Mirtazapine Acutely Inhibits Salivary Cortisol Concentrations in Depressed Patients

ArticleinAnnals of the New York Academy of Sciences 1032(1):279-82 · January 2005with15 Reads
DOI: 10.1196/annals.1314.038 · Source: PubMed
Mirtazapine has been shown to acutely inhibit cortisol secretion in healthy subjects. In the current study, the impact of mirtazapine treatment on salivary cortisol secretion was investigated in 12 patients with major depression (DSM-IV criteria). Patients were treated with mirtazapine for 3 weeks, receiving 15 mg of mirtazapine on day 0, 30 mg on day 1, and 45 mg per day from day 2 to the end of the study (day 21). Response to mirtazapine treatment was defined by a reduction of at least 50% in the Hamilton Rating Scale for Depression after 3 weeks of therapy. Salivary cortisol concentrations were measured before treatment (day -1), at the beginning of treatment (day 0), after 1 week (day 7), and after 3 weeks (day 21) of treatment with mirtazapine. Saliva samples were collected hourly from 8 am to 8 pm. A significant reduction in cortisol concentrations was already noted after 1 day of mirtazapine treatment which was comparable in responders and in nonresponders. Mirtazapine therefore appears to be an effective in decreasing hypercortisolism in depression. However, the importance of the acute inhibitory effects of mirtazapine on cortisol secretion for its antidepressant efficacy has to be further clarified.


    • "A single dose of clomipramine increased circulating leptin more in obese than in normal-weight participants (Oppert et al., 1997), which was not associated with a corresponding decrease in cortisol. An increase in circulating levels of leptin associated with a decrease in plasma or salivary cortisol during treatment with the antidepressant mirtazapine (Kraus et al., 2002; Schule et al., 2003; Laakmann et al., 2004; Schmid et al., 2006) supported a role of leptin in reducing the activity of the HPA axis. However, cortisol secretion and leptin production did not alter significantly in depressed women following an 8-week course of citalopram, despite a considerable improvement in depression scores (Kauffman et al., 2005). "
    [Show abstract] [Hide abstract] ABSTRACT: Stress is defined as a state that can threaten homeostasis in an organism to initiate the adaptive process. Stress mediators, which include the classic neuroendocrine hormones and a number of neurotransmitters, cytokines, and growth factors, regulate both basal and threatened homeostasis to help control the stress. Severity of stress, as well as malfunctioning of stress pathways, may impair its controllability, leading to the pathogenesis of psychiatric illnesses including depression. Leptin was initially identified as an antiobesity hormone, acting as a negative feedback adiposity signal to control energy homeostasis by binding to its receptors in the hypothalamus. Accumulating evidence has expanded the function of leptin from the control of energy balance to the regulation of other physiological and psychological processes. The aim of this paper is to evaluate the potential role of leptin in stress controllability. To this end, studies on the role of leptin in stress-induced activation of the hypothalamus-pituitary-adrenocortical axis, feeding behavior, learned helplessness, and other depression models have been accumulated. The knowledge accumulated in this article may facilitate the development of alternative treatment strategies, beyond serotonin and noradrenaline reuptake inhibition, for psychiatric care and stress-related disorders.
    Full-text · Article · Jul 2014
    • "Nearly half of depressed patients are not susceptible to the negative feedback effect of dexamethasone on the hypothalamic–pituitary–adrenal axis and display abnormalities on a dexamethasone suppression test (Ribeiro et al., 1993). It is suggested that, on the one hand, the short term use of the glucocorticoid receptor antagonists could be beneficial in the treatment of mood disorders (Belanoff et al., 2002; Murphy et al., 1993; Young et al., 2004), while on the other, the administration of antidepressant therapy efficiently normalizes the disturbed cortisol circulation and its hypersecretion, which are experienced by a high percentage of depressed patients (Dinan, 2001; Laakmann et al., 2004; Pariante et al., 2003; Parker et al., 2003). Similarly, efficient treatment for hypercortisolemia in patients with Cushing's disease has led to an improvement in their depressed mood (Starkman et al., 1986). "
    [Show abstract] [Hide abstract] ABSTRACT: There is a close relationship between chronic stress, glucocorticoids and depression. Psychiatric and cognitive symptoms resembling major depression have been observed in patients experiencing elevated glucocorticoid levels, and a high percentage of people suffering from depression have undergone a stressful event/events prior to the onset of this mental disorder. In our study, we investigated whether acute and chronic treatment of dexamethasone induces depression-like behavior in mice and if dexamethasone therapy influences the activity of antidepressant drugs with diverse modes of action. The antidepressant-like effect was assessed by the forced swim test in adult mice. The depressogenic-like activity of dexamethasone turned out to be dose-dependent: only the highest tested dose of the glucocorticoid (i.e., 64μg/kg) given as a single injection increased immobility time, whereas 16μg/kg/day of dexamethasone (but not 4μg/kg/day) administered repeatedly induced a significant alteration in animal behavior. These depressogenic doses of dexamethasone (i.e., 64μg/kg and 16μg/kg/day for an acute and repeated administration, respectively) diminished the antidepressant potential of the therapeutic doses of imipramine (10mg/kg), amitriptyline (10mg/kg), tianeptine (25mg/kg), mianserin (10mg/kg), citalopram (15mg/kg) and moclobemide (25mg/kg). Two main findings of our study should be particularly underlined: (1) both single and repeated administration of dexamethasone evoked a depression-like behavior of mice, (2) both single and repeated administration of dexamethasone were able to modify the activity of the antidepressant agents from various pharmacological groups, which may lead to a considerable reduction in the efficacy of pharmacotherapy prescribed for patients with mood disorders.
    Full-text · Article · Jun 2014
    • "As a possible compensatory response to the hypercortisolism, the ratio of glucocorticoid to mineralocorticoid receptor expression appears to be lower in depressed patients (Juruena et al., 2004). Meanwhile, promising treatment effects on both HPA axis activity and mood are observed in a new class of antidepressants that are designed to reduce the amount of circulating glucocorticoids (O'Dwyer et al., 1995; Laakmann et al., 2004; Carvalho and Pariante, 2008). With respect to the serotonergic system, tph2, the gene encoding the rate-limiting enzyme for brain serotonin (5-hydroxytryptamine; 5-HT) synthesis ( Patel et al., 2004; Zhang et al., 2004), may be a reliable biomarker for MDD: levels of tph2 mRNA and protein expression consistently have been found to be elevated in depressed suicide victims, both in the brainstem dorsal raphe nucleus (DR) (Underwood et al., 1999; Boldrini et al., 2005; Bach-Mizrachi et al., 2006 Bonkale et al., 2006; Underwood et al., 2010), the main source of 5-HT in the brain, and in DR projection regions (Perroud et al., 2010). "
    Full-text · Dataset · Feb 2013 · Progress in Neuro-Psychopharmacology and Biological Psychiatry
Show more