{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:08:33Z","timestamp":1788394113785,"version":"build-2803163510"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,10]]},"DOI":"10.7759\/cureus.53987","type":"journal-article","created":{"date-parts":[[2024,2,11]],"date-time":"2024-02-11T04:41:56Z","timestamp":1707626516000},"source":"Crossref","is-referenced-by-count":12,"title":["Exploring Esketamine's Therapeutic Outcomes as an FDA-Designated Breakthrough for Treatment-Resistant Depression and Major Depressive Disorder With Suicidal Intent: A Narrative Review"],"prefix":"10.7759","author":[{"given":"Suneeta","family":"Kumari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan A","family":"Chaudhry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Sagot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy","family":"Doumas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussain","family":"Abdullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Alcera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Solhkhah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saba","family":"Afzal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","reference":[{"key":"ref1","unstructured":"World Health Organization. Depression GBD results Institute for Health Metrics and Evaluation. (2023). Accessed: March 4, 2023: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/depression.."},{"key":"ref2","article-title":"Socio-economic variations in the mental health treatment gap for people with anxiety, mood, and substance use disorders: results from the WHO World Mental Health (WMH) surveys","volume":"48(9)","author":"Evans-Lacko S","year":"2018","unstructured":"Evans-Lacko S, Aguilar-Gaxiola, Al-Hamzawi. Socio-economic variations in the mental health treatment gap for people with anxiety, mood, and substance use disorders: results from the WHO World Mental Health (WMH) surveys. Psychol Med. 2018, 48(9):1560-1571.","journal-title":"Psychol Med"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1002\/wps.21120","article-title":"Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventions","volume":"22","author":"McIntyre RS","year":"2023","unstructured":"McIntyre RS, Alsuwaidan M, Baune BT, et al.. Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventions. World Psychiatry. 2023, 22:394-412. 10.1002\/wps.21120","journal-title":"World Psychiatry"},{"key":"ref4","unstructured":"SPRAVATO\u00ae (Esketamine). Homepage. (2021). Accessed: December 31, 2023: https:\/\/www.spravato.com\/."},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1097\/EJA.0000000000000638","article-title":"History of anaesthesia: The ketamine story - past, present and future","volume":"34","author":"Mion G","year":"2017","unstructured":"Mion G. History of anaesthesia: The ketamine story - past, present and future. Eur J Anaesthesiol. 2017, 34:571-5. 10.1097\/EJA.0000000000000638","journal-title":"Eur J Anaesthesiol"},{"key":"ref6","article-title":"Ketamine: 50 years of modulating the mind. Frontiers in Human Neuroscience.","author":"Li L","year":"2016","unstructured":"Li L, Vlisides PE. Ketamine: 50 years of modulating the mind. Frontiers in Human Neuroscience.. 2016,"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.4103\/0259-1162.143110","article-title":"Ketamine: Current applications in anesthesia, pain, and critical care","volume":"8","author":"Kurdi MS","year":"2014","unstructured":"Kurdi MS, Theerth KA, Deva RS. Ketamine: Current applications in anesthesia, pain, and critical care. Anesth Essays Res. 2014, 8:283-90. 10.4103\/0259-1162.143110","journal-title":"Anesth Essays Res"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-018-0519-3","article-title":"Antidepressant efficacy and tolerability of ketamine and esketamine: a critical review","volume":"32","author":"Molero P","year":"2018","unstructured":"Molero P, Ramos-Quiroga JA, Martin-Santos R, Calvo-S\u00e1nchez E, Guti\u00e9rrez-Rojas L, Meana JJ. Antidepressant efficacy and tolerability of ketamine and esketamine: a critical review. CNS Drugs. 2018, 32:411-20. 10.1007\/s40263-018-0519-3","journal-title":"CNS Drugs"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2017.3739","article-title":"Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: a randomized clinical trial","volume":"75","author":"Daly EJ","year":"2018","unstructured":"Daly EJ, Singh JB, Fedgchin M, et al.. Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2018, 75:139-48. 10.1001\/jamapsychiatry.2017.3739","journal-title":"JAMA Psychiatry"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyz039","article-title":"Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: results of a randomized, double-blind, active-controlled study (TRANSFORM-1)","volume":"22","author":"Fedgchin M","year":"2019","unstructured":"Fedgchin M, Trivedi M, Daly EJ, et al.. Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: results of a randomized, double-blind, active-controlled study (TRANSFORM-1). Int J Neuropsychopharmacol. 2019, 22:616-30. 