Is treatment-resistant depression a unique subtype of depression?

Treatment-resistant depression (TRD) continues to represent a major challenge for treating clinicians. This report reviews the relevant literature to evaluate whether TRD can be considered a specific subtype of depression based on 1) clinical characteristics and course (behavioral phenotype), 2) neurobiological profile, and 3) context and environment in which TRD develops. Although patients with TRD share a number of clinical, neurobiological, and context and environment characteristics, the lack of available data and the clinical heterogeneity of this condition do not currently permit the classification of TRD as a unique subtype of depression; however, this topic is worthy of further evaluation and research. Performing genetics and neuroimaging studies on patients enrolled in large, prospective and controlled studies may provide enough data for classifying TRD (or at least a part of what is currently described as TRD) as a specific subtype of depression. This in turn may facilitate the identification of more effective treatment strategies.