Defining treatment-resistant bipolar depression: recommendations from the ISBD Task Force
Author(s)
Type
Journal Article
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.
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.
Date Issued
2025-09-01
Date Acceptance
2025-07-30
Citation
Bipolar Disorders: an international journal of psychiatry and neurosciences, 2025, 27 (6), pp.411-423
ISSN
1398-5647
Publisher
Wiley
Start Page
411
End Page
423
Journal / Book Title
Bipolar Disorders: an international journal of psychiatry and neurosciences
Volume
27
Issue
6
Copyright Statement
© 2025 The Author(s). Bipolar Disorders published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Publication Status
Published
Date Publish Online
2025-08-13