DO NORADRENERGIC REUPTAKE INHIBITORS AFFECT SEROTONERGIC FUNCTION IN DEPRESSION

d-Fenfluramine, a specific 5-HT releasing agent without the catecholam ine effects of d,l-fenfluramine, was used as a serotonergic, neuroendo crine challenge in subjects with unipolar major depression. Prolactin and cortisol responses to 30 mg d-fenfluramine were measured in patien ts at baseline. Patients were then randomly assigned to treatment for 6 weeks with a specific noradrenergic, reuptake inhibitor, a tricyclic antidepressant, or placebo. Response to antidepressant treatment was assessed, and patients underwent further testing with d-fenfluramine. Prolactin responses were increased by treatment, but this was independ ent of whether or not patients' depression responded to treatment. Sev en patients were treated with a specific noradrenergic reuptake inhibi tor. These patients showed a significant rise in 5-HT-mediated cortiso l responses after treatment, independent of-whether their depression i mproved. We conclude that antidepressants which selectively modify nor adrenergic function also have effects on 5-HT function as measured by neuroendocrine testing.