Assessment of serotonergic function in major depression using d-fenfluramine: relation to clinical variables and antidepressant response

d-Fenfluramine, a specific serotonin (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.

Patients were given 30 mg of d-fenfluramine orally, and prolactin and cortisol responses were measured over the following 5 hours. Endocrine responses were examined in relation to clinical variables and subsequent response to antidepressant treatment.

5-HT-mediated cortisol responses at baseline were inversely correlated with depression severity on the Montgomery Asberg Depression Rating Scale, Bech Melancholia Scale, and Clinical Global Impression scale. Prolactin responses were inversely correlated with anxiety on the Brief Symptom Inventory. A higher initial cortisol response to d-fenfluramine predicted a subsequent good antidepressant response.

We conclude that: a) the severity and symptom profile in major depression may be closely related to 5-HT dysfunction; and b) higher cortisol responses to d-fenfluramine predict a preferential response to treatment.