ESKETAMINE AND DEEP BRAIN STIMULATION IN TREATMENT-RESISTANT DEPRESSION: A LITERATURE REVIEW
DOI:
https://doi.org/10.31435/ijitss.1(49).2026.5003Keywords:
Depression, Esketamine, Ketamine, Deep Brain StimulationAbstract
Background: Depression is a significant mental health condition affecting numerous individuals worldwide, leading to disability within society and posing a heightened risk of suicide, thereby diminishing overall quality of life. Depression, often a contributing factor in suicides, is associated with various prevalent medical conditions such as obesity, diabetes, stroke, Parkinson's disease, and multiple sclerosis. Treatment-resistant depression (TRD) affects approximately 30% of patients with major depressive disorder.
Aim of the study: This study aims to assess the efficacy of modern depression treatments such as intranasal esketamine administration and deep brain stimulation.
Material and methods: A review of literature was conducted using several scientific databases, including PubMed, Scopus, Web of Science, and Google Scholar. Only articles in English were included for further analysis. The keywords used were: “depression”, “esketamine”, “ketamine”, and “deep brain stimulation”. Ultimately, 30 articles were selected for analysis.
Results: Intranasal esketamine has shown promising results, including improved well-being and alleviation of symptoms, although caution is advised in patients with hypertension. While deep brain stimulation is traditionally used for movement disorders like Parkinson's disease, recent findings suggest its potential as a viable treatment for severe depression. Long-term studies indicate that both approaches effectively facilitate remission of depression.
Conclusions: Depression poses a significant threat to individuals' health and well-being, necessitating a comprehensive treatment approach. Tailored strategies encompassing pharmaceutical interventions, surgical procedures, and psychotherapy can collectively contribute to substantial improvements in daily functioning and reduce the risk of suicidal behaviors.
References
Pearce, M., Garcia, L., Abbas, A., Strain, T., Schuch, F. B., Golubic, R., et al. (2022). Association between physical activity and risk of depression. JAMA Psychiatry, 79(6), 550. https://doi.org/10.1001/jamapsychiatry.2022.0609
Dudek, K. A., Dion-Albert, L., Kaufmann, F. N., Tuck, E., Lebel, M., & Menard, C. (2021). Neurobiology of resilience in depression: Immune and vascular insights from human and animal studies. European Journal of Neuroscience, 53(1), 183–221. https://doi.org/10.1111/ejn.14547
Akil, H., Gordon, J., Hen, R., Javitch, J., Mayberg, H., McEwen, B., et al. (2018). Treatment resistant depression: A multi-scale, systems biology approach. Neuroscience & Biobehavioral Reviews, 84, 272–288. https://doi.org/10.1016/j.neubiorev.2017.08.019
Kverno, K. S., & Mangano, E. (2021). Treatment-resistant depression: Approaches to treatment. Journal of Psychosocial Nursing and Mental Health Services, 59(9), 7–11. https://doi.org/10.3928/02793695-20210816-01
Amos, T. B., Tandon, N., Lefebvre, P., Pilon, D., Kamstra, R. L., Pivneva, I., et al. (2018). Direct and indirect cost burden and change of employment status in treatment-resistant depression. Journal of Clinical Psychiatry, 79(2), 24–32. https://doi.org/10.4088/JCP.17m11725
Daly, E. J., Singh, J. B., Fedgchin, M., Cooper, K., Lim, P., Shelton, R. C., et al. (2018). Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression. JAMA Psychiatry, 75(2), 139. https://doi.org/10.1001/jamapsychiatry.2017.3739
Daly, E. J., Trivedi, M. H., Janik, A., Li, H., Zhang, Y., Li, X., et al. (2019). Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in treatment-resistant depression. JAMA Psychiatry, 76(9), 893. https://doi.org/10.1001/jamapsychiatry.2019.1189
Fedgchin, M., Trivedi, M., Daly, E. J., Melkote, R., Lane, R., Lim, P., et al. (2019). Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression. International Journal of Neuropsychopharmacology, 22(10), 616–630. https://doi.org/10.1093/ijnp/pyz039
Popova, V., Daly, E. J., Trivedi, M., Cooper, K., Lane, R., Lim, P., et al. (2019). Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression. American Journal of Psychiatry, 176(6), 428–438. https://doi.org/10.1176/appi.ajp.2019.19020172
Wajs, E., Aluisio, L., Holder, R., Daly, E. J., Lane, R., Lim, P., et al. (2020). Esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression. Journal of Clinical Psychiatry, 81(3). https://doi.org/10.4088/JCP.19m12891
Katz, E. G., Hough, D., Doherty, T., Lane, R., Singh, J., & Levitan, B. (2021). Benefit–risk assessment of esketamine nasal spray vs. placebo in treatment-resistant depression. Clinical Pharmacology & Therapeutics, 109(2), 536–546. https://doi.org/10.1002/cpt.2024
