Noradrenergic Approaches to Antidepressant Therapy

A decade of remarkable research in neuroscience has given us a much more complete picture of how thecentral nervous system works and, in some instances, how the brain does not work when patients developdepression. Preclinical and clinical studies have shown that stimulation of the serotonergic system leads tonoradrenergic effects and vice versa, confirming that the serotonin and norepinephrine systems are intimatelyconnected in the central nervous system. Although medications that target the serotonergic neurotransmittersystem have recently dominated antidepressant therapy, atypical antidepressants—with eithermixed serotonergic and noradrenergic effects or exclusively noradrenergic effects—have been shown to beclinically efficacious medications. This increased understanding of the interrelationship between neurotransmittersystems has renewed interest in the role of neurotransmitters other than serotonin in the treatment ofdepression. With the introduction of reboxetine, a very selective norepinephrine reuptake inhibitor, researchershave had an opportunity to study the unique effects of norepinephrine in the etiology and treatment ofdepression. Ultimately, differences in neurotransmitter profiles may influence therapeutic potentials of antidepressants.For example, influencing norepinephrine may affect the expression of energy and interest,while influencing serotonin may affect impulse control and influencing dopamine may affect drive. Cliniciansnow have a range of antidepressants with variable neurotransmitter effects, different side effect profiles,and some interesting differences in functional utility in their armamentarium for treating depression.