Bipolar disorder is a complex and often debilitating illness that affects 1–2% of the global population. Among its challenges, bipolar depression stands out as the leading cause of disability, poor quality of life, and increased suicide risk. While several medications are approved for bipolar depression, a substantial proportion of patients do not respond adequately. This group is often described as having treatment-resistant bipolar depression (TRBD)—yet, until now, no universally accepted definition has existed.
A recent consensus paper by the International Society for Bipolar Disorders (ISBD) Task Force has taken an essential step toward standardizing how we define and approach TRBD.
Why a Definition Matters
Unlike unipolar depression, where treatment resistance is typically defined as non-response to two antidepressant trials, bipolar depression is more complex. Antidepressants are controversial in bipolar disorder, particularly as monotherapy, and the illness requires mood-stabilizing strategies. The lack of a standardized definition of TRBD has made it difficult to compare research findings, design clinical trials, and guide treatment development.
A consensus definition not only supports clinical clarity but also shapes research, regulatory decisions, and eventually, patient care.
The ISBD Task Force Definition
The Task Force—composed of 25 international experts—reviewed the literature, clinical trial data, and guidelines to reach consensus. They propose that TRBD should be defined as the failure to achieve a significant and sustained clinical response after at least two approved pharmacological treatments, at an adequate dose and duration, with verified adherence.
Approved Treatments Considered:
This operational definition mirrors approaches used in major depression but is adapted to the unique pharmacology of bipolar disorder.
Management Implications
Once TRBD is confirmed, treatment strategies extend beyond first-line pharmacotherapy:
Looking Ahead
The ISBD Task Force acknowledges that this definition is primarily intended for clinical trials and research standardization. In real-world practice, clinicians often rely on additional strategies, including off-label use of lithium, lamotrigine, and valproate, which remain cornerstones of bipolar depression treatment.
The consensus is a foundational step—not the final word. Future efforts will aim to integrate clinical realities, biological insights, and patient-centered outcomes into more nuanced definitions and treatment frameworks.
Key Takeaway
By adopting a standardized definition of treatment-resistant bipolar depression, researchers and clinicians can work with greater precision and consistency. This effort by the ISBD Task Force represents an essential milestone in addressing one of the most pressing unmet needs in psychiatry: developing effective, evidence-based strategies for patients who continue to suffer from the heavy burden of bipolar depression despite treatment.
Reference
Vieta E, McIntyre RS, Suppes T, et al. Defining Treatment-Resistant Bipolar Depression: Recommendations from the ISBD Task Force. Bipolar Disorders. 2025. doi: 10.1111/bdi.70048
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