{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T13:54:01Z","timestamp":1793627641608,"version":"4.5.1"},"reference-count":117,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2024,7,13]],"date-time":"2024-07-13T00:00:00Z","timestamp":1720828800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,13]],"date-time":"2024-07-13T00:00:00Z","timestamp":1720828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur Arch Psychiatry Clin Neurosci"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>The discovery of racemic (<jats:italic>R<\/jats:italic>,<jats:italic> S<\/jats:italic>)-ketamine as a rapid-acting antidepressant and the subsequent FDA approval of its (<jats:italic>S<\/jats:italic>)-enantiomer, esketamine, for treatment-resistant depression (TRD) are significant advances in the development of novel neuropsychiatric therapeutics. Esketamine is now recognized as a powerful tool for addressing persistent symptoms of TRD compared to traditional oral antidepressants. However, research on biomarkers associated with antidepressant response to esketamine has remained sparse and, to date, has been largely extrapolated from racemic ketamine studies. Genetic, proteomic, and metabolomic profiles suggest that inflammation and mitochondrial function may play a role in esketamine\u2019s antidepressant effects, though these preliminary results require verification. In addition, neuroimaging research has consistently implicated the prefrontal cortex, striatum, and anterior cingulate cortex in esketamine\u2019s effects. Esketamine also shows promise in perioperative settings for reducing depression and anxiety, and these effects appear to correlate with increased peripheral biomarkers such as brain-derived neurotrophic factor and serotonin. Further indications are likely to be identified with the continued repurposing of racemic ketamine, providing further opportunity for biomarker study and mechanistic understanding of therapeutic effects. Novel methodologies and well-designed biomarker-focused clinical research trials are needed to more clearly elucidate esketamine\u2019s therapeutic actions as well as biologically identify those most likely to benefit from this agent, allowing for the improved personalization of antidepressant treatment.<\/jats:p>","DOI":"10.1007\/s00406-024-01865-1","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T23:24:05Z","timestamp":1720826645000},"page":"1559-1572","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Esketamine in depression: putative biomarkers from clinical research"],"prefix":"10.1007","volume":"275","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2986-3179","authenticated-orcid":false,"given":"Jenessa N.","family":"Johnston","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4442-7412","authenticated-orcid":false,"suffix":"Jr.","given":"Carlos A.","family":"Zarate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1093-1648","authenticated-orcid":false,"given":"Mark D.","family":"Kvarta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,13]]},"reference":[{"key":"1865_CR1","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1097\/EJA.0000000000000638","volume":"34","author":"G Mion","year":"2017","unstructured":"Mion G (2017) History of anaesthesia: the ketamine story \u2013 past, present and future. Eur J Anaesthesiol 34:571\u2013575","journal-title":"Eur J Anaesthesiol"},{"key":"1865_CR2","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1016\/S0022-3565(25)38235-2","volume":"265","author":"G Nowak","year":"1993","unstructured":"Nowak G, Trullas R, Layer RT, Skolnick P, Paul IA (1993) Adaptive changes in the n-methyl-d-aspartate receptor complex after chronic treatment with imipramine and 1-aminocyclopropanecarboxylic acid. J Pharmacol Exp Ther 265:1380\u20131386","journal-title":"J Pharmacol Exp Ther"},{"key":"1865_CR3","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/S0006-3223(99)00230-9","volume":"47","author":"RM Berman","year":"2000","unstructured":"Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 