Treatment-resistant depression

Treatment-resistant depression (TRD) is often defined as major depressive disorder in which an affected person does not respond adequately to at least two different antidepressant medications at an adequate dose and for an adequate duration.^[1] Inadequate response has most commonly been defined as less than 25% reduction in depressive symptoms following treatment with an antidepressant.^[2] Many clinicians and researchers question the construct validity and clinical utility of treatment-resistant depression as currently conceptualized.^[3][4] There is ongoing debate as to whether inadequate response to other treatment modalities, such as psychotherapy, should be included in defining TRD.^[5]

Treatment resistance is becoming more prominent with nearly 30% of individuals with major depressive disorder being termed treatment-resistant as defined above.^[6] There are many factors that may contribute to inadequate treatment, such as: a history of repeated or severe adverse childhood experiences, early discontinuation of treatment, failure to consider psychotherapy and other psychosocial interventions, patient noncompliance, misdiagnosis, cognitive impairment, low income and other social determinants, and concurrent medical conditions, including comorbid psychiatric disorders.^[2] Cases of treatment-resistant depression may also be referred to by which medications people are resistant to (e.g., SSRI-resistant).^[7] They may also be staged based on how many treatments they have tried.^[8] Despite being called treatment-resistant, there are many treatment options available which are described in the treatment section below.