Are all antidepressants the same?

Historically, the clinician's choice of antidepressant agent has been determined largely by consideration of tolerability, given the perception that the therapeutic efficacy of the various antidepressants was broadly comparable. However, with the advent of the newer, more selective antidepressants, indications of variation in clinical efficacy have begun to emerge. The advent of the selective serotonin reuptake inhibitors has been welcomed by patients, largely owing to their superior tolerability profile compared with older antidepressants. However, severely depressed patients appear to benefit particularly from agents that include a noradrenergic mode of action, such as tricyclic antidepressants and the modern dual-action antidepressants mirtazapine, venlafaxine (at higher doses), and milnacipran. In addition, a noradrenergic component may offer superior efficacy in social functioning. The recent development of a novel, selective norepinephrine reuptake inhibitor (reboxetine) with proven efficacy in a range of depressed patients will permit the investigation of the relevance of the noradrenergic approach. Clinical observations of the effects of the newer, more selective antidepressants are important in our understanding of precise mode of action, variation in efficacy and tolerability, and comparative usefulness in clinical practice.