CORTISOL SYNTHESIS INHIBITION - A NEW TREATMENT STRATEGY FOR THE CLINICAL AND ENDOCRINE MANIFESTATIONS OF DEPRESSION

Evidence exists that oversecretion of cortisol may be responsible for the clinical manifestations and serotonergic abnormality in depressive illness. Using the cortisol synthesis inhibitor ketoconazole, we inve stigated the effects of directly lowering cortisol on the symptoms and the response of prolactin (PRL) to d-fenfluramine in eight patients s uffering from major depression. Prolactin responses to d-fenfluramine were measured, and patients were treated with 400-600 mg of ketoconazo le for 4 weeks, after which they were retested. Five patients treated with ketoconazole recovered from their depression, while the other thr ee had decreases in their Hamilton Depression Rating Scale (HAMD) scor es of less than or equal to 50% and were deemed partial responders, Po sttreatment prolactin responses to d-fenfluramine were higher than pre treatment values, Ketoconazole normalizes the blunted prolactin respon ses to d-fenfluramine and may be an effective method by which to treat depression. This implies that hypercortisolemia may responsible for t he clinical features and serotonergic subsensitive observed in depress ion.