5HT1A-mediated stimulation of cortisol release in major depression: use of non-invasive cortisol measurements to predict clinical response.

The purpose of the present study was to explore 5HT1A-mediated cortisol release in major depressive disorder (MDD) patients in order to determine whether the degree of 5HT1A-receptor sensitivity can predict response to treatment with selective serotonin reuptake inhibitors (SSRIs). We examined whether the sensitivity of the 5HT1A receptor, as measured by the difference in salivary cortisol levels immediately before and 90 min following the administration of a single dose of the 5HT1A-selective agonist buspirone, predicted treatment outcome following an 8-week, fixed-dose, open trial of the SSRI escitalopram in 17 outpatients with MDD. Change in cortisol levels before and 90 min after the administration of buspirone were not found to predict treatment outcome, whether defined as clinical response (50% or greater reduction in symptom severity), or remission of symptoms. In conclusion, in the present study, we did not find that the change in salivary cortisol levels following the administration of a 5HT1A-selective agonist predicted treatment outcome following an 8-week, fixed-dose, open-label trial of the SSRI escitalopram among outpatients with MDD. Although the 5HT1A-desensitization hypothesis is still a valid one, the results of the present study could not provide any evidence in support.