Effects of Antidepressant Treatment on Neuroactive Steroids in Major Depression

OBJECTIVE: There is evidence from animal studies that fluoxetine may enhance the concentrations of neuroactive steroids. Therefore, the authors investigated whether clinically effective treatment with antidepressants may alter the concentrations of neuroactive steroids in patients suffering from a major depressive episode. METHOD: In the first study, eight drug-naive outpatients with major depression were studied during treatment with fluoxetine. In a complementary study, 11 inpatients with major depression were studied during a severe depressive episode and after recovery following treatment with different antidepressants. Plasma samples were quantified for neuroactive steroids by means of a highly sensitive and specific combined gas chromatography/mass spectrometry analysis. RESULTS: During depression, there was a significant decrease in 3α, 5α-tetrahydroprogesterone (3α, 5α-THP) and 3α, 5β-THP concentrations, both of which are positive modulators of the γ-aminobutyric acid_A receptor, and a concomitant increase in 3β, 5α-THP levels. This dysequilibrium of neuroactive steroids could be corrected by treatment with different antidepressants. CONCLUSIONS: These results provide the first clinical evidence of a possible role of neuroactive steroids in successful antidepressant therapy. (Am J Psychiatry 1998; 155:910–913)