Intranasal Esketamine in Patients with Treatment-resistant Depression Who Have Previously Failed Transcranial Magnetic Stimulation: A Case Series.

Treatment-resistant depression (TRD) is major depression that has not responded to at least two trials of antidepressants. The STAR-D study highlighted the necessity of multiple treatment steps to achieve remission, with each step decreasing the likelihood of success and increasing relapse risk, underscoring the complexity of TRD treatment and the need for personalized approaches. Transcranial magnetic stimulation (TMS) is a noninvasive technique using magnetic fields to stimulate brain nerve cells, targeting the dorsolateral prefrontal cortex, that is effective in many patients with depression. However, for patients with TRD who fail TMS, no standard of care exists. Intranasal esketamine, a noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is approved for adults with TRD or major depressive disorder with suicidal thoughts. We present a case series of five patients with TRD who failed TMS and subsequently responded to intranasal esketamine. Response, defined as a 50-percent symptom reduction, was monitored using Patient Health Questionnaire (PHQ-9), Beck Depression Inventory (BDI), and Generalized Anxiety Disorder-7 (GAD-7) scores. After 16 treatment sessions, all patients achieved a treatment response per PHQ-9 and BDI scores; 80 percent achieved complete remission per PHQ-9, and 60 percent per BDI. Additionally, 80 percent of patients showed a treatment response on GAD-7 scores. This case series supports further investigation into esketamine for patients with TRD who are unresponsive to TMS.