Concentrations of 3 alpha-reduced neuroactive steroids are altered in depression and normalize after antidepressant pharmacotherapy with selective serotonin re-uptake inhibitors (SSRIs). We investigated the impact of mirtazapine on the activity of a key neurosteroidogenic enzyme, the 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD), and on the levels of neuroactive steroids in relation to clinical response. A total of 23 drug-free in-patients suffering from a major depressive episode (DSM-IV criteria) underwent 5-week treatment with mirtazapine (45 mg/day). Plasma samples were taken weekly at 0800 and quantified for neuroactive steroids by means of combined gas chromatography/mass spectrometry analysis. Enzyme activity was determined by assessment of steroid conversion rates. Irrespective of clinical outcome, there were significant increases in 3 alpha, 5 alpha-tetrahydroprogesterone, 3 alpha, 5 beta-tetrahydroprogesterone, 5 alpha-dihydroprogesterone, and 5 beta-dihydroprogesterone after mirtazapine treatment, whereas 3 beta, 5 alpha-tetrahydroprogesterone levels were significantly decreased. In vitro investigations demonstrated a dose-dependent inhibitory effect of mirtazapine on the activity of the microsomal 3 alpha-HSD in the oxidative direction (conversion of 3 alpha, 5 alpha-tetrahydroprogesterone to 5 alpha-dihydroprogesterone). Mirtazapine affects neuroactive steroid composition similarly as do SSRIs. The inhibition of the oxidative pathway catalyzed by the microsomal 3 alpha-HSD is compatible with an enhanced formation of 3 alpha-reduced neuroactive steroids. However, the changes in neuroactive steroid concentrations more likely reflect direct pharmacological effects of this antidepressant rather than clinical improvement in general.
Schule, C., Romeo, E., Uzunov, D.P., Eser, D., Di Michele, F., Baghai, T.C., et al. (2006). Influence of mirtazapine on plasma concentrations of neuroactive steroids in major depression and on 3 alpha-hydroxysteroid dehydrogenase activity. MOLECULAR PSYCHIATRY, 11(3), 261-272.
|Tipologia:||Articolo su rivista|
|Citazione:||Schule, C., Romeo, E., Uzunov, D.P., Eser, D., Di Michele, F., Baghai, T.C., et al. (2006). Influence of mirtazapine on plasma concentrations of neuroactive steroids in major depression and on 3 alpha-hydroxysteroid dehydrogenase activity. MOLECULAR PSYCHIATRY, 11(3), 261-272.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore MED/39 - Neuropsichiatria Infantile|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/sj.mp.4001782|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2006|
|Titolo:||Influence of mirtazapine on plasma concentrations of neuroactive steroids in major depression and on 3 alpha-hydroxysteroid dehydrogenase activity|
|Autori:||Schule, C; Romeo, E; Uzunov, DP; Eser, D; Di Michele, F; Baghai, TC; Pasini, A; Schwarz, M; Kempter, H; Rupprecht, R|
|Appare nelle tipologie:||01 - Articolo su rivista|