Use of Intranasal Esketamine in suicidal ideation in patients with treatment-resistant depression
DOI:
https://doi.org/10.55892/jrg.v9i20.3194Keywords:
Esketamine, Treatment-Resistant Depression, Suicidal Ideation, Antidepressants, SuicideAbstract
Treatment-resistant depression (TRD) represents a significant clinical challenge, particularly when associated with suicidal ideation, a condition that requires rapid therapeutic intervention. In this context, intranasal esketamine has emerged as a promising alternative due to its rapid antidepressant effects. The present study aimed to critically analyze the available evidence regarding the use of intranasal esketamine in suicidal ideation among patients with treatment-resistant depression. This is a narrative literature review with an analytical and critical approach, based on searches conducted in PubMed/MEDLINE, ScienceDirect, and SciELO, considering publications from the last ten years. A total of 16 studies were included, comprising randomized clinical trials, systematic reviews, meta-analyses, and observational studies. The findings indicate that esketamine produces a rapid and consistent antidepressant effect, with significant reductions in depressive symptoms within hours of administration. Regarding suicidal ideation, short-term reductions were observed, particularly in acute crisis settings; however, these effects were less consistent and not sustained over time. The critical analysis suggests that improvements in suicidal ideation may be partially related to overall reductions in depressive symptoms, and current evidence does not support a specific and independent antisuicidal effect. In conclusion, although intranasal esketamine represents a relevant advancement in the management of TRD, important gaps remain regarding its sustained efficacy in reducing suicidal ideation, highlighting the need for further studies with more robust methodological designs.
Downloads
References
AMMENDOLIA, I. et al. Safety profile and suicidality associated with the use of esketamine in the treatment of major depressive disorder in European countries: an EudraVigilance database analysis. Pharmaceuticals, v. 18, n. 5, 702, 2025. DOI 10.3390/ph18050702.
ALARIO, A. A.; NICIU, M. J. (Es)Ketamine for suicidal ideation and behavior: clinical efficacy. Chronic Stress, v. 6, 2022. DOI 10.1177/24705470221128017.
BOUDIEU, L. et al. The efficacy and safety of intranasal formulations of ketamine and esketamine for the treatment of major depressive disorder: a systematic review. Pharmaceutics, v. 15, n. 12, 2773, 2023. DOI 10.3390/pharmaceutics15122773.
CANUSO, C. M. et al. Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: results of a double-blind, randomized, placebo-controlled study. American Journal of Psychiatry, v. 175, n. 7, p. 620-630, 2018. DOI 10.1176/appi.ajp.2018.17060720.
IONESCU, D. F. et al. Esketamine nasal spray for rapid reduction of depressive symptoms in patients with major depressive disorder who have active suicidal ideation with intent: results of a phase 3, double-blind, randomized study (ASPIRE II). International Journal of Neuropsychopharmacology, v. 24, n. 1, p. 22-31, 2021. DOI 10.1093/ijnp/pyaa068.
JOLLANT, F. et al. Ketamine and esketamine in suicidal thoughts and behaviors: a systematic review. Therapeutic Advances in Psychopharmacology, v. 13, 2023. DOI 10.1177/20451253231151327.
JIVRAJ, A. P. et al. Navigating treatment-resistant major depressive disorder with suicidal ideation: exploring the efficacy of Spravato (Esketamine) in an 86-year-old male. Cureus, v. 16, n. 12, e76090, 2024. DOI 10.7759/cureus.76090.
KAVAKBASI, E. et al. Intranasal esketamine significantly alleviates depression severity and suicidal ideations in electroconvulsive therapy (ECT) non-responders. European Archives of Psychiatry and Clinical Neuroscience, v. 275, p. 2379-2387, 2025. DOI 10.1007/s00406-025-02041-9.
KUMARI, S. et al. Exploring esketamine's therapeutic outcomes as an FDA-designated breakthrough for treatment-resistant depression and major depressive disorder with suicidal intent: a narrative review. Cureus, v. 16, n. 2, e53987, 2024. DOI 10.7759/cureus.53987.
LEONARDI, M. et al. Effectiveness of intranasal esketamine on suicidal ideation and depressive symptoms in patients with treatment-resistant depression: a longitudinal study. Journal of Clinical Medicine, v. 15, n. 1, 250, 2026. DOI 10.3390/jcm15010250.
LIU, H. et al. The efficacy and safety of esketamine in the treatment of major depressive disorder with suicidal ideation: study protocol for a randomized controlled trial. BMC Psychiatry, v. 22, 744, 2022. DOI 10.1186/s12888-022-04388-y.
POMPILI, M. Intranasal esketamine and current suicidal ideation with intent in major depression disorder: beat the clock, save a life, start a strategy. Frontiers in Psychiatry, v. 11, 325, 2020. DOI 10.3389/fpsyt.2020.00325.
POMPILI, M. et al. Efficacy of intranasal esketamine in treatment-resistant depression: a six-month real-world follow-up study of depressive symptoms, hopelessness, and suicide risk. Human Psychopharmacology: Clinical and Experimental, v. 40, e70008, 2025. DOI 10.1002/hup.70008.
PATARROYO-RODRIGUEZ, L. et al. Ketamine reduces suicidality-associated emergency department utilization in patients with treatment-resistant depression: a 6-month mirror-image study. Journal of Clinical Psychiatry, v. 86, n. 4, 25m15941, 2025. DOI 10.4088/JCP.25m15941.
WANG, S. M. et al. Rapid onset of intranasal esketamine in patients with treatment resistant depression and major depression with suicide ideation: a meta-analysis. Clinical Psychopharmacology and Neuroscience, v. 19, n. 2, p. 341-354, 2021. DOI 10.9758/cpn.2021.19.2.341.
ZHDANAVA, M. et al. Esketamine nasal spray for major depressive disorder with acute suicidal ideation or behavior: description of treatment access, utilization, and claims-based outcomes in the United States. Journal of Medical Economics, v. 26, n. 1, p. 691-700, 2023. DOI 10.1080/13696998.2023.2208993.
