EFFECTS OF ANTIDEPRESSANT TREATMENT ON NEUROACTIVE STEROIDS IN MAJOR DEPRESSION

Objective: There is evidence from animal studies that fluoxetine may e nhance the concentrations of neuroactive steroids. Therefore, the auth ors investigated whether clinically effective treatment with antidepre ssants may alter the concentrations of neuroactive steroids in patient s suffering from a major depressive episode. Method: In the first stud y, eight drug-native outpatients with major depression were studied du ring treatment with fluoxetine. In a complementary study, 11 inpatient s with major depression were studied during a severe depressive episod e and after recovery following treatment with different antidepressant s. Plasma samples were quantified for neuroactive steroids by means of a highly sensitive and specific combined gas chromatography/mass spec trometry analysis. Results: During depression, there tons a significan t ;decrease in 3 alpha, 5 alpha-tetrahydroprogesterone (3 alpha, 5 alp ha-THP) and 3 alpha, 5 beta-THP concentrations, both of which are posi tive modulators of the gamma-aminobutyric acid(A) receptor, and a conc omitant increase in 3 beta, 5 alpha-THP levels. This dysequilibrium of neuroactive steroids could be corrected by treatment with different a ntidepressants. Conclusions: These results provide the first clinical evidence of a possible role of neuroactive steroids in successful anti depressant therapy.