ABSTRACT
Depression is a prevalent mental disorder that can have severe impacts. Despite medical efforts, some individuals develop treatment-resistant depression (TRD) or difficult-to-treat depression (DTD). TRD includes those unresponsive to standard treatments, whereas DTD encompasses a broader range of factors affecting treatment outcomes. This article examines the distinctions between TRD and DTD, highlighting the need for personalized multidisciplinary approaches. It discusses various therapeutic options, including pharmacological, psychological, and neurostimulation therapies, emphasizing the significance of considering psychosocial factors and individualized care. Raising awareness among the public, experts, and clinicians about the importance of psychosocial and multidisciplinary aspects in managing DTD can help reduce the stigma associated with depression and improve patient quality of life.