Treatment-resistant depression (TRD) is a type of major depressive disorder characterized by the persistence of depressive symptoms despite adequate trials of at least two different antidepressant medications, such as a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI). It may require alternative approaches, like talk therapy, or more intensive treatment approaches, like ketamine or brain stimulation, to achieve symptom relief.