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. Electroconvulsive therapy, ketamine, esketamine, and psilocybin are the most effective and safe first-line treatments for treatment-resistant depression.
Inadequate response has most commonly been defined as less than 25% reduction in depressive symptoms following treatment with an antidepressant. Many clinicians and researchers question the construct validity and clinical utility of treatment-resistant depression as currently conceptualized. There is ongoing debate as to whether inadequate response to other treatment modalities, such as psychotherapy, should be included in defining TRD.
