Four days of citalopram increase suppression of cortisol secretion by prednisolone in healthy volunteers

Rationale: Chronic antidepressant treatment increases glucocorticoid-mediated negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis, and thus reduces HPA axis activity, in depressed patients and healthy controls. In contrast, acute antidepressant treatment induces an activation of basal HPA axis activity. Objectives: We examined the effects of 4 days of treatment with the selective serotonin reuptake inhibitor, citalopram, on basal salivary cortisol and on suppression of salivary cortisol by prednisolone. Methods: We used a single-blind, placebo-controlled, repeated-measure design. Salivary cortisol was measured from 0900 to 1700 hours. In the first phase of the study, basal salivary cortisol secretion was measured on 2 study days, before and after 4 days of treatment with citalopram ( orally, 20 mg/day). In the second phase, salivary cortisol secretion after suppression by prednisolone ( 5 mg, given at 2200 hours the night before) was measured on 2 study days, again before and after 4 days of treatment with citalopram ( orally, 20 mg/ day). Eight volunteers participated to the study. Results: Citalopram increased basal salivary cortisol in the morning ( 0900 - 1100 hours) by approximately 47% ( P = 0.003). Moreover, citalopram increased suppression by prednisolone in the morning ( 0900 - 1100 hours): suppression was approximately 22% before citalopram and 45% after citalopram (P = 0.05). Conclusions: Citalopram increases glucocorticoid-mediated negative feedback on the HPA axis after as little as 4 days of treatment. This effect could be due to an increased function of the corticosteroid receptors. Our findings further support the notion that one of the mechanisms by which antidepressants exert their therapeutic effects is by normalizing HPA axis hyperactivity in depressed patients.