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

There is evidence for a differential alteration in the concentrations of 3α-reduced neuroactive steroids in major depression. Because it has been suggested that fluoxetine may shift the activity of the 3α-hydroxysteroid oxidoreductase towards the reductive direction, treatment of major depression may be accompanied by a further increase in plasma 3α,5α-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 3α,5α-tetrahydroprogesterone, 3α,5β-tetrahydroprogesterone (THP) and THDOC by means of a highly sensitive combined gas chromatography/mass spectrometry analysis. Compared to control subjects, concentrations of THDOC were higher in depressed patients and decreased after fluoxetine treatment. In contrast, THP concentrations were lower in depressed patients and increased after fluoxetine treatment. Our results give further evidence for a disequilibrium of 3α-reduced neuroactive steroids in major depression, which is normalized by treatment with fluoxetine.