47:351\u2013354","journal-title":"Biol Psychiatry"},{"key":"1865_CR4","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1016\/j.biopsych.2011.12.010","volume":"71","author":"CA Zarate Jr","year":"2012","unstructured":"Zarate CA Jr., Brutsche NE, Ibrahim L, Franco-Chaves J, Diazgranados N, Cravchik A, Selter J, Marquardt CA, Liberty V, Luckenbaugh DA (2012) Replication of ketamine\u2019s antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry 71:939\u2013946","journal-title":"Biol Psychiatry"},{"key":"1865_CR5","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1001\/archpsyc.63.8.856","volume":"63","author":"CA Zarate Jr","year":"2006","unstructured":"Zarate CA Jr., Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK (2006) A randomized trial of an n-methyl-d-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63:856\u2013864","journal-title":"Arch Gen Psychiatry"},{"key":"1865_CR6","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1038\/mp.2017.255","volume":"23","author":"P Zanos","year":"2018","unstructured":"Zanos P, Gould TD (2018) Mechanisms of ketamine action as an antidepressant. Mol Psychiatry 23:801\u2013811","journal-title":"Mol Psychiatry"},{"key":"1865_CR7","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1111\/j.1460-9592.2007.02384.x","volume":"18","author":"DW Herd","year":"2008","unstructured":"Herd DW, Anderson BJ, Keene NA, Holford NH (2008) Investigating the pharmacodynamics of ketamine in children. Paediatr Anaesth 18:36\u201342","journal-title":"Paediatr Anaesth"},{"key":"1865_CR8","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1152\/jn.1987.58.2.251","volume":"58","author":"J MacDonald","year":"1987","unstructured":"MacDonald J, Miljkovic Z, Pennefather P (1987) Use-dependent block of excitatory amino acid currents in cultured neurons by ketamine. J Neurophysiol 58:251\u2013266","journal-title":"J Neurophysiol"},{"key":"1865_CR9","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1073\/pnas.85.4.1307","volume":"85","author":"JE Huettner","year":"1988","unstructured":"Huettner JE, Bean BP (1988) Block of n-methyl-d-aspartate-activated current by the anticonvulsant mk-801: selective binding to open channels. Proc Natl Acad Sci 85:1307\u20131311","journal-title":"Proc Natl Acad Sci"},{"key":"1865_CR10","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.3109\/00498254.2012.685777","volume":"42","author":"Z Desta","year":"2012","unstructured":"Desta Z, Moaddel R, Ogburn ET, Xu C, Ramamoorthy A, Venkata SLV, Sanghvi M, Goldberg ME, Torjman MC, Wainer IW (2012) Stereoselective and regiospecific hydroxylation of ketamine and norketamine. Xenobiotica 42:1076\u20131087","journal-title":"Xenobiotica"},{"key":"1865_CR11","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1097\/ALN.0000000000001392","volume":"125","author":"LK Rao","year":"2016","unstructured":"Rao LK, Flaker AM, Friedel CC, Kharasch ED (2016) Role of cytochrome p4502b6 polymorphisms in ketamine metabolism and clearance. Anesthesiology 125:1103\u20131112","journal-title":"Anesthesiology"},{"key":"1865_CR12","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/clpt.1984.235","volume":"36","author":"EF Domino","year":"1984","unstructured":"Domino EF, Domino SE, Smith RE, Domino LE, Goulet JR, Domino KE, Zsigmond EK (1984) Ketamine kinetics in unmedicated and diazepam-premedicated subjects. Clin Pharmacol Ther 36:645\u2013653","journal-title":"Clin Pharmacol Ther"},{"key":"1865_CR13","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/BF01066320","volume":"15","author":"J Sch\u00fcttler","year":"1987","unstructured":"Sch\u00fcttler J, Stanski DR, White PF, Trevor AJ, Horai Y, Verotta D, Sheiner LB (1987) Pharmacodynamic modeling of the eeg effects of ketamine and its enantiomers in man. J Pharmacokinet Biopharm 15:241\u2013253","journal-title":"J Pharmacokinet Biopharm"},{"key":"1865_CR14","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1097\/ALN.0b013e3181b437b1","volume":"111","author":"M Sigtermans","year":"2009","unstructured":"Sigtermans