Quetiapine Prolong, Escitalopram and Hypothalamic-pituitary-adrenocortical (HPA) Axis Activity in Depressed Patients
Status:
Completed
Trial end date:
2012-02-01
Target enrollment:
Participant gender:
Summary
In former studies of the investigators research group the investigators could also
demonstrate acute inhibitory effects of the antidepressant mirtazapine on ACTH and cortisol
release in normal controls (Schüle et al. 2002), most likely mediated via antagonism at
central 5-HT2- and H1-receptors. In contrast to mirtazapine, serotonin or norepinephrine
reuptake inhibiting antidepressants acutely stimulate ACTH and cortisol secretion (Schüle
2007). The investigators also performed a study in depressed patients who were treated either
with mirtazapine or with reboxetine using serial dexamethasone/CRH tests (week 0, 1, and 5)
as a parameter for HPA axis activity. Mirtazapine, but not the norepinephrine reuptake
inhibitor reboxetine was able to significantly reduce HPA axis activity already within one
week (Schüle et al. 2006). Mirtazapine is known to have an earlier onset of antidepressant
action than do SSRIs such as sertraline (Behnke et al. 2003) or antidepressants with dual
mechanism of action such as venlafaxine (Benkert et al. 2006), possibly due to its rapid
inhibition of HPA axis activity in unipolar depressed patients.
Since mirtazapine and quetiapine have similar effects on the HPA system in healthy male
volunteers (i.e. inhibition of ACTH and cortisol secretion), a rapid attenuation of HPA axis
activity is also expected during quetiapine XR treatment in depressed patients.
Therefore, in the present study the investigators goal is to investigate whether quetiapine
fumarate XR at a dosage of 300 mg per day has an impact on HPA axis activity in unipolar
depressed patients, as measured by serial dexamethasone/CRH tests (week 0, 1, and 5) and
salivary cortisol profiles and whether putative effects of quetiapine XR on the HPA system
are related to its antidepressant efficacy.