Noradrenaline (norepinephrine) and depression : role in aetiology and therapeutic implications

In the pharmacological treatment of depression the focus has recently shifted from serotonin (5-hydroxytryptamine; 5-HT) to noradrenaline (norepinephrine), with the advent of new antidepressants such as noradrenaline reuptake inhibitors, noradrenergic and selective serotonergic antidepressants, and serotonin/noradrenaline reuptake inhibitors. It has been suggested that noradrenergic compounds may prove to have beneficial activity in those depressions that are characterised by a 'noradrenergic deficiency syndrome', which is clinically manifested through emotional withdrawal, psychomotor retardation, as well as concentration and memory deficits. The role of noradrenergic mechanisms in the aetiology of depression has been assumed since the catecholamine hypothesis, based on the inhibitory action of tricyclic antidepressants and monoamine oxidase inhibitors on noradrenaline uptake, was formulated. In this article, the aetiological significance of noradrenaline in depression is discussed with regard to the anatomical basis of the noradrenergic system (the locus caeruleus), noradrenaline metabolites, noradrenergic receptors, some aspects of thyroid function and the hypothalamic-pituitary-adrenal axis. The efficacy and tolerability profiles of new antidepressant compounds reboxetine, milnacipran, mirtazapine and venlafaxine are discussed in view of their noradrenergic activity