Are All Antidepressants the Same?

Historically, the clinician’s choice of antidepressant agent has been determined largely by considerationof tolerability, given the perception that the therapeutic efficacy of the various antidepressantswas broadly comparable. However, with the advent of the newer, more selective antidepressants, indicationsof variation in clinical efficacy have begun to emerge. The advent of the selective serotoninreuptake inhibitors has been welcomed by patients, largely owing to their superior tolerability profilecompared with older antidepressants. However, severely depressed patients appear to benefit particularlyfrom agents that include a noradrenergic mode of action, such as tricyclic antidepressants and themodern dual-action antidepressants mirtazapine, venlafaxine (at higher doses), and milnacipran. Inaddition, a noradrenergic component may offer superior efficacy in social functioning. The recent developmentof a novel, selective norepinephrine reuptake inhibitor (reboxetine) with proven efficacy ina 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 importantin our understanding of precise mode of action, variation in efficacy and tolerability, and comparativeusefulness in clinical practice.