Venlafaxine: A novel antidepressant that has a dual mechanism of action

Major depressive disorder (MDD) is a common affective disorder that is associated with a range of psychiatric disturbances. The pathophysiology of MDD is commonly believed to involve the reduced availability of the monoamines, serotonin (5-HT) and norepinephrine (NE), the enhancement of which is also believed to mediate, at least in part, the therapeutic effects of antidepressants. The first-generation antidepressants, the tricyclic antidepressants (TCAs), provide considerable efficacy but have several limitations, including (1) delayed onset of action, (2) intolerable or distressing side effects, (3) low therapeutic index, and (4) a significant proportion of nonresponders. The second-generation antidepressants, the selective-serotonin-reuptake inhibitors (SSRIs), mitigate some of the side effects associated with the TCAs by selectively inhibiting the reuptake of 5-HT. Venlafaxine is a new antidepressant that blocks reuptake of both 5-HT and NE. It, like the SSRIs, has a relatively benign side-effect profile. In addition, it may exert a rapid onset of action, and it appears to be particularly effective in moderate-to-severe depression and in patients who have treatment-refractory depression. Depression 4:48–56 (1996). © 1997 Wiley-Liss, Inc.