Paradigm shift in study of treatment-resistant psychiatric disorder

Psychiatric patients with many episodes that do not respond satisfactorily to numerous sequential treatment regimens were included in the treatment resistance studies. Most studies have, however, used a post hoc experimental design that failed to determine the association between biomarkers and the initial risk of treatment-resistant psychiatric disorder (TRP). Such post hoc experimental design can be regarded only as a consequence of having treatment resistance, rather than being a causal risk factor for it. Although informative, data derived from such studies often do not allow for a distinction to be made between cause and effect. To deal with this problem, it is most ideal to enroll untreated patients (those who were diagnosed but have not yet undergone treatment) as study subjects. In this chapter, the authors will review methodological considerations to uncover initial biological risk factors for TRP and propose a better study design for future research by discussing the shortcomings of the traditional study design.