Attenuation of hypothalamic-pituitary-adrenocortical hyperactivity in depressed patients by mirtazapine.
BACKGROUND
It has been suggested that hypothalamic-pituitary-adrenocortical (HPA) system dysregulation plays an important role in the pathophysiology of depression and that normalization of HPA axis hyperactivity precedes successful treatment with antidepressants. Mirtazapine acts as an antagonist at presynaptic alpha(2)-receptors and at postsynaptic 5-hydroxytryptamine (5-HT)(2), 5-HT(3) and histamine H(1) receptors. It has been shown acutely to inhibit cortisol secretion in healthy subjects.


OBJECTIVE
In this study, we investigated whether mirtazapine may downtune HPA axis hyperactivity in depressed patients and whether this is related to treatment outcome.


METHODS
Forty patients suffering from a major depressive episode (DSM-IV criteria) were treated with mirtazapine for 5 weeks. The combined dexamethasone suppression/CRH stimulation test (DEX/CRH test) was performed before and after 1 week of mirtazapine treatment (45 mg daily).


RESULTS
Mirtazapine effectively reduced the overshoot of cortisol and ACTH during the DEX/CRH test both in treatment responders and non-responders within 1 week.


CONCLUSIONS
Apparently, mirtazapine rapidly attenuates HPA axis hyperactivity in depressed patients via direct pharmacoendocrinological effects. However, this amelioration of HPA system dysregulation is not necessarily related to clinical improvement.
Schüle
Cornelius
C
Department of Psychiatry, University of Munich, Nussbaumstrasse 7, 80336, Munich, Germany. Cornelius.Schuele@psy.med.uni-muenchen.de
Baghai
Thomas
T
Zwanzger
Peter
P
Ella
Robin
R
Eser
Daniela
D
Padberg
Frank
F
Möller
Hans-Jürgen
HJ
Rupprecht
Rainer
R
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D003346:Corticotropin-Releasing Hormone; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology* / Q000523:psychology; 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 / Q000627:therapeutic use*; D000078785:Mirtazapine; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011569:Psychiatric Status Rating Scales
D000929:Antidepressive Agents, Tricyclic; D005938:Glucocorticoids; D008803:Mianserin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D000078785:Mirtazapine; D006854:Hydrocortisone