Triple reuptake inhibitors: the next generation of antidepressants

Depression has been associated with impaired neurotransmission of serotonergic, norepinephrinergic, and dopaminergic pathways, although most pharmacologic treatment strategies for depression enhance only serotonin and norepinephrine neurotransmission. Current drug development efforts are aimed at a new class of antidepressants which inhibit the reuptake of all three neurotransmitters in the hope of creating medications with broader efficacy and/or quicker onset of action. The current review explores limitations of presently available antidepressants and the history and premise behind the movement to devise triple reuptake inhibitors. The evidence for and against the claim that broader spectrum agents are more efficacious is discussed. Examples of triple reuptake inhibitors in development are compared, and preclinical and clinical research with these agents to date is described.