Serenity - OMG, I just spent an hour and a half replying to you for a third time. I don't know what I did the first time, my reply didn't post and I didn't realize it; the second: I stopped to have supper (it was the third time my wife had called - but I didn't hear the first two - and the cat figured out how to work the switch on the powerbar - she just had to protect us from that faint red glow!). Now, my browser quits! DOH!! That is truly heartbreaking, as well as a pain where I wouldn't put a window.

I just came off an 8 day in a row stretch at work (another story) and they haven't returned my internet computer (still another story), so I have not had access to the site. Plus, recently I haven't had the energy to think at all (haven't been this low in awhile). This may be coming too late but here goes (I've pretty much got this organized in my head by now ).

serotonin in the brain. Serotonin is one of hundreds of <A target="_blank" HREF=http://129.195.254.70/cgi-bin/HONselect?browse+D14.600#MeSH> neurotransmitters</A> (neuromodulators, etc.) that carry electrical signals (information entering and leaving the brain) from one nerve cell to another. A lack of serotonin ultimately results in the cluster of symptoms that we call depression. Serotonin is not the "cause" of depression, but we can often relieve depressive symptoms by increasing levels of this substance in the brain using serotonergic antidepressants.

As soon as you start taking a serotonergic antidepressant the levels of serotonin in the brain are increased. This is a shock to the brain; it has been running on low serotonin for some time. All neurotransmitters are linked to each other in very intricate ways; if you change the concentration of one neurotransmitter, you change the concentration and activity of them all. A brain that is functioning with low levels of serotonin is still functioning, albeit below its potential. In order to compensate for the lack of serotonin, other neurotransmitters modify (lessen) their effects on serotonergic neurons (nerve cells) and the number of receptors for serotonin increase in number.

Adding serotonin to this mix upsets this statis quo. Now the serotonin receptors begin to fire excessively due to the increased number (and possibly sensitivity) of the brain's widespread serotonin receptors, as well as the decreased regulation of serotonin by other neurotransmitters. The body now has to downregulate (decrease) the number (and perhaps sensitivity) of it's receptors, as well as adjust the concentrations of the other neurotransmitters, in order to "normalize" the flow of electrical signals through, and between, serotonergic neurons (serotontin-containing nerve cells). This takes time; the time it takes for neurons differs in different people, but usually takes between 2 and 16 weeks, (unsurprisingly) the same duration of time it usually takes an antidepressant to begin working. That excess of serotonin at the beginning of therapy results in the symptoms that I call the "start-up" side effects (eg. increased anxiety, pressure in the head, nausea, etc.).

The normalizing of the brain concentration and activity of serotonergic neurons (often) results in a resolution of depressive symptoms. Antidepressants do not "cure" depression; the original psychological problem(s) that "caused" the depression in the first place must be resolved for that to happen. Ordinarily I would make a disclaimer regarding major depressions resulting from a genetic predisposition are incurable and one must stay on antidepressant (antianxiety) medication for life. Recently I have begun to think that if researchers are able to come up with a way to decrease the brain's sensitivity to stressors that result in major depression (ie. "raise the bar" so that increased stress is needed to initiate depression - or, for those keeping score, make it harder to uncouple the HPA axis).

As for the use of Xanaxª (alprazolam) to deal with the start-up side effects of serotonergic antidepressants (like doxepin), I do recommend it in most anxiety-type disorders (panic disorder, GAD, etc.). There is no harm in using a benzodiazepine for the short term, at least until the anxiolytic activity of the doxepin kicks in.

Sorry again for the delay. - Cam

To fully understand a concept is to be unable to convey it's intricacies verbally; only when one can sense it emotionally, does one understand.