RATIONALE: 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. OBJECTIVES: 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.
RCT Entities:
RATIONALE: 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. OBJECTIVES: 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 depressedpatients and new pharmacological approaches such as CRH(1) receptor antagonists.
Authors: Cornelius Schüle; Thomas C Baghai; Daniela Eser; Peter Zwanzger; Martina Jordan; Renate Buechs; Rainer Rupprecht Journal: Psychopharmacology (Berl) Date: 2006-04-22 Impact factor: 4.530
Authors: Cornelius Schüle; Thomas Baghai; Peter Zwanzger; Robin Ella; Daniela Eser; Frank Padberg; Hans-Jürgen Möller; Rainer Rupprecht Journal: Psychopharmacology (Berl) Date: 2003-01-28 Impact factor: 4.530
Authors: Luiz Augusto Casulari; Lucas Faria de Castro; Iruena Moraes Kessler; José Luiz Mendonça; Maria de Fátima Magalhães Gonzaga Journal: J Med Case Rep Date: 2019-06-16
Authors: Cornelius Schüle; Thomas C Baghai; Daniela Eser; Sibylle Häfner; Christoph Born; Sascha Herrmann; Rainer Rupprecht Journal: PLoS One Date: 2009-01-29 Impact factor: 3.240