Overview of treatment-resistant depression.

Treatment-resistant depression (TRD) describes patients with major depressive disorder who do not respond adequately to antidepressant drugs. Compared to those without TRD, affected individuals have lower health-related quality of life, more functional impairment and productivity loss, and higher healthcare costs, imposing a massive burden on individuals, families, and society. A lack of consensus on the definition of TRD limits comparison of treatment efficacy across trials and results in scarce treatment guidelines specifically for TRD. This chapter reviews common issues including definitions of an adequate antidepressant trial and TRD, prevalence and clinical outcomes, staging models, variations in definitions, and up-to-date treatment options such as pharmacological strategies, psychotherapeutic interventions, neurostimulation, glutamatergic compounds, and experimental agents.

Study at a glance

Abstract

Patients with major depressive disorder (MDD) often exhibit an inadequate treatment response or failure to achieve remission following treatment with antidepressant drugs. Treatment-resistant depression (TRD) is proposed to identify this clinical scenario. Compared to those without TRD, patients with TRD have significantly lower health-related quality of life in mental and physical dimensions, more functional impairment and productivity loss, and higher healthcare costs. TRD imposes a massive burden on the individual, family, and society. However, a lack of consensus on the TRD definition limits the comparison and interpretation of TRD treatment efficacy across trials. Furthermore, because of the various TRD definitions, there is scarce treatment guideline specifically for TRD, in contrast to the rich treatment guidelines for MDD. In this chapter, common issues related to TRD, such as proper definitions of an adequate antidepressant trial and TRD, were carefully reviewed. Prevalence of and clinical outcomes related to TRD were summarized. We also summarized the staging models ever proposed for the diagnosis of TRD. Furthermore, we highlighted variations in the definition regarding the lack of or an inadequate response in treatment guidelines for depression. Up-to-date treatment options for TRD, including pharmacological strategies, psychotherapeutic interventions, neurostimulation techniques, glutamatergic compounds, and even experimental agents were reviewed.