10.1093\/ijnp\/pyz039","journal-title":"Int J Neuropsychopharmacol"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2019.19020172","article-title":"Efficacy and safety of flexibly dosed Esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: a randomized double-blind active-controlled study","volume":"176","author":"Popova V","year":"2019","unstructured":"Popova V, Daly EJ, Trivedi M, et al.. Efficacy and safety of flexibly dosed Esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: a randomized double-blind active-controlled study. Am J Psychiatry. 2019, 176:428-38. 10.1176\/appi.ajp.2019.19020172","journal-title":"Am J Psychiatry"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jagp.2019.10.008","article-title":"Efficacy and safety of esketamine nasal spray plus an oral antidepressant in elderly patients with treatment-resistant depression\u2014TRANSFORM-3","volume":"28","author":"Ochs-Ross R","year":"2020","unstructured":"Ochs-Ross R, Daly EJ, Zhang Y, et al.. Efficacy and safety of esketamine nasal spray plus an oral antidepressant in elderly patients with treatment-resistant depression\u2014TRANSFORM-3. Am J Geriatr Psychiatry. 2020, 28:121-41. 10.1016\/j.jagp.2019.10.008","journal-title":"Am J Geriatr Psychiatry"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2019.1189","article-title":"Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial","volume":"76","author":"Daly EJ","year":"2019","unstructured":"Daly EJ, Trivedi MH, Janik A, et al.. Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2019, 76:893-903. 10.1001\/jamapsychiatry.2019.1189","journal-title":"JAMA Psychiatry"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.19m12891","article-title":"Esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression: assessment of long-term safety in a phase 3, open-label study (SUSTAIN-2)","volume":"81","author":"Wajs E","year":"2020","unstructured":"Wajs E, Aluisio L, Holder R, et al.. Esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression: assessment of long-term safety in a phase 3, open-label study (SUSTAIN-2). J Clin Psychiatry. 2020, 81:10.4088\/JCP.19m12891","journal-title":"J Clin Psychiatry"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-023-01577-5","article-title":"Long-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: interim results of the SUSTAIN-3 study","volume":"48","author":"Zaki N","year":"2023","unstructured":"Zaki N, Chen LN, Lane R, et al.. Long-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: interim results of the SUSTAIN-3 study. Neuropsychopharmacology. 2023, 48:1225-33. 10.1038\/s41386-023-01577-5","journal-title":"Neuropsychopharmacology"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2018.17060720","article-title":"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","volume":"175","author":"Canuso CM","year":"2018","unstructured":"Canuso CM, Singh JB, Fedgchin 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. Am J Psychiatry. 2018, 175:620-30. 10.1176\/appi.ajp.2018.17060720","journal-title":"Am J Psychiatry"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.19m13191","article-title":"Esketamine nasal spray for rapid reduction of major depressive disorder symptoms in patients who have active suicidal ideation with intent (ASPIRE I)","volume":"81","author":"Fu DJ","year":"2020","unstructured":"Fu DJ, Ionescu DF, Li X, et al.. Esketamine nasal spray for rapid reduction of major depressive disorder symptoms in patients who have active suicidal ideation with intent (ASPIRE I). J Clin Psychiatry. 2020, 81:10.4088\/JCP.19m13191","journal-title":"J Clin Psychiatry"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyaa068","article-title":"Esketamine nasal spray for rapid reduction of depressive symptoms in patients with major depressive disorder who have active suicide Ideation with Intent: results of a Phase 3, Double-Blind, randomized study (ASPIRE II)","volume":"24","author":"Ionescu DF","year":"2021","unstructured":"Ionescu DF, Fu DJ, Qiu X, et al.. Esketamine nasal spray for rapid reduction of depressive symptoms in patients with major depressive disorder who have active suicide Ideation with Intent: results of a Phase 3, Double-Blind, randomized study (ASPIRE II). Int J Neuropsychopharmacol. 2021, 24:22-31. 10.1093\/ijnp\/pyaa068","journal-title":"Int J Neuropsychopharmacol"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0000000000001465","article-title":"Esketamine nasal spray for the rapid reduction of depressive symptoms in major depressive disorder with acute suicidal ideation or behavior","volume":"41","author":"Canuso CM","year":"2021","unstructured":"Canuso CM, Ionescu DF, Li X, et al.. Esketamine nasal spray for the rapid reduction of depressive symptoms in major depressive disorder with acute suicidal ideation or behavior. J Clin Psychopharmacol. 2021, 41:516-24. 