Ionescu, D. F., Fu, D.-J., Qiu, X., Lane, R., Lim, P., Kasper, S., et al. (2021). Esketamine nasal spray for rapid reduction of depressive symptoms in patients with major depressive disorder and active suicidal ideation with intent. International Journal of Neuropsychopharmacology, 24(1), 22–31. https://doi.org/10.1093/ijnp/pyaa068
Kennard, B. D., Silva, S. G., Tonev, S., Rohde, P., Hughes, J. L., Vitiello, B., et al. (2009). Remission and recovery in TADS: Acute and long-term outcomes. Journal of the American Academy of Child & Adolescent Psychiatry, 48(2), 186–195. https://doi.org/10.1097/CHI.0b013e31819176f9
Emslie, G. J., Mayes, T., Porta, G., Vitiello, B., Clarke, G., Wagner, K. D., et al. (2010). TORDIA: Week 24 outcomes. American Journal of Psychiatry, 167(7), 782–791. https://doi.org/10.1176/appi.ajp.2010.09040552
Vitiello, B., Emslie, G., Clarke, G., Wagner, K. D., Asarnow, J. R., Keller, M. B., et al. (2011). Long-term outcome of adolescent depression initially resistant to SSRI treatment. Journal of Clinical Psychiatry, 72(3), 388–396. https://doi.org/10.4088/JCP.09m05885blu
Dwyer, J. B., Landeros-Weisenberger, A., Johnson, J. A., Londono Tobon, A., Flores, J. M., Nasir, M., et al. (2021). Efficacy of IV ketamine in adolescent treatment-resistant depression. American Journal of Psychiatry, 178(4), 352–362. https://doi.org/10.1176/appi.ajp.2020.20010018
Vitek, J. L., Jain, R., Chen, L., Tröster, A. I., Schrock, L. E., House, P. A., et al. (2020). Subthalamic nucleus DBS with a constant current-controlled device in Parkinson’s disease (INTREPID). Lancet Neurology, 19(6), 491–501. https://doi.org/10.1016/S1474-4422(20)30108-3
Lozano, A. M., Giacobbe, P., Hamani, C., Rizvi, S. J., Kennedy, S. H., Kolivakis, T. T., et al. (2012). Subcallosal cingulate DBS for TRD: Multicenter pilot study. Journal of Neurosurgery, 116(2), 315–322. https://doi.org/10.3171/2011.10.JNS102122
Riva-Posse, P., Choi, K. S., Holtzheimer, P. E., Crowell, A. L., Garlow, S. J., Rajendra, J. K., et al. (2018). A connectomic approach for SCC DBS surgery in TRD. Molecular Psychiatry, 23(4), 843–849. https://doi.org/10.1038/mp.2017.59
Holtzheimer, P. E., Husain, M. M., Lisanby, S. H., Taylor, S. F., Whitworth, L. A., McClintock, S., et al. (2017). SCC DBS for TRD: Multisite sham-controlled trial. Lancet Psychiatry, 4(11), 839–849. https://doi.org/10.1016/S2215-0366(17)30371-1
Dougherty, D. D., Rezai, A. R., Carpenter, L. L., Howland, R. H., Bhati, M. T., O’Reardon, J. P., et al. (2015). DBS of VC/VS for chronic TRD: Randomized sham-controlled trial. Biological Psychiatry, 78(4), 240–248. https://doi.org/10.1016/j.biopsych.2014.11.023
Sheth, S. A., Bijanki, K. R., Metzger, B., Allawala, A., Pirtle, V., Adkinson, J. A., et al. (2022). DBS for depression informed by intracranial recordings. Biological Psychiatry, 92(3), 246–251. https://doi.org/10.1016/j.biopsych.2021.11.007
van der Wal, J. M., Bergfeld, I. O., Lok, A., Mantione, M., Figee, M., Notten, P., et al. (2020). Long-term DBS of vALIC for TRD. Journal of Neurology, Neurosurgery & Psychiatry, 91(2), 189–195. https://doi.org/10.1136/jnnp-2019-321758
Bergfeld, I. O., Mantione, M., Hoogendoorn, M. L. C., Ruhe, H. G., Notten, P., van Laarhoven, J., et al. (2016). DBS of vALIC for TRD. JAMA Psychiatry, 73(5), 456. https://doi.org/10.1001/jamapsychiatry.2016.0152
Ramasubbu, R., Clark, D. L., Golding, S., Dobson, K. S., Mackie, A., Haffenden, A., et al. (2020). Short vs long pulse width SCC stimulation for TRD: Randomized crossover trial. Lancet Psychiatry, 7(1), 29–40. https://doi.org/10.1016/S2215-0366(19)30415-8
Brown, E. C., Clark, D. L., Forkert, N. D., Molnar, C. P., Kiss, Z. H. T., & Ramasubbu, R. (2020). Subcallosal cingulate metabolism predicts DBS response. Neuropsychopharmacology, 45(10), 1681–1688. https://doi.org/10.1038/s41386-020-0745-5
Mathers, C. D., & Loncar, D. (2006). Projections of global mortality and disease burden 2002–2030. PLOS Medicine, 3(11), Article e442. https://doi.org/10.1371/journal.pmed.0030442
Birmaher, B., Ryan, N. D., Williamson, D. E., Brent, D. A., Kaufman, J., Dahl, R. E., et al. (1996). Childhood and adolescent depression: Review. Journal of the American Academy of Child & Adolescent Psychiatry, 35(11), 1427–1439. https://doi.org/10.1097/00004583-199611000-00011
Scott, K., Lewis, C. C., & Marti, C. N. (2019). Trajectories of symptom change in TADS. Journal of the American Academy of Child & Adolescent Psychiatry, 58(3), 319–328. https://doi.org/10.1016/j.jaac.2018.07.908
Jeon, L., Buettner, C. K., & Snyder, A. R. (2014). Pathways from teacher depression to child behavioral problems. Journal of Consulting and Clinical Psychology, 82(2), 225–235. https://doi.org/10.1037/a0035720
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