title: Effects of combination treatment with mood stabilizers and mirtazapine on plasma concentrations of neuroactive steroids in depressed patients.
abstract: Antidepressants such as SSRIs or mirtazapine have been demonstrated to increase the concentrations of 3alpha-reduced neuroactive steroids throughout several weeks of treatment. However, no data are available on the impact of mood stabilizers such as lithium or carbamazepine on neuroactive steroid levels in depressed patients. Study 1 was performed in 26 drug-free depressed inpatients who were treated with either mirtazapine monotherapy (n=13) or combination therapy with mirtazapine and addition of lithium (n=13). Twenty drug-free depressed inpatients were included in study 2, receiving either mirtazapine monotherapy (n=10) or combination treatment with mirtazapine and carbamazepine (n=10). Plasma samples were taken weekly at 0800 h in the morning and quantified for neuroactive steroids by means of combined gas chromatography/mass spectrometry analysis. In study 1, the mirtazapine-induced rises in 3alpha,5alpha-tetrahydroprogesterone and 3alpha,5beta-tetrahydroprogesterone were abolished by additional lithium administration, as compared to mirtazapine monotherapy. In study 2, the mirtazapine-evoked increase in 3alpha,5alpha-tetrahydroprogesterone was reversed after additional administration of carbamazepine, presumably due to lowered mirtazapine levels after induction of cytochrome P450 enzymes. Apparently, the mood stabilizers lithium and carbamazepine do not enhance but rather reverse the increase in plasma concentrations of 3alpha-reduced neuroactive steroids in depressed patients pretreated with antidepressants such as mirtazapine.
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University, Nussbaumstr. 7, 80336 Munich, Germany. Cornelius.Schuele@med.uni-muenchen.de
authors.forename: Cornelius
authors.initials: C
authors.lastname: Schüle
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Baghai
authors.forename: Flavia
authors.initials: F
authors.lastname: di Michele
authors.forename: Daniela
authors.initials: D
authors.lastname: Eser
authors.forename: Augusto
authors.initials: A
authors.lastname: Pasini
authors.forename: Markus
authors.initials: M
authors.lastname: Schwarz
authors.forename: Rainer
authors.initials: R
authors.lastname: Rupprecht
authors.forename: Elena
authors.initials: E
authors.lastname: Romeo
mesh_terms: D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology; D003863:Depression / Q000097:blood* / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D018020:Lithium Compounds / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008803:Mianserin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008875:Middle Aged; D000078785:Mirtazapine; D011280:Pregnanolone / Q000031:analogs & derivatives / Q000097:blood; D011374:Progesterone / Q000031:analogs & derivatives / Q000097:blood; D013256:Steroids / Q000097:blood*; D014149:Tranquilizing Agents / Q000008:administration & dosage* / Q000494:pharmacology*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D018020:Lithium Compounds; D013256:Steroids; D014149:Tranquilizing Agents; D008803:Mianserin; D011374:Progesterone; D000078785:Mirtazapine; D011280:Pregnanolone