Elevated Cortisol in Older Adults With Generalized Anxiety Disorder Is Reduced by Treatment: A Placebo-Controlled Evaluation of Escitalopram

Abstract

Generalized anxiety disorder (GAD) is a common disorder in older adults, which has been linked to hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in this age group. The authors examined whether treatment of GAD in older adults with a selective serotonin reuptake inhibitor (SSRI) corrects this HPA axis hyperactivity. The authors examined adults aged 60 years and older with GAD in a 12-week randomized controlled trial comparing the SSRI escitalopram with placebo. The authors collected salivary cortisol at six daily time points for 2 consecutive days to assess peak and total (area under the curve) cortisol, both at baseline and posttreatment. Compared with placebo-treated patients, SSRI-treated patients had a significantly greater reduction in both peak and total cortisol. This reduction in cortisol was limited to patients with elevated (above the median) baseline cortisol, in whom SSRI-treated patients showed substantially greater reduction in cortisol than did placebo-treated patients. Reductions in cortisol were associated with improvements in anxiety. Additionally, genetic variability at the serotonin transporter promoter predicted cortisol changes. SSRI treatment of GAD in older adults reduces HPA axis hyperactivity. Further research should determine whether these treatment-attributable changes are sustained and beneficial.