Defining Treatment‐Resistant Bipolar Depression: Recommendations From the <scp>ISBD</scp> Task Force
Eduard Vieta, Roger S. McIntyre, Trisha Suppes, Tamsyn E. Van Rheenen, Balwinder Singh, Kamilla Woznica Miskowiak, Allan H. Young, Lakshmi N. Yatham, Kyooseob Ha, Michael Berk, Holly A. Swartz, Chantal Henry, Maja Pantović-Stefanović, Gerard Anmella, Ayşegül Özerdem, Wiesław Jerzy Cubała, Diego Hidalgo‐Mazzei, Mauricio Tohen, Isabella Pacchiarotti, Paula Villela Nunes, Carlos López‐Jaramillo, Ana González‐Pinto, Paolo Brambilla, Robert M. Post, Jair C. Soares, Michael Bauer, Ana C. Andreazza, Xavier Justes Fradera, Montserrat Cosials-Lopez, Giovanna Fico
Abstract
OBJECTIVE: Despite the availability of approved treatments, a substantial proportion of patients with bipolar disorder experience treatment-resistant bipolar depression (TRBD), characterized by persistent depressive symptoms unresponsive to standard therapies. However, a universally accepted definition of TRBD is lacking. This consensus document, developed by the International Society for Bipolar Disorders (ISBD) Task Force on TRBD, aims to provide a standardized definition of TRBD to facilitate clinical trials, research, and treatment strategies. METHODS: The Task Force employed a literature review, clinical trials analysis, and expert consensus meetings to define TRBD. RESULTS: TRBD was defined as the failure to achieve a significant and sustained clinical response after at least two approved and adequately dosed pharmacological treatments, administered for a sufficient duration with treatment adherence. For bipolar I (BD-I) depression, approved treatments included quetiapine (300-600 mg/day for ≥ 8 weeks), lurasidone (20-120 mg/day for ≥ 6 weeks), the combination of olanzapine (6-12 mg/day) and fluoxetine (25-75 mg/day for ≥ 8 weeks), cariprazine (1.5-3 mg/day for ≥ 6 weeks), and lumateperone (42 mg/day for ≥ 6 weeks). For bipolar II (BD-II) depression, approved treatments included quetiapine (300-600 mg/day for ≥ 8 weeks) and lumateperone (42 mg/day for ≥ 6 weeks). CONCLUSION: This consensus definition aims to provide clarity for clinical trials, improve consistency in research, and guide treatment approaches and inform regulatory pathways. It represents a foundational step in addressing the unmet needs in TRBD and promoting the development of innovative therapeutic strategies. Future efforts will focus on adapting the definition to better align with real-world clinical challenges and optimize patient care.