Time course of hypothalamic-pituitary-adrenocortical axis activity during treatment with reboxetine and mirtazapine in depressed patients

Schüle, Cornelius; Baghai, Thomas C.; Eser, Daniela; Zwanzger, Peter; Jordan, Martina; Buechs, Renate; Rupprecht, Rainer

doi:10.1007/s00213-006-0382-7

Cited by 56 publications

(38 citation statements)

References 53 publications

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“…Schule and colleagues reported recently that 5-week treatment with reboxetine in depressed patients was associated with reductions in HPA axis function, assessed using the dexamethasone suppression/corticotropin releasing hormone test. Mirtazapine, an antagonist of noradrenergic and serotonergic sub-receptors, exerted more complex effects (Schule et al, 2004;Schule et al, 2006). Consequentially, it is likely but has yet to be Figure 1 The effects of atomoxetine and citalopram on cardiovascular measures Note *p < 0.05 atomoxetine-treated group showed significantly higher pulse rate than placebo (LSD tests following significant ANOVA).…”

Section: Discussionmentioning

confidence: 94%

Atomoxetine increases salivary cortisol in healthy volunteers

et al. 2007

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It has been proposed that acute hypothalamo-pituitary-adrenal (HPA) axis challenge using noradrenergic drugs may be of utility in assessing the functional integrity of central noradrenaline pathways. Atomoxetine (formerly tomoxetine) is a highly selective noradrenaline reuptake inhibitor, which has recently been licensed for the treatment of attention deficit hyperactivity disorder (ADHD). The aim of this study was to assess the effects of acute atomoxetine on salivary cortisol levels for the first time.A total of 60 healthy male volunteers received 60 mg atomoxetine, 30 mg citalopram, or placebo per os in a double-blind parallel groups design (n = 20 per group). Salivary cortisol, blood pressure and pulse rates were recorded at baseline and at +1.0, +1.5, +2.5 and +3.5 hours after capsule administration.60 mg atomoxetine led to highly significant increases in salivary cortisol and a moderate increase in pulse rate, in the absence of significant effects on blood pressure. 30 mg citalopram had no significant effects on cortisol or cardiovascular parameters. These data support the utility of atomoxetine neuroendocrine challenge for evaluating central noradrenaline pathways, which may be of future use in neuropsychiatric patient studies. Furthermore, the effects of atomoxetine on HPA axis function may have clinical implications given the use of this agent in the treatment of ADHD.

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Section: Discussionmentioning

confidence: 94%

Atomoxetine increases salivary cortisol in healthy volunteers

et al. 2007

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“…This could contribute to the hippocampal volume reductions seen in depression (McEwen 2007). Chronic antidepressant treatment in humans has been shown to decrease HPA activity, significantly reducing the concentrations of cortisol and ACTH, in serum and plasma, respectively (Mason and Pariante 2006;Schüle et al 2006).…”

Section: Discussionmentioning

confidence: 97%

Depressive-Like Parameters in Sepsis Survivor Rats

et al. 2009

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The inflammatory and immune responses evoked in sepsis may create not only an acute brain dysfunction, which occurs in the majority of septic patients, but also long-term deficits such as memory impairment. In this context, we evaluated depressive-like parameters in sepsis survivor rats. For this purpose, male Wistar rats, weighing 300-350 g, underwent cecal ligation and perforation (CLP) (sepsis group) followed by "basic support", or were sham-operated (control group). After 3 days of the sepsis procedure, the animals were treated with imipramine at 10 mg/kg or saline during 14 days (days 3-17). The consumption of sweet food was measured for 7 days (days 10-17) and the body weight was measured before CLP, 10, and 17 days after CLP. Seventeen days after sepsis (immediately after sweet food consumption measurement), the animals were anesthetized and blood was withdrawn for the analyses of corticosterone and adrenocorticotropic hormone (ACTH) levels, and immediately killed by decapitation. The adrenal gland and hippocampus were immediately isolated and weighed, and the hippocampus was utilized for determining brain-derived neurotrophic factor (BDNF) levels. It was observed that animals subjected to CLP presented decreased sucrose intake. Septic rats did not increase body weight and presented an increase in the weight of adrenal gland. Both corticosterone and ACTH levels were increased, while hippocampus weight and BDNF levels in the hippocampus decreased. The treatment with imipramine reversed all the parameters described above. Our results supported the hypothesis that rats that survive sepsis show depressive-like behavior, alterations in the hypothalamus-pituitary-adrenal axis, and decreased BDNF levels in the hippocampus.

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“…These agents reportedly reduce the sensitivity of CRH neurons in the PVN as well (Stout et al, 2002) and cortisol levels return to normal in depressed patients treated with a variety of antidepressants (Himmerich et al, 2006;Schule et al, 2006).…”

Section: Discussionmentioning

confidence: 98%

Ovarian Steroid Treatment Decreases Corticotropin-Releasing Hormone (CRH) mRNA and Protein in the Hypothalamic Paraventricular Nucleus of Ovariectomized Monkeys

Bethea

Centeno

2007

Neuropsychopharmacol

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Corticotropin-releasing hormone (CRH) gene and protein expression were examined in the paraventricular nucleus (PVN) of ovariectomized female macaques treated with placebo or hormone therapy (HT) consisting of either estrogen (E) for 28 days, or progesterone (P) for the last 14 of 28 days, or E for 28 days supplemented with P for the last 14 of 28 days using Silastic capsules implanted s.c. in the periscapular region (n ¼ 4/group). Perfusion fixed sections (25 mm) at five levels of the PVN (rostral to caudal at 250 mm intervals) were immunostained (ICC) with an antibody to human CRH or processed in an in situ hybridization (ISH) assay with a monkey specific CRH riboprobe. The immunostained CRH-positive area was quantified with a Marianas Stereology Workstation and Slidebook 4.2. There was a significant decrease in the immunological CRH signal with E, P, and E + P treatment as measured by total or average pixels and microns (analysis of variance (ANOVA), po0.002; Student-Newman-Keul's post hoc test versus placebo control group, po0.05). There was also a decrease in the number of detectable CRH neurons (ANOVA, po0.03) with HT. The sections processed for ISH were exposed to autoradiographic films. The CRH mRNA signal was analyzed with NIH Image. The average optical density and positive pixel area of the CRH mRNA signal was significantly suppressed by ovarian HT (ANOVA po0.002; StudentNewman-Keul's post hoc test versus placebo control group, po0.05). In summary, 1 month of stable treatment with a moderate dose of E, P or E + P significantly reduced CRH mRNA and protein in the PVN of ovariectomized monkeys. These results suggest that this hormone treatment regimen may increase stress resilience in surgically menopausal primates.

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Time course of hypothalamic-pituitary-adrenocortical axis activity during treatment with reboxetine and mirtazapine in depressed patients

Abstract: This is the first study demonstrating differential effects of various antidepressants on the time course of serial DEX/CRH test results in depressed patients.

Cited by 56 publications

References 53 publications

Atomoxetine increases salivary cortisol in healthy volunteers

Atomoxetine increases salivary cortisol in healthy volunteers

Depressive-Like Parameters in Sepsis Survivor Rats

Ovarian Steroid Treatment Decreases Corticotropin-Releasing Hormone (CRH) mRNA and Protein in the Hypothalamic Paraventricular Nucleus of Ovariectomized Monkeys

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