A placebo-controlled study of sertraline’s effect on cortisol response to the dexamethasone/corticotropin-releasing hormone test in healthy adults

Abstract

The dexamethasone/corticotropin-releasing hormone (Dex/CRH) test is a neuroendocrine probe involving serial blood sampling of cortisol during a standardized pharmacological challenge without inducing psychological distress in humans. Some past studies in depressed patients have shown a "normalization" or decrease in cortisol response to the Dex/CRH test following successful treatment with an antidepressant. Studies in nondepressed healthy adult samples have also shown aberrant cortisol reactivity to be associated with depression risk factors. These findings prompted research into the use of the Dex/CRH test as a tool for developing antidepressant drugs. In this study, the Dex/CRH test was evaluated with regard to its potential utility for drug development in nonclinical samples. The Dex/CRH test was administered before and after 6 weeks of blinded treatment with either sertraline 100 mg/day or matching placebo in 22 healthy adults (13 women, nine men). Cortisol response to the Dex/CRH test increased following treatment with standard doses of sertraline, compared to placebo, after controlling for age and sex. The observed pattern of change contrasts with results from published studies in depressed patients and with our initial hypothesis.