentially defined as a condition of lowered interest and pleasure. If you are depressed then you lose interest in things that used to interest you and you have a difficult time deriving pleasure from formerly pleasing activities. Therefore it's no surprise if there is some anecdotal evidence that drugs targetting the dopamine system can help alleviate some symptoms of depression. After all, the hallmarks of the excited dopamine system are heightened feelings of interest and pleasure.

So why is it that antidepressant drugs target the dopamine system? I'm not sure, but it may be because the dopamine system isn't a good thing to mess with. Another hallmark of exciting the dopamine system is that it induces strong feelings of wanting, craving-- so any drug that excites it is likely to be highly addictive. You can get rats to compulsively drink a bitter salt solution that they otherwise hate if you stimulate their dopamine system, even while they exhibit behaviors normally indicative of displeasure. And of course in the human case, there are any number of drugs that affect the dopamine system that are notoriously addictive and thus damaging in the long run. So it's strong stuff.

Of course, that's not all. Excessive levels of dopamine can lead to paranoid, delusional, and otherwise warped thinking-- see schizophrenia for an extreme case. Another potential danger is that regular use of a dopamine agonist could possibly lead to lowered biological production of dopamine in the brain. Cessation of the drug, combined with lowered levels of internally produced dopamine, could then cause a sharp drop in dopamine levels. But dopamine levels that are too low are also bad. For extreme examples of what can go wrong with levels of dopamine that are too low, see Huntington's Disease and Parkinson's Disease. (Again, not coincidentally, Huntington's and Parkinson's are both often associated with depression.)

 

[Danger]

I don't actually have time to read your whole post right now, but my understanding of the term 'depression' refers to depressed activity of the neurological functions rather than 'sadness' or 'lethargy' or whatever. That's caused by decreased levels of neurotransmitters.
I refer to my Wellbutrin and Cilaxis as my "I don't want to kill anybody today" pills. There's a very solid reason for that.

 

[hypnagogue]

The clinical notion of depression is primarily about one's thoughts, feelings, and behaviors. It's to do with one's subjective well-being and functioning in the world. See e.g. here. There are various hypotheses about the neural basis of depression (and it should not go unsaid that some parties have a vested financial interest in advertising some of those hypotheses), but these are all secondary to the primary phenomena. If you have the thoughts, feelings, and behaviors typical of depression, then you are clinically diagnosed as depressed, regardless of what the causes may be.

This isn't to say that SSRIs are ineffectual. For some people they seem to be effective for alleviating depression. But it's still an open question as to what the causal mechanisms are that underlie the helpfulness of taking SSRIs when they do happen to be helpful.

 

[Danger]

Hmm... I'll take your word for it regarding the definition.
In my case, though, seratonin is almost certainly the main culprit. Wellbutrin is a carpet-bomber that targets glutamin, seratonin and dopamine. Taking 2 of them a day was helpful, but not terribly effective. When I swapped 1 of them out for the Cilaxis, which is an SSRI, things improved drastically.