SSRIs Versus SNRIs: Mechanisms of action

Selective noradrenergic and serotonergic antidepressants are becoming widely used in the treatment of depression. Although it is clear that depression is not caused by simple deficit or excess of serotonin (5-HT) or norepinephrine (NE), and the specific impairment that underlies depression continues to be unclear, it is likely that in some more vulnerable individuals, abnormalities in monoamine function may contribute to the development of depressive episodes. It has been hypothesized that drugs that selectively inhibit 5-HT andNE reuptake enhance neurotransmission in normal noradrenergic or serotonergic neurons, and through a time-dependent process restore function to brain areas that are modulated by NE and 5-HT. It appears that immediate effects of these drugs on monoamine function are necessary for their therapeutic action. While both NE and 5-HT systems seem to be involved in the antidepressant action, and interactions between the two systems are numerous, neither of the two systems appears to be the single final common pathway for the antidepressant response. Noradrenergic selective drugs appear to be primarily dependent on the availability ofNEfor their effects, and serotonergic selective drugs need available 5-HT for their effects. Since an enhancement ofNE and 5-HT transmission can lead to therapeutic effects, drugs that act on both neurotransmitter systems may have a therapeutic advantage and be effective in a broader range of patients with depression.