M, Dahan A, Mooren R, Bauer M, Kest B, Sarton E, Olofsen E (2009) S (+)-ketamine effect on experimental pain and cardiac output: a population pharmacokinetic-pharmacodynamic modeling study in healthy volunteers. Anesthesiology 111:892\u2013903","journal-title":"Anesthesiology"},{"key":"1865_CR15","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1093\/bja\/75.4.506","volume":"75","author":"G Geisslinger","year":"1995","unstructured":"Geisslinger G, Hering W, Kamp H, Vollmers K (1995) Pharmacokinetics of ketamine enantiomers. Br J Anaesth 75:506\u2013507","journal-title":"Br J Anaesth"},{"key":"1865_CR16","doi-asserted-by":"publisher","first-page":"7942","DOI":"10.1016\/j.chroma.2010.06.028","volume":"1217","author":"S Portmann","year":"2010","unstructured":"Portmann S, Kwan HY, Theurillat R, Schmitz A, Mevissen M, Thormann W (2010) Enantioselective capillary electrophoresis for identification and characterization of human cytochrome p450 enzymes which metabolize ketamine and norketamine in vitro. J Chromatogr A 1217:7942\u20137948","journal-title":"J Chromatogr A"},{"key":"1865_CR17","first-page":"431","volume":"70","author":"H Ihmsen","year":"2001","unstructured":"Ihmsen H, Geisslinger G, Sch\u00fcttler J (2001) Stereoselective pharmacokinetics of ketamine: R (\u2013)-ketamine inhibits the elimination of s (+)\u2010ketamine. Clin Pharmacol Ther 70:431\u2013438","journal-title":"Clin Pharmacol Ther"},{"key":"1865_CR18","doi-asserted-by":"publisher","first-page":"108431","DOI":"10.1016\/j.pharmthera.2023.108431","volume":"246","author":"JN Johnston","year":"2023","unstructured":"Johnston JN, Henter ID, Zarate CA Jr (2023) The antidepressant actions of ketamine and its enantiomers. Pharmacol Ther 246:108431","journal-title":"Pharmacol Ther"},{"key":"1865_CR19","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.jad.2023.02.151","volume":"330","author":"GC Leal","year":"2023","unstructured":"Leal GC, Souza-Marques B, Mello RP, Bandeira ID, Caliman-Fontes AT, Carneiro BA, Faria-Guimar\u00e3es D, Guerreiro-Costa LN, Jesus-Nunes AP, Silva SS (2023) Arketamine as adjunctive therapy for treatment-resistant depression: a placebo-controlled pilot study. J Affect Disord 330:7\u201315","journal-title":"J Affect Disord"},{"key":"1865_CR20","unstructured":"Atai Life Sciences (2023) Atai life sciences announces results from phase 2a trial of pcn-101 (r-ketamine) for treatment-resistant depression. https:\/\/www.globenewswire.com\/news-release\/2023\/01\/06\/2584334\/0\/en\/atai-life-sciences-announces-results-from-phase-2a-trial-of-pcn-101-r-ketamine-for-treatment-resistant-depression.Html"},{"key":"1865_CR21","doi-asserted-by":"publisher","first-page":"109513","DOI":"10.1016\/j.celrep.2021.109513","volume":"36","author":"P-Y Lin","year":"2021","unstructured":"Lin P-Y, Ma ZZ, Mahgoub M, Kavalali ET, Monteggia LM (2021) A synaptic locus for trkb signaling underlying ketamine rapid antidepressant action. Cell Rep 36:109513","journal-title":"Cell Rep"},{"key":"1865_CR22","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.neuropharm.2015.07.028","volume":"100","author":"OH Miller","year":"2016","unstructured":"Miller OH, Moran JT, Hall BJ (2016) Two cellular hypotheses explaining the initiation of ketamine\u2019s antidepressant actions: direct inhibition and disinhibition. Neuropharmacology 100:17\u201326","journal-title":"Neuropharmacology"},{"key":"1865_CR23","doi-asserted-by":"publisher","first-page":"E3007","DOI":"10.1073\/pnas.1718883115","volume":"115","author":"AJ Widman","year":"2018","unstructured":"Widman AJ, McMahon LL (2018) Disinhibition of ca1 pyramidal cells by low-dose ketamine and other antagonists with rapid antidepressant efficacy. Proc Natl Acad Sci 115:E3007\u2013E3016","journal-title":"Proc Natl Acad Sci"},{"key":"1865_CR24","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/nature10130","volume":"475","author":"AE Autry","year":"2011","unstructured":"Autry AE, Adachi M, Nosyreva E, Na ES, Los MF, Cheng P-f, Kavalali ET, Monteggia LM (2011) Nmda receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 475:91\u201395","journal-title":"Nature"},{"key":"1865_CR25","doi-asserted-by":"publisher","first-page":"94","DOI":"10.3389\/fnmol.2014.00094","volume":"7","author":"E Nosyreva","year":"2014","unstructured":"Nosyreva E, Autry AE, Kavalali ET, Monteggia LM (2014) Age dependence of the rapid antidepressant and synaptic effects of acute nmda receptor blockade. Front Mol Neurosci 7:94","journal-title":"Front Mol Neurosci"},{"key":"1865_CR26","doi-asserted-by":"publisher","first-page":"6990","DOI":"10.1523\/JNEUROSCI.4998-12.2013","volume":"33","author":"E Nosyreva","year":"2013","unstructured":"Nosyreva E, Szabla K, Autry AE, Ryazanov AG, Monteggia LM, Kavalali ET (2013) Acute suppression of spontaneous neurotransmission drives synaptic potentiation. J Neurosci 33:6990\u20137002","journal-title":"J Neurosci"},{"key":"1865_CR27","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s10571-021-01180-6","volume":"43","author":"X Zhu","year":"2023","unstructured":"Zhu X, Zhang F, You Y, Wang H, Yuan S, Wu B, Zhu R, Liu D, Yan F, Wang Z (2023) S-ketamine exerts antidepressant effects by regulating rac1 gtpase mediated synaptic plasticity in the hippocampus of stressed rats. Cell Mol Neurobiol 43:299\u2013314","journal-title":"Cell Mol Neurobiol"},{"key":"1865_CR28","doi-asserted-by":"publisher","first-page":"6704","DOI":"10.1038\/s41380-021-01093-2","volume":"26","author":"J Bonaventura","year":"2021","unstructured":"Bonaventura J, Lam S, Carlton M, Boehm MA, Gomez JL, Sol\u00eds O, S\u00e1nchez-Soto M, Morris PJ, Fredriksson I, Thomas CJ (2021) Pharmacological and behavioral divergence of ketamine enantiomers: implications for abuse liability. Mol Psychiatry 26:6704\u20136722","journal-title":"Mol Psychiatry"},{"key":"1865_CR29","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1016\/j.biopsych.2022.12.019","volume":"93","author":"MR Levinstein","year":"2023","unstructured":"Levinstein MR, Carlton ML, Di Ianni T, Ventriglia EN, Rizzo A, Gomez JL, Budinich RC, Shaham Y, Airan RD, Zarate CA Jr (2023) Mu opioid receptor activation mediates (s)-ketamine reinforcement in rats: implications for abuse liability. Biol Psychiatry 93:1118\u20131126","journal-title":"Biol Psychiatry"},{"key":"1865_CR30","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/s41386-023-01652-x","volume":"49","author":"MR Levinstein","year":"2024","unstructured":"Levinstein MR, Michaelides M (2024) Exploring the role of mu opioid receptors in the therapeutic potential and abuse liability of (s)-ketamine. Neuropsychopharmacology 49:315\u2013316","journal-title":"Neuropsychopharmacology"},{"key":"1865_CR31","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1038\/s41380-019-0503-4","volume":"24","author":"NR Williams","year":"2019","unstructured":"Williams NR, Heifets BD, Bentzley BS, Blasey C, Sudheimer KD, Hawkins J, Lyons DM, Schatzberg AF (2019) Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism. Mol Psychiatry 24:1779\u20131786","journal-title":"Mol Psychiatry"},{"key":"1865_CR32","doi-asserted-by":"publisher","first-page":"2656","DOI":"10.1073\/pnas.1916570117","volume":"117","author":"ME Klein","year":"2020","unstructured":"Klein ME, Chandra J, Sheriff S, Malinow R (2020) Opioid system is necessary but not sufficient for antidepressive actions of ketamine in rodents. Proc Natl Acad Sci 117:2656\u20132662","journal-title":"Proc Natl Acad Sci"},{"key":"1865_CR33","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1097\/ADM.0000000000000929","volume":"16","author":"C Hailozian","year":"2022","unstructured":"Hailozian C, Luftig J, Liang A, Outhay M, Ullal M, Anderson ES, Kalmin M, Shoptaw S, Greenwald MK, Herring AA (2022) Synergistic effect of ketamine and buprenorphine observed in the treatment of buprenorphine precipitated opioid withdrawal in a patient with fentanyl use. J Addict Med 16:483\u2013487","journal-title":"J Addict Med"},{"key":"1865_CR34","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.tins.2018.12.002","volume":"42","author":"Y