Fluoxetine decreases concentrations of 3 alpha,5 alpha-tetrahydrodeoxycorticosterone (THDOC) in major depression

There is evidence for a differential alteration in the concentrations of 3 alpha-reduced neuroactive steroids in major depression. Because it has been suggested that fluoxetine map shift the activity of the 3 alpha-hydroxyste roid oxidoreductase towards the reductive direction, treatment of major dep ression may be accompanied by a further increase in plasma 3 alpha,5 alpha- tetrahydrodeoxycorticosterone (THDOC) concentration. We studied eight male depressed patients before and after treatment with fluoxetine and compared them to healthy age-matched control subjects. Blood samples were quantified for 3 alpha,5 alpha-tetrahydroprogesterone, 3 alpha,5 beta-tetrahydroproge sterone (THP) and THDOC by means of a highly sensitive combined gas chromat ography/mass spectrometry analysis. Compared to control subjects, concentra tions of THDOC were higher in depressed patients and decreased after fluoxe tine treatment. Tn contrast, THP concentrations were lower in depressed pat ients and increased after fluoxetine treatment. Out results give further ev idence for a disequilibrium of 3 alpha-reduced neuroactive steroids in majo r depression, which is normalized by treatment with fluoxetine. (C) 2000 El sevier science Ltd. All rights reserved.