THE RELATIONSHIP BETWEEN THE EFFECTS OF METYRAPONE TREATMENT ON DEPRESSED MOOD AND URINARY STEROID PROFILES

In order to investigate mechanisms by which the adrenal 11 beta-hydrox ylase inhibitor metyrapone might exert its antidepressant effect, we u sed gas chromatography to analyse the 24 h urinary steroid profiles fr om six females with major depression taking part in a trial of metyrap one (2-4 g/day) as an antidepressant. Due to concurrent administration of hydrocortisone (30 mg/day), plasma cortisol levels were not signif icantly reduced. Treatment with metyrapone resulted in greatly increas ed urinary excretion of Il-deoxy corticosteroids, including the GABA-m odulatory steroid tetrahydro-11-deoxycorticosterone (from 68+/-34 to 2 19+/-75 mu g/24 h, p <.05). Metyrapone also had multiple extra-adrenal effects on corticosteroid metabolism, including inhibition of the per ipheral conversion of cortisone to cortisol as demonstrated by a signi ficant decrease in the ratio of 11 beta-hydroxy/11-oxo metabolites of cortisol (from 0.81 +/- 0.08 to 0.46 +/- 0.04, p <.01). The decreased Montgomery-Asberg Depression Rating Scale scores seen during treatment with metyrapone did not correlate with changes in plasma cortisol, bu t did correlate significantly with total 11-deoxycortisol metabolites (r =0.778, n =12, p <.01). We conclude that, in addition to decreased cortisol synthesis, increased secretion of cortisol precursors and red uced local bioavailability of cortisol may play a role in the antidepr essant effect of metyrapone. Copyright (C) 1996 Elsevier Science Ltd.