Mirtazapine decreases stimulatory effects of reboxetine on cortisol, adrenocorticotropin and prolactin secretion in healthy male subjects

Reboxetine is a selective noradrenaline reuptake inhibitor, whereas
mirtazapine acts as an antagonist at noradrenergic alpha(2),
serotonin (5-HT2), 5-HT3 and histamine H-1 receptors. In a former
study we could demonstrate an inhibitory impact of mirtazapine on
cortisol secretion. In the present investigation, the influence of
combined administration of 15 mg mirtazapine and 4 mg reboxetine on
the cortisol ( COR), adrenocorticotropin ( ACTH), growth hormone
(GH), and prolactin (PRL) secretion was examined in 12 healthy male
subjects, compared to reboxetine alone ( 4 mg). In a randomized
order, the subjects received reboxetine ( 4 mg) alone or the
combination of reboxetine ( 4 mg) and mirtazapine ( 15 mg) at 8: 00
a. m. on two different days. After insertion of an intravenous
catheter, blood samples were drawn 1 h prior to the administration
of single reboxetine or the combination ( reboxetine and
mirtazapine), at time of administration, and during the time of 5 h
thereafter in periods of 30 min. Serum concentrations of COR, GH,
and PRL as well as plasma levels of ACTH were determined in each
blood sample by means of double antibody RIA, fluoroimmunoassay and
chemiluminescence immunometric assay methods. The area under the
curve (AUC) was used as parameter for the COR, ACTH, GH, and PRL
response. For statistical evaluation, the Wilcoxon signed-ranks
test was performed. There was a pronounced stimulation of COR,
ACTH, GH, and PRL concentrations after single administration of
reboxetine. When reboxetine was given in combination with
mirtazapine, a significant reduction of the COR, ACTH, and PRL
stimulation was observed whereas GH secretion patterns remained
unchanged, compared to single administration of reboxetine.
Apparently, the stimulatory effects of reboxetine on pituitary
hormone secretion via noradrenergic mechanisms are counteracted in
part by the alpha(2)-blocking properties of mirtazapine and its
inhibitory influence on cortisol secretion. Copyright (C) 2004 S.
Karger AG, Basel.