Time course of hypothalamic-pituitary-adrenocortical axis activity during treatment with reboxetine and mirtazapine in depressed patients.
BACKGROUND
In healthy subjects, cortisol and ACTH secretion are acutely stimulated by reboxetine and inhibited by mirtazapine. However, it was not investigated so far whether reboxetine and mirtazapine may also differ in their impact on hypothalamic-pituitary-adrenocortical (HPA) axis activity in depressed patients and whether these effects are related to clinical outcome.


OBJECTIVE
In the present study, we investigated the impact of 5-week treatment with reboxetine or mirtazapine on the combined dexamethasone suppression/corticotropin releasing hormone (DEX/CRH) test results in depressed patients.


METHODS
Forty drug-free patients suffering from a major depressive episode (Diagnostic and Statistical Manual of Mental Disorders-IV criteria) were treated with either reboxetine (8 mg/day; n=20) or mirtazapine (45 mg/day; n=20) for 5 weeks. Before, after 1 and 5 weeks of therapy, the DEX/CRH test was performed and cortisol and ACTH concentrations were measured.


RESULTS
During reboxetine treatment, a gradual and significant reduction in HPA axis activity as measured by the DEX/CRH test was seen, which was most pronounced after 5 weeks of treatment. In contrast, mirtazapine significantly reduced the cortisol and ACTH concentrations during the DEX/CRH test within 1 week. However, after 5 weeks of mirtazapine treatment, the cortisol and ACTH responses to the DEX/CRH test partially increased again both in responders and nonresponders.


CONCLUSIONS
This is the first study demonstrating differential effects of various antidepressants on the time course of serial DEX/CRH test results in depressed patients.
Schüle
Cornelius
C
Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University of Munich, Nussbaumstr 7, Munich, 80336, Germany. Cornelius.Schuele@med.uni-muenchen.de
Baghai
Thomas C
TC
Eser
Daniela
D
Zwanzger
Peter
P
Jordan
Martina
M
Buechs
Renate
R
Rupprecht
Rainer
R
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003346:Corticotropin-Releasing Hormone; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy*; D003907:Dexamethasone; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use*; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011569:Psychiatric Status Rating Scales; D000077593:Reboxetine; D013997:Time Factors
D000928:Antidepressive Agents; D005938:Glucocorticoids; D009025:Morpholines; D008803:Mianserin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D000077593:Reboxetine; D000078785:Mirtazapine; D006854:Hydrocortisone