Do noradrenergic reuptake inhibitors affect serotonergic function in depression?

Abstract

  d-Fenfluramine, a specific 5-HT releasing agent without the catecholamine effects of d,l-fenfluramine, was used as a serotonergic neuroendocrine challenge in subjects with unipolar major depression. Prolactin and cortisol responses to 30 mg d-fenfluramine were measured in patients 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 independent of whether or not patients’ depression responded to treatment. Seven patients were treated with a specific noradrenergic reuptake inhibitor. These patients showed a significant rise in 5-HT-mediated cortisol responses after treatment, independent of whether their depression improved. We conclude that antidepressants which selectively modify noradrenergic function also have effects on 5-HT function as measured by neuroendocrine testing.