History time. Antidepressant pharmacotherapy was actually discovered in the 1950s when reserpine, then used as an antihypertensive, was noted to cause depressio

History time. Antidepressant pharmacotherapy was actually discovered in the 1950s when reserpine, then used as an antihypertensive, was noted to cause depression. Reserpine acts by blocking the transmission of neurotransmitters 5HT, NE, and DA. Given that over twenty drugs, all with different actions on different neurotransmitters, have shown efficacy in depressed patients over the last 60 years, I think it would be rather shortsighted to dismiss the significant body of literature dedicated to the role of neurotransmitters in depression. There are certainly many theories, and depression is a complicated disease. It is primarily modified by neurotransmitters, however. That much should be clear. Beta adrenergic receptor sensitivity and downregulation are also involved - but to what extent? Hypersecretion of cortisol (or lack of cortisol suppression) is also a factor - but to what extent? Even thyroid hormones are implicated. Like I said, I'm not saying there is no inflammatory problem in depression - I said that we have no antidepressants based on this idea (and as far as I know, there are none in the pipeline in at least Phase II trials). Do I think inflammation is involved? Yes, I do. Do I think it's directly going to lead to more treatments for depression? No, I don't.