The Deceptive Manifestations of Treatment Resistance in Depression: A New Look at the Problem

In the past decade, the number of papers dealing with treatment resistance in depression has increased to a considerable degree. It has recently been discussed whether current definitions of treatment resistance are appropriate: issues of misdiagnosis, diagnostic and biological heterogeneity, and suboptimal therapeutic strategies have been raised [1–3]. However, current conceptualizations of treatment resistance focus on the characteristics of the patient (whether neurobiological assets, or attitudes, or psychiatric comorbidity) for the insufficient effectiveness of antidepressant drugs and omit any reference to the potential iatrogenic effects of treatment [4], as if, in the field of infectious disease, treatment resistance were conceptualized independently of the previous use of antibiotics. We will try to outline some historical developments of the concept of treatment resistance in depression and how a different assessment strategy is required to address current clinical challenges.