Definition
A subtype of major depressive disorder defined by inadequate response to at least two adequate trials of antidepressant medications from different classes.
In Depth
Treatment-resistant depression (TRD) affects roughly 30% of patients with major depressive disorder. Definitions vary, but the most common requires failure of two adequate-dose, adequate-duration antidepressant trials from different mechanism-of-action classes.
Treatment options include augmentation strategies (lithium, atypical antipsychotics), ketamine/esketamine, transcranial magnetic stimulation (TMS), and electroconvulsive therapy (ECT).
Related Terms
Esketamine
The (S)-enantiomer of ketamine, FDA-approved as the nasal spray Spravato for treatment-resistant depression and depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior.
Ketamine-Assisted Therapy
A clinical protocol in which sub-anesthetic doses of ketamine are administered (IV, IM, oral, or intranasal) under medical supervision to treat depression, PTSD, anxiety, or chronic pain — typically combined with structured psychotherapy.
TMS
Transcranial Magnetic Stimulation — an FDA-cleared, non-invasive brain stimulation therapy delivered through magnetic pulses applied to the scalp. Used for major depression, OCD, and smoking cessation.
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