Faculty, Staff and Student Publications

Publication Date

8-13-2025

Journal

Bipolar Disorder

DOI

10.1111/bdi.70048

PMID

40808269

PMCID

PMC12393891

PubMedCentral® Posted Date

8-29-2025

PubMedCentral® Full Text Version

Author MSS

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.

Keywords

bipolar depression, bipolar disorder, clinical trial, depression, mental health, psychiatry, treatment response, treatment-resistant bipolar depression

Published Open-Access

yes

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