Vol. 8, Issue 1, Part A (2026)

Depression is a common and debilitating comorbidity in patients with Multiple Sclerosis (MS), often resistant to conventional treatments such as selective serotonin reuptake inhibitors (SSRIs) and transcranial magnetic stimulation (TMS). This case report describes a 39-year-old male with relapsing MS and treatment-resistant depression, who demonstrated minimal response to multiple antidepressants and TMS therapy. Initiation of esketamine (Spravato) therapy resulted in a significant and sustained reduction in depressive symptoms, as measured by PHQ-9 scores, with a 77.8% improvement from baseline. Symptom improvement correlated with enhanced social engagement, cognitive function, and daily motivation, despite occasional transient increases in PHQ-9 scores due to situational stressors. This case highlights the potential efficacy of Spravato as an alternative treatment for depression in patients with neurological disorders, particularly when standard therapies fail. Further controlled studies are warranted to confirm these findings and explore underlying neurobiological mechanisms.