Definition of treatment-resistant depression

To date, there is no established consensus as to the definition of treatment resistant depression (TRD). Nevertheless, a useful pragmatic approach is to define TRD broadly, as the failure of an episode of major depression to respond fully to a treatment known to be effective in major depression. This implies that TRD exists along a continuum rather than as an all-or-none phenomenon with varying degrees of treatment resistance. It ranges from a minimal or zero response to adequate antidepressant treatment (what has been termed treatment-refractory depression by Fawcett, 1994), to the more general problem of partial but incomplete response, where clinically there is some improvement in the patients condition but insufficient to achieve remission. In the literature remission in clinical studies is usually defined as an endpoint score on the Hamilton Rating Scale for Depression (HDRS) of ≤ 7, and possibly in addition, a physician rated Clinical Global Impression-Improvement (CGI-I) score= 1 (i.e. very much improved). When this more rigorous benchmark is applied, only about 30% of patients in clinical trials will actually achieve remission of symptoms at the end of a 6- or 8-week trial of an antidepressant, so the problem of TRD, to one extent or another, is a very substantial one.

Categories of TRD

Given the fact that the population of TRD patients is a heterogeneous one, some stratification is important in both conceptualization and development of treatment approaches.