Agents that inhibit selectively the neuronal reuptake of serotonin but not catecholamines, and that do not interact directly with neurotransmitter receptors, can have antidepressant activity clinically. Their antidepressant action presumably is initiated by enhanced serotonergic input to other neuronal systems in brain, which leads to primary and secondary (adaptive) changes in neurotransmission and results in remission of depressive symptoms.