Mechanism of action of antidepressant medications

The psychopharmacology of depression is a field that has evolved rapidly in just under 5 decades. Early antidepressant medications-tricyclic antidepre ssants (TCAs) and monoamine oxidase inhibitors (MAOIs)-were discovered thro ugh astute clinical observations. These first-generation medications were e ffective because they enhanced serotonergic or noradrenergic mechanisms or both. Unfortunately, the TCAs also blocked histaminic, cholinergic, and alp ha(1)-adrenergic receptor sites, and this action brought about unwanted sid e effects such as weight gain, dry mouth, constipation, drowsiness, and diz ziness. MAOIs can interact with tyramine to cause potentially lethal hypert ension and present potentially dangerous interactions with a number of medi cations and over-the-counter drugs. The newest generation of antidepressant s, including the single-receptor selective serotonin reuptake inhibitors (S SRIs) and multiple-receptor antidepressants venlafaxine, mirtazapine, bupro pion, trazodone, and nefazodone, target one or more specific brain receptor sites without, in most cases, activating unwanted sites such as histamine and acetylcholine. This paper discusses the new antidepressants, particular ly with regard to mechanism of action, and looks at future developments in the treatment of depression.