Treatment-resistant depression

Treatment-resistant depression, or TRD, is major depressive disorder that does not respond adequately to at least two different antidepressant medications, each given at an adequate dose for an adequate duration. Inadequate response is typically defined as less than a 25 percent reduction in depressive symptoms following an antidepressant trial. Under this definition, nearly 30 percent of people with major depressive disorder are considered treatment resistant, though clinicians and researchers continue to debate whether current definitions properly capture the condition's complexity. Apparent treatment failure can also stem from undiagnosed co-occurring conditions, poor medication adherence, ongoing psychosocial stress, or diagnostic error rather than true resistance. Despite the name, several evidence-based treatments exist beyond standard antidepressants, including electroconvulsive therapy, ketamine and esketamine, and neuromodulation techniques such as repetitive transcranial magnetic stimulation, along with various adjunctive medications. It falls under psychiatry, and its symptoms include depressed mood, anhedonia and low energy, with complications that can include self-harm and suicide.