Investigating the Effects of Intranasal Esketamine on Suicidal Ideation in Patients with Treatment-Resistant Depression

Treatment-resistant depression (TRD) remains a significant challenge, with many patients failing conventional treatments. While intranasal esketamine has demonstrated efficacy for depression, its specific effects on suicidal ideation (SI)—a critical symptom of depression—are underexplored. Unlike most studies that adhere to the 84mg dosing paradigm administered twice weekly, this study explores the novel use of varying esketamine doses, including 54mg, 84mg, and 112mg. This study aims to evaluate the impact of varying esketamine doses (54mg, 84mg, and 112mg) on SI in a real-world outpatient population (n=24). This study analyzed data from patients in Southwest Michigan with major depressive disorder (MDD) and psychiatric comorbidities who received intranasal esketamine treatments between July 2022 and July 2024. The primary outcome was change in SI, measured by question 9 on the Patient Health Questionnaire-9 (PHQ-9). Preliminary findings suggest that an increase in the esketamine dose to 112mg was associated with lower SI scores, especially when comparing 84mg to 112mg (p=0.025).This indicates that patients may benefit from a higher dose, especially those who have had inadequate responses to the standard 84mg dosing paradigm. Based on these results, a trial of 112mg esketamine could be considered for patients with insufficient improvement on the typical dosing regimen. This study provides initial evidence that intranasal esketamine may reduce SI in TRD patients. Further research is necessary to refine dosing and investigate esketamine’s broader effects on mental health outcomes, especially in high-risk populations.