Efficacy of Intranasal Esketamine in Treatment-Resistant Depression: A Six-Month Real-World Follow-Up Study of Depressive Symptoms, Hopelessness, and Suicide Risk.
Maurizio Pompili, Maria Anna Trocchia, Ludovica Longhini, Eva Dispenza, Cristina Di Legge, Salvatore Sarubbi, Denise Erbuto, Isabella Berardelli
Human psychopharmacology July 1, 2025 DOI: 10.1002/hup.70008
Summary
Intranasal esketamine significantly reduced depressive symptoms and hopelessness in patients with severe, persistent depression. This investigation explored how intranasal esketamine affects those battling treatment-resistant depression. Researchers followed 21 patients receiving esketamine, tracking their depressive symptoms, feelings of hopelessness, and suicide risk over six months. Results showed a clear reduction in depressive symptoms and hopelessness. Crucially, there was a significant decrease in suicidal ideation, highlighting esketamine's potential for suicide prevention. This suggests a positive impact on mental well-being and reducing suicide risk in those with hard-to-treat depression.
Abstract
Treatment-resistant depression is one of the most significant clinical challenges in psychiatric practice. The primary aim of the present study was to assess the efficacy and tolerability of intranasal esketamine on depressive symptoms in a real-world outpatient setting. A secondary objective was to explore the potential benefits of intranasal esketamine on hopelessness and suicide risk (suicidal ideation and suicide attempts). Twenty-one patients diagnosed with treatment-resistant depression were treated with intranasal esketamine. Depressive symptoms (MADRS and BDI), suicide risk (C-SSRS), and hopelessness (BHS) were assessed. We conducted a mixed model for repeated measures analysis to evaluate changes from baseline (T0), 3-month follow-up (T1), and 6-month follow-up (T2). Results indicated that depressive symptoms decreased over time. Specifically, both clinician and self-report measures show lower levels of depressive symptoms at 3-month and 6-month follow-up. We also found a significant decrease in the presence of suicidal ideation between T0 and T2. Finally, patients also reported a reduction in hopelessness levels over time. Our findings indicate an overall response regarding depressive symptoms, hopelessness, and suicidal ideation after esketamine in treatment-resistant depression at 3-month and 6-month follow-up assessments.