European psychiatry : the journal of the Association of European Psychiatrists · 2026
Definition of treatment-resistant late-life depression: Conclusions from a European Task Force Delphi process.
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Pozuelo Moyano B, von Gunten A, Mueller C, Yaman-Deveci R, Howard R, Stewart R, Young A H, Costello H, Bulteau S, Calvet B, Bonin-Guillaume S, Hoertel N, Robert G-H, Roche J, Lepetit A, de la Chapelle S Louchart, Agüera-Ortiz L F, Pla-Vidal J, Bouckaert F, Oude Voshaar R C, Fernandes L, Vasiliu O, Dominiak M, Priller J, Preisig M, Triolo F, Belvederi Murri M, Aakhus E, Ranjbar S, Swierkosz-Lenart K, Orgeta V, Vandel P
Аннотация
BACKGROUND: Treatment-Resistant Late-Life Depression (TRLLD) represents a significant clinical and research challenge. Studies on TRLLD use heterogeneous diagnostic criteria limiting the interpretation of results and the development of clinical guidelines.This study aimed 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.
METHODS: We conducted an electronic Delphi study with 30 European experts to identify key definitional elements of TRLLD. In the 1st survey round (SR), participants responded to open-ended questions on definitions of TRLLD. Responses informed the development of 70 structured items for 2nd 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 3rd 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 developed from consensus items.
CONCLUSION: This study provides the first European consensus definition of TRLLD and highlights the need for age-adapted diagnostic criteria that reflect the clinical complexity of depression in older adults.
METHODS: We conducted an electronic Delphi study with 30 European experts to identify key definitional elements of TRLLD. In the 1st survey round (SR), participants responded to open-ended questions on definitions of TRLLD. Responses informed the development of 70 structured items for 2nd 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 3rd 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 developed from consensus items.
CONCLUSION: This study provides the first European consensus definition of TRLLD and highlights the need for age-adapted diagnostic criteria that reflect the clinical complexity of depression in older adults.