High-quality antidepressant discovery by understanding stress hormone physiology

Compensating the consequences of impaired corticosteroid receptor signaling is a novel strategy to discover better antidepressants. The prevailing drugs gradually improve stress hormone regulation along with ameliorating psychopathology. The current understanding of how neuropeptides, such as corticotropin-releasing hormone (CRH) and vasopressin (AVP), drive cortisol secretion via corticotrophin has paved the way for CRH- and AVP-receptor antagonists. As alternative strategies, the blockade of corticosteroid receptors or inhibition of cortisol synthesis has emerged. All these strategies are not yet fully clinically developed, but preliminary data from basic and clinical research strongly underscore that such strategies may lead to innovative treatment modalities.