Treatment-resistant depression reconsidered

Abstract

The term treatment-resistant depression (TRD) has been the focus of hundreds of studies and clinical trials, though it is not a diagnosable mental health condition according to current clinical standards. The term implies depression that is particularly difficult to treat. However, as we illustrate here, the use of the TRD construct creates significant concerns regarding patient welfare and optimal distribution of resources. First, TRD is frequently defined as depression that failed to respond to antidepressant medication. Therefore, patients may be labeled with TRD after having tried just one medication, without consideration of effective non-pharmacological treatments such as psychotherapy or holistic interventions to improve sleep, nutrition, and exercise. Second, TRD implicitly contextualizes depression as a problem within an individual's brain, ignoring larger systemic, developmental, and sociological factors known to be depressogenic. Important structural determinants of health such as social isolation, environmental stressors, systemic oppression, unmet basic needs for shelter, food, and safety are excluded. Third, TRD does a disservice to patients when it rapidly escalates treatment decisions to increasingly risky and experimental options. And finally, the existing concept of TRD is used to justify enormous financial investment – on the order of billions of dollars - in research aimed at identifying precise biological treatment targets. The quest for biomedical treatments struggles to provide the anticipated return on investment in the form of decreased depression burden despite over 50 years of costly effort. Drawing from historical perspectives, we highlight these issues and propose recommendations to address them.