10.1097\/JCP.0000000000001465","journal-title":"J Clin Psychopharmacol"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2015.10.018","article-title":"Intravenous esketamine in adult treatment-resistant depression: a double-blind, double-randomization, placebo-controlled study","volume":"80","author":"Singh JB","year":"2016","unstructured":"Singh JB, Fedgchin M, Daly E, et al.. Intravenous esketamine in adult treatment-resistant depression: a double-blind, double-randomization, placebo-controlled study. Biol Psychiatry. 2016, 80:424-31. 10.1016\/j.biopsych.2015.10.018","journal-title":"Biol Psychiatry"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2019.11.086","article-title":"Efficacy and safety of adjunctive therapy using esketamine or racemic ketamine for adult treatment-resistant depression: A randomized, double-blind, non-inferiority study","volume":"264","author":"Correia-Melo FS","year":"2020","unstructured":"Correia-Melo FS, Leal GC, Vieira F, et al.. Efficacy and safety of adjunctive therapy using esketamine or racemic ketamine for adult treatment-resistant depression: A randomized, double-blind, non-inferiority study. J Affect Disord. 2020, 264:527-34. 10.1016\/j.jad.2019.11.086","journal-title":"J Affect Disord"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2019.01.017","article-title":"Comparability of blinded remote and site-based assessments of response to adjunctive esketamine or placebo nasal spray in patients with treatment resistant depression","volume":"111","author":"Targum SD","year":"2019","unstructured":"Targum SD, Daly E, Fedgchin M, Cooper K, Singh JB. Comparability of blinded remote and site-based assessments of response to adjunctive esketamine or placebo nasal spray in patients with treatment resistant depression. J Psychiatr Res. 2019, 111:68-73. 10.1016\/j.jpsychires.2019.01.017","journal-title":"J Psychiatr Res"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-018-4828-5","article-title":"Effect of intranasal esketamine on cognitive functioning in healthy participants: a randomized, double-blind, placebo-controlled study","volume":"235","author":"Morrison RL","year":"2018","unstructured":"Morrison RL, Fedgchin M, Singh J, et al.. Effect of intranasal esketamine on cognitive functioning in healthy participants: a randomized, double-blind, placebo-controlled study. Psychopharmacology (Berl). 2018, 235:1107-19. 10.1007\/s00213-018-4828-5","journal-title":"Psychopharmacology (Berl)"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-017-4706-6","article-title":"The effects of intranasal esketamine (84 mg) and oral mirtazapine (30 mg) on on-road driving performance: a double-blind, placebo-controlled study","volume":"234","author":"van de Loo AJ","year":"2017","unstructured":"van de Loo AJ, Bervoets AC, Mooren L, et al.. The effects of intranasal esketamine (84 mg) and oral mirtazapine (30 mg) on on-road driving performance: a double-blind, placebo-controlled study. Psychopharmacology (Berl). 2017, 234:3175-83. 10.1007\/s00213-017-4706-6","journal-title":"Psychopharmacology (Berl)"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1177\/2042098620937899","article-title":"Esketamine: new hope for the treatment of treatment-resistant depression? A narrative review","volume":"11","author":"Salahudeen MS","year":"2020","unstructured":"Salahudeen MS, Wright CM, Peterson GM. Esketamine: new hope for the treatment of treatment-resistant depression? A narrative review. Ther Adv Drug Saf. 2020, 11:2042098620937899. 10.1177\/2042098620937899","journal-title":"Ther Adv Drug Saf"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1016\/s0006-3223(99)00230-9","article-title":"Antidepressant effects of ketamine in depressed patients","volume":"47","author":"Berman R","year":"2000","unstructured":"Berman R, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biological Psychiatry. 2000, 47:351-4. 10.1016\/s0006-3223(99)00230-9","journal-title":"Biological Psychiatry"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2016.16010037","article-title":"A double-blind, randomized, placebo-controlled, dose-frequency study of intravenous ketamine in patients with treatment-resistant depression","volume":"173","author":"Singh JB","year":"2016","unstructured":"Singh JB, Fedgchin M, Daly EJ, et al.. A double-blind, randomized, placebo-controlled, dose-frequency study of intravenous ketamine in patients with treatment-resistant depression. Am J Psychiatry. 2016, 173:816-26. 10.1176\/appi.ajp.2016.16010037","journal-title":"Am J Psychiatry"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2023.11810","article-title":"Esketamine for treatment\u2011resistant depression: A review of clinical evidence (Review)","volume":"25","author":"Vasiliu O","year":"2023","unstructured":"Vasiliu O. Esketamine for treatment\u2011resistant depression: A review of clinical evidence (Review). Exp Ther Med. 2023, 25:111. 