Numerous approaches have been used to define and stage treatment-resistant depression (TRD) as well as to find predictors of treatment outcome. Nevertheless, TRD remains a complex disorder, with high morbidity and mortality. This paper briefly reviews current guidelines for managing TRD, summarising the best pharmacological strategies and ‘next steps’ of psychological and physical treatments. When depressed patients fail to remit after two or more conventional antidepressant treatments, combined approaches, targeting multiple molecular, psychological and physical mechanisms, seem to be the most effective strategy.
Keywords: treatment-resistant depression, antidepressants, combined approaches, somatic therapies, predictors