Treatment-Resistant Depression

The standard model of prescribing successive antidepressants without investigating inflammatory root causes misses the mechanism driving non-response. TRD affects 20–30% of all MDD patients, representing approximately 2.8 million people in the US. Patients with TRD consistently show elevated inflammatory biomarkers. MDD comorbidity overlaps with cardiovascular disease, diabetes, autoimmune disease, and dementia, suggesting shared upstream inflammatory root causes. MDD carries approximately a 15% lifetime suicide risk, most often occurring during an active depressive episode. Treatment-resistant depression is defined as failure to respond to at least two adequate antidepressant trials of SSRI or SNRI medications.