As the title already announces this paper investigates a special group of patients: patients with so-called difficult to treat depression (DTD). One intention of this paper is to demonstrate the need for and the advantages of interdisciplinary research, on how to cross borders of different treatment approaches as well as research approaches. The other aim is to draw attention to the perspective of patients with refractory depression, some factors that have an impact on the maintenance of the depressive state and on the immense amount of suffering of these patients.