Mirtazapine suppresses the increases in plasma levels of adrenocorticotropic hormone and neuropeptide Y under continual stress exposure

Some depressions are presumed to result from changes in levels of stress-related hormones released from the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS), represented by adrenocorticotropic hormone (ACTH) and neuropeptide Y (NPY), respectively. Venipuncture for blood sampling has been proposed to be a stress factor that increases circulating ACTH and NPY levels. We examined the effects of mirtazapine on plasma levels of ACTH- and NPY-like immunoreactive substances (IS) in healthy subjects under continual stress induced by repetitive venipunctures for blood sampling. An open-labeled crossover study was conducted on eight healthy volunteers. Each subject was administered a single oral dose of mirtazapine or placebo at an interval of 1 month. Venous blood samples were collected repetitively before and after each administration. Plasma levels of ACTH- and NPY-IS were measured using a highly sensitive enzyme immunoassay. In the placebo group, plasma ACTH-IS levels at 240 min and NPY-IS levels at 40 min increased significantly compared with the levels before administration, presumably due to stress. Oral administration of mirtazapine resulted in significant decreases in plasma ACTH-IS level at 60 and 240 min and NPY-IS level at 20 and 40 min compared with placebo administration. These findings suggest that the antidepressant activity of mirtazapine may involve the suppression of not only the HPA axis but also the SNS.