Im always concerned about any of those types of serotonin receptor agonists because when i take meds that mildly activate any of the serotonin receptors I feel TEN times worse - wired and jittery. I was reading an interesting article about how elecated cytokines like good old TNF alpha again are often found to be elecvated in depression. They think that the sickness type symptoms of depression might actually be coming from that and are now suggesting a course of antidepressant and cox inhibitors in some depressed patients. They found that chronic activation of TNF alpha leads to an actual decrease in serotonin generation - not a problem with reuptake or how long it is active, but just an actual loss of it from the start. When my Ank Spond plays up I always feel kinda washed out and mildly depressed (not so much sad, but just cant be bothered feeling). My Rheumy said that all of his AS and Fibro patients are the same. But it got me wondering - perhaps the serotonic pathways are part of the problem for me atleast if I feel that way when TNF alpha is high and when my serotonic receptors are highly sensitive suggesting upregulation. Sorry way off topic!