Cui","year":"2019","unstructured":"Cui Y, Hu S, Hu H (2019) Lateral habenular burst firing as a target of the rapid antidepressant effects of ketamine. Trends Neurosci 42:179\u2013191","journal-title":"Trends Neurosci"},{"key":"1865_CR35","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1038\/s41586-023-06624-1","volume":"622","author":"S Ma","year":"2023","unstructured":"Ma S, Chen M, Jiang Y, Xiang X, Wang S, Wu Z, Li S, Cui Y, Wang J, Zhu Y, Zhang Y, Ma H, Duan S, Li H, Yang Y, Lingle CJ, Hu H (2023) Sustained antidepressant effect of ketamine through nmdar trapping in the lhb. Nature 622:802\u2013809","journal-title":"Nature"},{"key":"1865_CR36","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1038\/s41386-020-0644-9","volume":"45","author":"CG Abdallah","year":"2020","unstructured":"Abdallah CG, Averill LA, Gueorguieva R, Goktas S, Purohit P, Ranganathan M, Sherif M, Ahn K-H, D\u2019Souza DC, Formica R (2020) Modulation of the antidepressant effects of ketamine by the mtorc1 inhibitor rapamycin. Neuropsychopharmacology 45:990\u2013997","journal-title":"Neuropsychopharmacology"},{"key":"1865_CR37","first-page":"320","volume":"51","author":"L Harding","year":"2023","unstructured":"Harding L (2023) Regulating ketamine use in psychiatry. J Am Acad Psychiatry Law 51:320\u2013325","journal-title":"J Am Acad Psychiatry Law"},{"key":"1865_CR38","doi-asserted-by":"publisher","first-page":"433","DOI":"10.2147\/NDT.S388392","volume":"19","author":"AH Young","year":"2023","unstructured":"Young AH, Abdelghani M, Juruena MF, Nikolova VL, Nilforooshan R (2023) Early clinical experiences of esketamine nasal spray in the Uk in adults with treatment-resistant major depressive disorder: Advisory panel recommendations. Neuropsychiatr Dis Treat 19:433\u2013441","journal-title":"Neuropsychiatr Dis Treat"},{"key":"1865_CR39","unstructured":"New Zealand Medicines and Medical Devices Safety Authority (2019) Medsafe classification database. Https:\/\/medsafe.Govt.Nz\/profs\/class\/classintro.Asp"},{"key":"1865_CR40","volume-title":"Therapeutic goods administration","author":"Australian Government Department of Health and Aged Care","year":"2024","unstructured":"Australian Government Department of Health and Aged Care (2024) Therapeutic goods administration. Https:\/\/www.Tga.Gov.Au, Available at"},{"key":"1865_CR41","unstructured":"European Medicines Agency (EMA) (2019) Spravato. Https:\/\/www.Ema.Europa.Eu\/en\/medicines\/human\/epar\/spravato. 2024"},{"key":"1865_CR42","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1001\/jamapsychiatry.2017.0080","volume":"74","author":"G Sanacora","year":"2017","unstructured":"Sanacora G, Frye MA, McDonald W, Mathew SJ, Turner MS, Schatzberg AF, Summergrad P, Nemeroff CB, American Psychiatric Association (APA) Council of Research Task Force on Novel Biomarkers and Treatments (2017) A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry 74:399\u2013405","journal-title":"JAMA Psychiatry"},{"key":"1865_CR43","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1176\/appi.ajp.2018.18030290","volume":"175","author":"R Freedman","year":"2018","unstructured":"Freedman R, Brown AS, Cannon TD, Druss BJ, Earls FJ, Escobar J, Hurd YL, Lewis DA, L\u00f3pez-Jaramillo C, Luby J, Mayberg HS, Moffitt TE, Oquendo M, Perlis RH, Pine DS, Rush AJ, Tamminga CA, Tohen M, Vieta E, Wisner KL, Xin Y (2018) Can a framework be established for the safe use of ketamine? Am J Psychiatry 175:587\u2013589","journal-title":"Am J Psychiatry"},{"key":"1865_CR44","unstructured":"Drug Enforcement Agency (DEA) (2024) Ketamine. Https:\/\/www.Deadiversion.Usdoj.Gov\/drug_chem_info\/ketamine.Pdf. 2024"},{"key":"1865_CR45","doi-asserted-by":"publisher","first-page":"87","DOI":"10.25122\/jml-2020-0116","volume":"14","author":"M Alipoor","year":"2021","unstructured":"Alipoor M, Loripoor M, Kazemi M, Farahbakhsh F, Sarkoohi A (2021) The effect of ketamine on preventing postpartum depression. J Med Life 14:87","journal-title":"J Med