Abstract
Treatment-resistant depression (TRD) remains a significant clinical challenge, often accompanied by polypharmacy and comorbid anxiety or trauma-related disorders. This report describes a 37-year-old male with longstanding major depressive disorder (MDD), post-traumatic stress disorder (PTSD), and social anxiety disorder who demonstrated limited response to traditional pharmacologic strategies, including escitalopram, quetiapine, trazodone, and gabapentin. After initiating low-dose sublingual ketamine troches, the patient experienced clinically meaningful improvements in depression and anxiety scores. These improvements were accompanied by successful tapering and discontinuation of four psychotropic medications. No adverse effects were reported. This case highlights the potential utility of sublingual ketamine in reducing symptom burden and supporting deprescribing efforts in complex TRD presentations.