Bipolar spectrum disorders in apparent treatment-resistant depression: diagnostic pitfalls and implications for contemporary psychiatric practice

SUMMARY Patients referred with apparent treatment-resistant depression (TRD) are a diagnostically heterogeneous group. A clinically important minority have unrecognised bipolar spectrum disorders (BSD), most commonly bipolar II disorder, cyclothymic disorder or depressive episodes with mixed features. Misclassification may result from brief, subtle or retrospectively underreported hypomania, the categorical nature of DSM/ICD diagnostic thresholds and under-recognition of mixed depressive states. This article gives a practical framework for identifying patients in whom antidepressant non-response, mood instability, antidepressant-induced agitation/switching, recurrent or early-onset depression, and mixed features should prompt consideration of underlying BSD through differential diagnosis, recognition of clinical red flags and structured diagnostic reassessment. Rather than redefining TRD or suggesting that most TRD cases are bipolar, the article aims to improve diagnostic accuracy by highlighting circumstances in which bipolar spectrum illness should be considered before further treatment escalation. It also summarises implications for pharmacological management and briefly considers neuromodulation as one option when bipolarity is suspected but not yet recognised.