Life"},{"key":"1865_CR46","doi-asserted-by":"publisher","first-page":"e078218","DOI":"10.1136\/bmj-2023-078218","volume":"385","author":"S Wang","year":"2024","unstructured":"Wang S, Deng C-M, Zeng Y, Chen X-Z, Li A-Y, Feng S-W, Xu L-L, Chen L, Yuan H-M, Hu H (2024) Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial. BMJ 385:e078218","journal-title":"BMJ"},{"key":"1865_CR47","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/s41386-023-01632-1","volume":"49","author":"JN Johnston","year":"2024","unstructured":"Johnston JN, Kadriu B, Kraus C, Henter ID, Zarate CA Jr (2024) Ketamine in neuropsychiatric disorders: an update. Neuropsychopharmacology 49:23\u201340","journal-title":"Neuropsychopharmacology"},{"key":"1865_CR48","doi-asserted-by":"publisher","first-page":"372390","DOI":"10.3389\/fpsyt.2018.00277","volume":"9","author":"JL Jones","year":"2018","unstructured":"Jones JL, Mateus CF, Malcolm RJ, Brady KT, Back SE (2018) Efficacy of ketamine in the treatment of substance use disorders: a systematic review. Front Psychiatry 9:372390","journal-title":"Front Psychiatry"},{"key":"1865_CR49","doi-asserted-by":"publisher","first-page":"4158","DOI":"10.3390\/nu13114158","volume":"13","author":"JL Keeler","year":"2021","unstructured":"Keeler JL, Treasure J, Juruena MF, Kan C, Himmerich H (2021) Ketamine as a treatment for anorexia nervosa: a narrative review. Nutrients 13:4158","journal-title":"Nutrients"},{"key":"1865_CR50","doi-asserted-by":"publisher","first-page":"e107","DOI":"10.1192\/bjo.2024.62","volume":"10","author":"LA Jelen","year":"2024","unstructured":"Jelen LA, McShane R, Young AH (2024) Guidelines for ketamine use in clinical psychiatry practice. BJPsych Open 10:e107","journal-title":"BJPsych Open"},{"key":"1865_CR51","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1016\/j.biopsych.2014.03.026","volume":"76","author":"KA Lapidus","year":"2014","unstructured":"Lapidus KA, Levitch CF, Perez AM, Brallier JW, Parides MK, Soleimani L, Feder A, Iosifescu DV, Charney DS, Murrough JW (2014) A randomized controlled trial of intranasal ketamine in major depressive disorder. Biol Psychiatry 76:970\u2013976","journal-title":"Biol Psychiatry"},{"key":"1865_CR52","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1212\/WNL.55.1.139","volume":"55","author":"H Kaube","year":"2000","unstructured":"Kaube H, Herzog J, Kaufer T, Dichgans M, Diener H (2000) Aura in some patients with familial hemiplegic migraine can be stopped by intranasal ketamine. Neurology 55:139\u2013141","journal-title":"Neurology"},{"key":"1865_CR53","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.ejpain.2009.08.002","volume":"14","author":"V Huge","year":"2010","unstructured":"Huge V, Lauchart M, Magerl W, Schelling G, Beyer A, Thieme D, Azad SC (2010) Effects of low-dose intranasal (s)-ketamine in patients with neuropathic pain. Eur J Pain 14:387\u2013394","journal-title":"Eur J Pain"},{"key":"1865_CR54","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.pain.2003.07.001","volume":"108","author":"DB Carr","year":"2004","unstructured":"Carr DB, Goudas LC, Denman WT, Brookoff D, Staats PS, Brennen L, Green G, Albin R, Hamilton D, Rogers MC (2004) Safety and efficacy of intranasal ketamine for the treatment of breakthrough pain in patients with chronic pain: a randomized, double-blind, placebo-controlled, crossover study. Pain 108:17\u201327","journal-title":"Pain"},{"key":"1865_CR55","doi-asserted-by":"publisher","first-page":"10108","DOI":"10.4088\/JCP.17f11567","volume":"78","author":"C Andrade","year":"2017","unstructured":"Andrade C (2017) Ketamine for depression, 1: clinical summary of issues related to efficacy, adverse effects, and mechanism of action. J Clin Psychiatry 78:10108","journal-title":"J Clin Psychiatry"},{"key":"1865_CR56","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.jad.2023.12.038","volume":"348","author":"G d\u2019Andrea","year":"2024","unstructured":"d\u2019Andrea G, Pettorruso M, Di Lorenzo G, Rhee TG, Chiappini S, Carullo R, Barlati S, Zanardi R, Rosso G, Di