A review of the efficacy of serotonergic and noradrenergic reuptake inhibitors for treatment of major depression

Both norepinephrine and serotonin mediate the effects of antidepressant drugs and a reasonable question is whether the efficacy of these two mechanisms of action is similar. Previous reviews comparing selective serotonergic drugs with tricyclic antidepressants found no differences, but the tricyclic drugs are heterogeneous with respect to mechanism of action. The current review focuses on studies comparing serotonergic agents with antidepressants that act primarily on norepinephrine. The literature was reviewed to identify double-blind, random assignment studies comparing SSRIs and NRIs, with adequate description of methods and outcome. Fifteen studies were identified, which had enrolled a total of over 1500 patients. The rates of response with SSRIs and NRIs, 61.4% and 59.5%, were neither meaningfully nor significantly different. Few predictors of response were identified in these studies. Noradrenergic and serotonergic antidepressants appear to be equally effective. It remains to be determined if they treat the same or different patients.