AI applied to Saudi Arabia higher education: systematic literature review-SLR with PRISMA and VOSviewer.

Treatment-resistant depression (TRD), including both unipolar and bipolar depression, remains a major clinical and public health challenge. Beyond the well-known operational definition based on failure of two successive adequate antidepressant trials, TRD is increasingly conceptualized as a dynamic, episode-spanning phenotype, shaped by symptom heterogeneity, comorbidity, and treatment history, and best captured through longitudinal staging and measurement-based care, or as Difficult-to-Treat Depression (DTD), which is defined as depression that continues to cause significant burden despite normal treatment efforts (, ). Building on the first Research Topic dedicated to TRD epidemiology, clinical features, burden, and treatment (3), this Volume II aimed to consolidate multidisciplinary contributions spanning population-level burden, clinical characterization, and emerging pharmacological and non-pharmacological interventions. The twelve articles collected in this Research Topic illustrate the need to approach TRD along a continuum: from upstream determinants and health-system constraints, to refined phenotyping and staging, to a broader therapeutic armamentarium that includes optimization of antidepressant strategies, rapid-acting agents, neuromodulation, and psychosocial care, while keeping functional outcomes and quality of life as central endpoints ().