The term treatment-resistant depression (TRD) is widely used in the context of managing mood disorders, but defining it, both conceptually and in practice, has proven difficult. Most definitions have focused on pharmacotherapy but even these have struggled to capture the complexity of varying response and duration of treatment. Both clinically and for research studies a meaningful definition of TRD is necessary because it may lead to the development of ‘therapy-defined depressive subtypes’ and the discovery of novel antidepressants. This brief perspective critically reviews the concept of treatment resistance and how it can be more clearly defined so as to achieve a better understanding of depression and facilitate clinical treatment trials.
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