Refractory Depression is a term used in clinical psychiatry to describe cases of major depressive disorder that do not respond to typical modes of treatment, such as psychotherapy and common antidepressants such as SSRIs.

Treatment of refractory depression has traditionally most commonly involved electroconvulsive therapy and use of non-standard medications, but new technologies such as transcranial magnetic stimulation are being studied as a safer alternative. Treatment of refractory depression may also involve more invasive interventions, such as vagus nerve stimulation.