Changes in Hypothalamic–Pituitary–Adrenal Axis Measures After Vagus Nerve Stimulation Therapy in Chronic Depression

Abstract

Little is known about the hypothalamic-pituitary-adrenal (HPA) axis stress system in chronic depression. This study examined the corticotropin-releasing hormone (CRH) challenge test in a group of patients with chronic depression, before and after 3 months of treatment with vagus nerve stimulation (VNS) therapy, and a matched group of healthy control subjects. Key inclusion criteria were DSM-IV-defined major depressive disorder, a history of a current episode lasting for at least 2 years, and unresponsiveness to at least two classes of antidepressant medications. Eleven test subjects and 11 matched control subjects underwent a CRH challenge. There were significant reductions in depression scores over the study period. The CRH/ACTH (adrenocorticotropic hormone) responses in the depressed group before VNS implantation were significantly higher than in the healthy group and were reduced to normal values after VNS treatment. Some measures of cortisol response were elevated before treatment and were reduced to normal over the study period. The only clinical measure correlated with HPA axis alterations was reduction in atypical depressive symptom scores. These preliminary results suggest that chronic depression, in contrast to acute melancholic depression, might be characterized by increased ACTH response to CRH challenge. Short-term treatment with VNS therapy was associated with normalization of this response.