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The hypothalamic-pituitary-adrenocortical (HPA) system is believed to play an important role in the pathophysiology of major depressive disorder. In this context, the atypical antipsychotic quetiapine (QUE) has been shown to inhibit HPA system activity in healthy subjects. In this study we investigated whether the putative inhibitory effects of QUE on HPA system activity may contribute to its antidepressant efficacy. We analyzed the effects of QUE as an augmentation to the selective serotonin reuptake inhibitor (SSRI) escitalopram (ESC) on HPA system activity in comparison to a monotherapy with ESC in relation to the antidepressant effectiveness. HPA axis activity (cortisol and ACTH) was measured by means of the dexamethasone/corticotropin-releasing hormone (DEX/CRH) test which was performed before (week 0) and during (week 1, week 5) antidepressant psychopharmacotherapy. The combination therapy, but not the ESC monotherapy showed significantly inhibiting effects on HPA system activity leading to stepwise down-regulation. ACTH concentrations were reduced in the ESC/QUE group during five weeks of treatment. The inhibitory effect of QUE maybe involved in its antidepressant effects as an augmentation strategy., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: In this study, the impact of quetiapine fumarate extended release (QXR) and escitalopram (ESC) on HPA axis activity was investigated in depressed patients in relationship to antidepressant efficacy., Methods: In a randomized, open-label 5-week trial 60 inpatients suffering from major depression (DSM-IV criteria) were treated for 5 weeks with either QXR (300 mg/day) or ESC (10mg/day). The dexamethasone/CRH (DEX/CRH) test was performed before treatment, after 1, and after 5 weeks of treatment. Cortisol (COR) AUC values were used to assess HPA axis function. The Hamilton Depression Rating Scale was used weekly to estimate antidepressant efficacy., Results: QXR and ESC showed comparable antidepressant effects but strongly differed in their impact on HPA axis activity. In the QXR group, a marked inhibition of COR AUC levels was observed which was most pronounced after one week of treatment but showed a partial re-increase after 5 weeks of treatment. In contrast, ESC transiently stimulated COR AUC values (week 1) whereas COR AUC levels at week 0 and week 5 were comparable. COR improvement at week 1 (defined as COR peak value reduction between DEX/CRH test 1 and 2) was significantly associated with better clinical outcome., Conclusion: Apparently, different effects on HPA axis activity reflect distinct pharmacoendocrinological properties of psychotropic drugs., (Copyright © 2013 Elsevier Ltd. All rights reserved.)