Is treatment-resistant depression a useful concept?

Abstract

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.

Figure 1

Important aspects of antidepressant treatment are the timing and pattern of response. Debate concerning the duration of antidepressant treatment reflects uncertainty as to when response typically occurs, if it emerges at all. The speed of response varies considerably, as does its extent—with the majority of individuals experiencing a delay and/or only a partial response. It is important to note that rapid responders may be a different group to slow responders—forming perhaps another type (degree) of treatment-resistant depression (TRD). Similarly those that respond only partially may be regarded as another subtype of TRD. In the figure response (y axis) is charted according to time (x axis). The various lines indicate potential response trajectories. The blue lines indicate complete response, the green lines indicate partial response and the red line indicates no response. The dashed lines denote a delay in response. The graded red shading indicates degree of treatment resistance, which increases as the time to a response increases and the extent of the response decreases.