10.3892\/etm.2023.11810","journal-title":"Exp Ther Med"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.2147\/ndt. s388392","article-title":"Early clinical experiences of esketamine nasal spray in the UK in adults with treatment-resistant major depressive disorder: advisory panel recommendations","volume":"19","author":"Young AH","year":"2023","unstructured":"Young AH, Abdelghani M, Juruena MF, Nikolova VL, Nilforooshan R. Early clinical experiences of esketamine nasal spray in the UK in adults with treatment-resistant major depressive disorder: advisory panel recommendations. Neuro Dis Trea. 2023, 19:433-41. 10.2147\/ndt. s388392","journal-title":"Neuro Dis Trea"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.9758\/cpn.2021.19.2.341","article-title":"Rapid onset of intranasal esketamine in patients with treatment resistant depression and major depression with suicide ideation: a meta-analysis","volume":"19","author":"Wang SM","year":"2021","unstructured":"Wang SM, Kim NY, Na HR, Lim HK, Woo YS, Pae CU, Bahk WM. Rapid onset of intranasal esketamine in patients with treatment resistant depression and major depression with suicide ideation: a meta-analysis. Clin Psychopharmacol Neurosci. 2021, 19:341-54. 10.9758\/cpn.2021.19.2.341","journal-title":"Clin Psychopharmacol Neurosci"},{"key":"ref31","unstructured":"Cleveland Clinic. Professional CCM Treatment-Resistant depression. (2024). Accessed: February 6, 2024: https:\/\/my.clevelandclinic.org\/health\/diseases\/24991-treatment-resistant-depression.."},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2304145","article-title":"Esketamine nasal spray versus quetiapine for treatment-resistant depression","volume":"389","author":"Reif A","year":"2023","unstructured":"Reif A, Bitter I, Buyze J, et al.. Esketamine nasal spray versus quetiapine for treatment-resistant depression. N Engl J Med. 2023, 389:1298-309. 10.1056\/NEJMoa2304145","journal-title":"N Engl J Med"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.03.026","article-title":"Hydrogel-forming microneedle arrays as a therapeutic option for transdermal esketamine delivery","volume":"322","author":"Courtenay AJ","year":"2020","unstructured":"Courtenay AJ, McAlister E, McCrudden MT, et al.. Hydrogel-forming microneedle arrays as a therapeutic option for transdermal esketamine delivery. J Control Release. 2020, 322:177-86. 10.1016\/j.jconrel.2020.03.026","journal-title":"J Control Release"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2020.20081251","article-title":"Synthesizing the evidence for ketamine and esketamine in treatment-resistant depression: an international expert opinion on the available evidence and implementation","volume":"178","author":"McIntyre RS","year":"2021","unstructured":"McIntyre RS, Rosenblat JD, Nemeroff CB, et al.. Synthesizing the evidence for ketamine and esketamine in treatment-resistant depression: an international expert opinion on the available evidence and implementation. Am J Psychiatry. 2021, 178:383-99. 10.1176\/appi.ajp.2020.20081251","journal-title":"Am J Psychiatry"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01652-1","article-title":"Blood-based biomarkers of antidepressant response to ketamine and esketamine: A systematic review and meta-analysis","volume":"27","author":"Medeiros GC","year":"2022","unstructured":"Medeiros GC, Gould TD, Prueitt WL, et al.. Blood-based biomarkers of antidepressant response to ketamine and esketamine: A systematic review and meta-analysis. Mol Psychiatry. 2022, 27:3658-69. 10.1038\/s41380-022-01652-1","journal-title":"Mol Psychiatry"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.2147\/JEP.S259302","article-title":"Experimental therapeutics in treatment-resistant major depressive disorder","volume":"13","author":"Kaur M","year":"2021","unstructured":"Kaur M, Sanches M. Experimental therapeutics in treatment-resistant major depressive disorder. J Exp Pharmacol. 2021, 13:181-96. 10.2147\/JEP.S259302","journal-title":"J Exp Pharmacol"},{"key":"ref37","unstructured":"World Health Organization. Mental health of adolescents. (2021). Accessed: January 30, 2023: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/adolescent-mental-health."},{"key":"ref38","unstructured":"ClinicalTrials. Homepage. (2024). Accessed: February 6, 2024: https:\/\/clinicaltrials.gov\/."}],"container-title":["Cureus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cureus.com\/articles\/207911-exploring-esketamines-therapeutic-outcomes-as-an-fda-designated-breakthrough-for-treatment-resistant-depression-and-major-depressive-disorder-with-suicidal-intent-a-narrative-review","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,11]],"date-time":"2024-02-11T04:42:02Z","timestamp":1707626522000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cureus.com\/articles\/207911-exploring-esketamines-therapeutic-outcomes-as-an-fda-designated-breakthrough-for-treatment-resistant-depression-and-major-depressive-disorder-with-suicidal-intent-a-narrative-review"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,10]]},"references-count":38,"URL":"https:\/\/doi.org\/10.7759\/cureus.53987","relation":{},"ISSN":["2168-8184"],"issn-type":[{"value":"2168-8184","type":"print"}],"subject":[],"published":{"date-parts":[[2024,2,10]]}}}