NEUROACTIVE STEROID CONCENTRATIONS FOLLOWING METYRAPONE ADMINISTRATION IN DEPRESSED-PATIENTS AND HEALTHY-VOLUNTEERS

Background: There is evidence that treatment with the 11 beta-hydroxyl ase inhibitor metyrapone may represent an alternative treatment strate gy in major depression, As a consequence of inhibition of cortisol syn thesis the overdrive of corticotropin leads to an accumulation of prec ursor steroids. However, the effects of metyrapone on the concentratio ns of endogenous neuroactive steroids that modulate ion channels, e.g. , the GABA(A) receptor, have not vet been studied systematically. Meth ods: Therefore, we quantified the concentrations of an array of neuroa ctive steroids following administration of 1.5g metyrapone before and after pretreatment with I mg dexamethasone in 19 patients suffering fr om severe depression in comparison to 13 healthy controls by means of a highly sensitive gas chromatography/mass spectrometry analysis. Resu lts: The administration of metyrapone induced a pronouced increase in all neuroactive steroids studied both in patients and controls that wa s prevented by dexamethasone pretreatment. Conclusions: Thus, the psyc hotropic properties of endogenous neuroactive steroids may contribute to the antidepressant propel-ties of metyrapone in the treatment of ma jor depression, (C) 1998 Society of Biological Psychiatry.