Definition of treatment-resistant late-life depression: Conclusions from a European task force Delphi process

Introduction: Treatment-Resistant Late-Life Depression (TRLLD) represents a significant clinical and research challenge.Studies on TRLLD use heterogeneous diagnostic criteria and operational definitions, limiting interpretation of results and development of clinical guidelines.Objective: To establish expert consensus on the core components and definition of TRLLD through a Delphi process conducted by a European task force of clinicians and researchers with experience in late-life depression (LLD).Methods: We conducted an electronic Delphi study with 30 European experts to identify key definitional elements of TRLLD.In the 1 st survey round (SR), participants responded to openended questions on definitions of TRLLD.Responses informed the development of 70 structured items for 2 nd SR, involving 58 closed (yes/no) items and 12 multiple-choice questions across six domains: symptom presentation, cognitive impairment, comorbidities, pharmacotherapy, treatment adherence, and psychosocial factors.Consensus was defined as ≥70% agreement.In 3 rd SR, participants reviewed comments and validated the final categorical definition, the operational staging model and the derived decision algorithm for TRLLD.Results: Consensus was reached for 72.4% of the 58 closed items.Experts agreed that the categorical definition of TRLLD should correspond to major depressive disorder in individuals aged ≥65 years who show insufficient response to two adequate antidepressant treatments, in the absence of dementia and medical conditions that could account for depressive symptoms.An operational staging model and decision-making algorithm were also developed from consensus items.