Effects of mirtazapine on growth hormone, prolactin, and cortisol secretion in healthy male subjects

In the present study the effects of acute PO-administration of 15 mg mirtaz apine on the growth hormone (GH), prolactin (PRL), and cortisol (COR) secre tion were examined in eight physically and mentally healthy male subjects, compared to placebo. Mirtazapine is a new antidepressant agent which does n ot inhibit the reuptake of norepinephrine or serotonin but is an antagonist of presynaptic and, presumably, postsynaptic alpha(2)-receptors as well as an antagonist of postsynpatic 5-HT2 and 5-HT3-receptors. After insertion o f an IV catheter, blood samples were drawn 1 h prior to the administration of mirtazapine or placebo, at time of application, and during the time of 4 h after application in periods of 30 min. Plasma concentrations of GH, PRL , and COR were determined in each blood sample by double antibody RIA metho ds. The area under the curve (AUC) value was used as parameter for the GH, PRL, and COR response. With respect to GH and PRL secretion, mirtazapine di d not show any effects in comparison with placebo. However, in all subjects , the COR concentrations were remarkably lower after mirtazapine compared t o placebo, the difference being obvious in the mean value graphs 60 min aft er the application up to the end of the measurement period. The t-test for paired samples revealed a highly significant difference (P < 0.01) in COR-A UC-values between the mirtazapine group (mean COR-AUC: 1558.07 mu g/100 mi x 240 min) and the placebo group (mean COR-AUC: 2698.86 mu g/100 mi x 240 m in). Further studies have to elucidate the question whether the demonstrate d inhibition of COR secretion after application of 15 mg mirtazapine is cau sed by central or peripheral effects of this substance. (C) 1999 Elsevier S cience Ltd. All rights reserved.