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Is treatment-resistant depression a useful concept?
  1. Gin S Malhi1,2,3,
  2. Yulisha Byrow1,2
  1. 1Department of Psychiatry, CADE Clinic, Royal North Shore Hospital, Sydney, New South Wales, Australia;
  2. 2Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia;
  3. 3Kolling Institute, Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia
  1. Correspondence to Professor Gin S Malhi, Department Head and Chair of Psychiatry, Advanced Research High-field Imaging Facility, Kolling Institute, Clinical and Research Director CADE Clinic, Level 3, Main Hospital Building, Royal North Shore Hospital, St. Leonard's, Sydney, NSW 2065, Australia; Gin.malhi{at}


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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