Treatment-resistant depression is a term frequently used when depressive symptoms persist despite appropriate trials of antidepressant medication and psychological therapy. While the definition typically refers to inadequate response following at least two antidepressant trials of adequate dose and duration, the clinical reality is often more nuanced.

In practice, persistent depressive symptoms do not always reflect biological non-response alone. They may signal incomplete diagnostic clarification, untreated comorbid conditions, psychosocial stressors, medication tolerability issues, or underlying bipolar spectrum features. In some cases, longstanding anxiety, trauma-related presentations or undiagnosed ADHD may contribute to ongoing functional impairment that is attributed solely to depression.

For this reason, a structured reassessment is often clinically valuable before escalating treatment. This may include review of previous medication trials, examination of adherence and duration, reassessment of diagnostic formulation, and careful consideration of comorbid presentations. The objective is not simply to add further treatment, but to ensure that the underlying conceptualisation of the illness remains accurate.

Where depressive illness persists despite adequate treatment and diagnostic clarity, augmentation strategies or alternative biological therapies may be considered within a carefully monitored framework. Such decisions require individualised assessment, medical suitability and ongoing review.

Treatment-resistant depression is therefore best approached not as a fixed category, but as an invitation to reassess, refine and clarify. Careful formulation remains central to effective psychiatric practice.