The effects of six-day SSRI administration on diurnal cortisol secretion in healthy volunteers.

Abstract

Rationale Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been widely reported in depression, and evidence suggests that selective serotonin reuptake inhibitors (SSRIs) might exert their therapeutic effects through altering cortisol secretion. Objective This study assessed the effects of SSRI administration on diurnal cortisol secretion in healthy volunteers. Methods Sixty-four healthy men and women were randomised to receive either 10 mg escitalopram or placebo for six days in a double-blind fashion. On day six of medication, saliva samples were obtained at home for measurement of diurnal cortisol parameters (cortisol slope, cortisol awakening response, total daily cortisol output). Results Women receiving escitalopram had significantly steeper cortisol slopes across the day compared with those receiving placebo (F(1, 36) = 7.54, p = 0.009). This alteration in cortisol slope was driven by increases in waking cortisol levels (F(1, 35) = 9.21, p = 0.005). Escitalopram did not have any significant effect on the cortisol awakening response or the total daily cortisol output. Conclusions Flattened cortisol slopes have been seen in depression. The results of this study suggest that escitalopram might exert its therapeutic effect in women in part through correction of a flattened diurnal cortisol rhythm.