Treatment-resistant bipolar depression is a common clinical problem. Unfortunately, in comparison with treatment resistance in unipolar depression, treatment-resistant bipolar depression is poorly defined and largely unstudied. Literature review finds neither a definition for treatment-refractory bipolar depression nor any controlled studies reporting the outcome of treatments for samples of bipolar patients described as treatment refractory. Consensus definitions for recovery, relapse, and recurrence have advanced research on treatment-refractory unipolar depression, but there is no consensus on how to apply these concepts to bipolar illness. Confidence in the assessment of treatment outcome for bipolar depressed patients is limited by the irregular episodic course of the illness, potential for affective switch, and problems inherent to the direct assessment of mood elevation. Defining treatment response on the basis of change in depression rating scales scores can result in mislabeling a clear worsening in a patient's clinical condition as recovery. During the course of antidepressant therapy, some depressed bipolar patients enjoy an apparent remission of depressive symptoms, but they are experiencing manic symptoms rather than euthymia.

The resultant lack of clarity is a major obstacle that must be overcome before a clear definition of what constitutes treatment-refractory bipolar depression can be offered and meaningful research can address treatment-resistant bipolar illness.

While acknowledging these problems, this article offers a conceptual overview of treatment-refractory bipolar depression and attempts to address the clinical management of refractory bipolar depression.