Neuroactive steroid concentrations following metyrapone administration in depressed patients and healthy volunteers

Background: There is evidence that treatment with the 11β-hydroxylase inhibitor metyrapone may represent an alternative treatment strategy in major depression. As a consequence of inhibition of cortisol synthesis the overdrive of corticotropin leads to an accumulation of precursor steroids. However, the effects of metyrapone on the concentrations of endogenous neuroactive steroids that modulate ion channels, e.g., the GABAA receptor, have not yet been studied systematically. Methods: Therefore, we quantified the concentrations of an array of neuroactive steroids following administration of 1.5g metyrapone before and after pretreatment with 1 mg dexamethasone in 19 patients suffering from severe depression in comparison to 13 healthy controls by means of a highly sensitive gas chromatography/mass spectrometry analysis. Results: The administration of metyrapone induced a pronouced increase in all neuroactive steroids studied both in patients and controls that was prevented by dexamethasone pretreatment. Conclusions: Thus, the psychotropic properties of endogenous neuroactive steroids may contribute to the antidepressant properties of metyrapone in the treatment of major depression.