Endocrinological effects of mirtazapine in healthy volunteers.
OBJECTIVE
Unlike other antidepressants, mirtazapine does not inhibit the reuptake of norepinephrine or serotonin (5-HT) but acts as an antagonist at presynaptic alpha2-receptors and at postsynaptic 5-HT2, 5-HT3 and histamine H1-receptors. In the present investigation, the influence of acute oral administration of 15-mg mirtazapine on the cortisol (COR), adrenocorticotropin (ACTH), growth hormone (GH) and prolactin (PRL) secretion was examined in 12 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 administration (8:00 a.m.) and during 5 h thereafter in periods of 30 min. 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; 0-300 min after mirtazapine or placebo administration) 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 administration of placebo or mirtazapine) up to 8:00 a.m. the day after.


RESULTS
Two-sided t-tests for paired samples revealed significantly lower COR AUC, ACTH AUC, UFC and PRL AUC values after 15-mg mirtazapine compared to placebo, whereas no significant differences were found with respect to GH AUC, 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 (e.g., inhibition of hypothalamic corticotropin releasing hormone (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 CRH1 receptor antagonists.
Schüle
Cornelius
C
Psychiatric Hospital, University of Munich, Munich, Germany. cornelius.schuele@psy.med.uni-muenchen.de
Baghai
Thomas
T
Bidlingmaier
Martin
M
Strasburger
Christian
C
Laakmann
Gregor
G
D000284:Administration, Oral; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001794:Blood Pressure; D003866:Depressive Disorder / Q000188:drug therapy; D004703:Endocrine System / Q000187:drug effects*; D006339:Heart Rate; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000078785:Mirtazapine; D010919:Placebos; D011388:Prolactin / Q000378:metabolism
D000929:Antidepressive Agents, Tricyclic; D010919:Placebos; D019382:Human Growth Hormone; D008803:Mianserin; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D000078785:Mirtazapine; D006854:Hydrocortisone