Background
Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system is one of the best replicated pathophysiological findings in depression. However, studies on the influence of treatment on the HPA system have partly yielded inconsistent results.

Objective
To assess the effects of citalopram monotherapy on the HPA system of mainly drug naïve patients with major depression by means of the combined DEX/CRH test.

Methods
The DEX/CRH test was conducted twice in 30 patients (25 drug naïve for the index episode) with major depression (single episode or unipolar recurrent; SCID I- and II-confirmed): directly before the start of a citalopram monotherapy (day 0) and four weeks thereafter (day 28).

Results
Twenty-three patients responded (≥50% reduction in the HDRS21-score), and 17 of them also reached criteria of remission (HDRS ≤ 7). Baseline (dexamethasone-suppressed) and CRH-stimulated ACTH concentrations significantly decreased from day 0 to day 28. CRH-stimulated cortisol concentrations also fell, although not significantly, but baseline cortisol concentrations exhibited a significant increase from day 0 to day 28.

Conclusions
The blunting of the ACTH response in the DEX/CRH test under citalopram is in line with what has been observed in most studies with antidepressants. However, the partial rise in cortisol concentrations indicates an increase in the sensitivity of the adrenal cortex to ACTH. State-dependent alterations in the volume and the ACTH responsiveness of the adrenal gland have repeatedly been reported in depressed subjects, which indicates the possibility that SSRIs such as citalopram might exhibit a direct or indirect effect on the adrenal cortex.