The influence of mirtazapine on anterior pituitary hormone secretion in healthy male subjects.
BACKGROUND
Unlike other antidepressants, mirtazapine does not inhibit the reuptake of norepinephrine or serotonin but acts as an antagonist at presynaptic alpha(2) receptors, at postsynaptic 5-HT(2) and 5-HT(3) receptors, and at histaminergic H(1) receptors. This special mechanism of action may be characterized by a distinct pharmacoendocrinological profile.


OBJECTIVE
In the present investigation the influence of acute oral administration of 15 mg mirtazapine on the cortisol (COR), corticotropin (ACTH), growth hormone (GH), and prolactin (PRL) secretion was examined in six healthy male subjects, compared to placebo.


METHODS
After insertion of an intravenous catheter, both the mean arterial blood pressure (MAP) and the heart rate were recorded and blood samples were drawn 1 h prior to the administration of mirtazapine or placebo (7:00 a.m.), at time of application (8:00 a.m.), and thereafter every hour up to 8:00 p.m. Concentrations of COR, ACTH, GH, and PRL were measured in each blood sample by double-antibody radioimmunoassay and chemiluminescence immunoassay methods. The area under the curve (AUC) was used as parameter for the COR, ACTH, GH, and PRL response. Furthermore, the urinary free cortisol excretion (UFC) was determined beginning at 8:00 a.m. (time of application of placebo or mirtazapine) up to 8:00 a.m. the day after.


RESULTS
Multivariate analyses of variance revealed significantly lower COR AUC, ACTH AUC, and UFC values after 15 mg mirtazapine compared to placebo, whereas no differences were found with respect to GH and PRL stimulation, MAP, and heart rate.


CONCLUSIONS
Since the acute inhibition of COR secretion in the healthy volunteers was paralleled by a simultaneous decrease of ACTH release, central mechanisms (for example, inhibition of hypothalamic CRH output) are suggested to be responsible for the inhibitory effects of mirtazapine on COR secretion. Our results are of particular interest in the light of the hypercortisolism observed in depressed patients and new pharmacological approaches such as CRH(1) receptor antagonists.
Department of Psychiatry, Ludwig-Maximilian-University, Nussbaumstrasse 7, 80336 Munich, Germany. Cornelius.Schuele@psy.med.uni-muenchen.de
Cornelius
C
Schüle
Thomas
T
Baghai
Josefine
J
Goy
Martin
M
Bidlingmaier
Christian
C
Strasburger
Gregor
G
Laakmann
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D008297:Male; D008803:Mianserin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000078785:Mirtazapine; D010908:Pituitary Hormones, Anterior / Q000378:metabolism*; D011388:Prolactin / Q000097:blood
D000929:Antidepressive Agents, Tricyclic; D010908:Pituitary Hormones, Anterior; D008803:Mianserin; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D000078785:Mirtazapine; D006854:Hydrocortisone