Nicola M (2024) The rapid antidepressant effectiveness of repeated dose of intravenous ketamine and intranasal esketamine: a post-hoc analysis of pooled real-world data. J Affect Disord 348:314\u2013322","journal-title":"J Affect Disord"},{"key":"1865_CR57","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.jad.2019.11.086","volume":"264","author":"FS Correia-Melo","year":"2020","unstructured":"Correia-Melo FS, Leal GC, Vieira F, Jesus-Nunes AP, Mello RP, Magnavita G, Caliman-Fontes AT, Echegaray MV, Bandeira ID, Silva SS (2020) 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 264:527\u2013534","journal-title":"J Affect Disord"},{"key":"1865_CR58","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1001\/jamapsychiatry.2022.1074","volume":"79","author":"S Nikayin","year":"2022","unstructured":"Nikayin S, Rhee TG, Cunningham ME (2022) Evaluation of the trajectory of depression severity with ketamine and esketamine in a clinical setting. JAMA Psychiatry 79:736\u2013738","journal-title":"JAMA Psychiatry"},{"key":"1865_CR59","doi-asserted-by":"publisher","first-page":"22m14548","DOI":"10.4088\/JCP.22m14548","volume":"84","author":"B Singh","year":"2023","unstructured":"Singh B, Kung S, Pazdernik V, Schak KM, Geske J, Schulte PJ, Frye MA, Vande Voort JL (2023) Comparative effectiveness of intravenous ketamine and intranasal esketamine in clinical practice among patients with treatment-refractory depression: an observational study. J Clin Psychiatry 84:22m14548","journal-title":"J Clin Psychiatry"},{"key":"1865_CR60","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1016\/j.jad.2024.04.088","volume":"356","author":"B Singh","year":"2024","unstructured":"Singh B, Kung S, Vande Voort JL (2024) Intravenous (iv) ketamine versus intranasal esketamine for depression \u2014 advantage iv ketamine? J Affect Disord 356:564\u2013567","journal-title":"J Affect Disord"},{"key":"1865_CR61","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1016\/j.jad.2024.04.039","volume":"356","author":"CN Calder","year":"2024","unstructured":"Calder CN, Kwan ATH, Teopiz KM, Wong S, Rosenblat JD, Mansur RB, Rhee TG, Ho R, Cao B, McIntyre RS (2024) Number needed to treat (nnt) for ketamine and esketamine in adults with treatment-resistant depression: a systematic review and meta-analysis. J Affect Disord 356:753\u2013762","journal-title":"J Affect Disord"},{"key":"1865_CR62","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/j.biopsych.2015.10.018","volume":"80","author":"JB Singh","year":"2016","unstructured":"Singh JB, Fedgchin M, Daly E, Xi L, Melman C, De Bruecker G, Tadic A, Sienaert P, Wiegand F, Manji H (2016) Intravenous esketamine in adult treatment-resistant depression: a double-blind, double-randomization, placebo-controlled study. Biol Psychiatry 80:424\u2013431","journal-title":"Biol Psychiatry"},{"key":"1865_CR63","doi-asserted-by":"publisher","first-page":"2482","DOI":"10.1038\/npp.2017.94","volume":"42","author":"T-P Su","year":"2017","unstructured":"Su T-P, Chen M-H, Li C-T, Lin W-C, Hong C-J, Gueorguieva R, Tu P-C, Bai Y-M, Cheng C-M, Krystal JH (2017) Dose-related effects of adjunctive ketamine in Taiwanese patients with treatment-resistant depression. Neuropsychopharmacology 42:2482\u20132492","journal-title":"Neuropsychopharmacology"},{"key":"1865_CR64","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1038\/s41380-018-0256-5","volume":"25","author":"M Fava","year":"2020","unstructured":"Fava M, Freeman MP, Flynn M, Judge H, Hoeppner BB, Cusin C, Ionescu DF, Mathew SJ, Chang LC, Iosifescu DV (2020) Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (trd). Mol Psychiatry 25:1592\u20131603","journal-title":"Mol Psychiatry"},{"key":"1865_CR65","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ejphar.2012.11.023","volume":"698","author":"R Moaddel","year":"2013","unstructured":"Moaddel R, Abdrakhmanova G, Kozak J, Jozwiak K, Toll L, Jimenez L, Rosenberg A, Tran T, Xiao Y, Zarate CA (2013) Sub-anesthetic concentrations of (r, s)-ketamine metabolites inhibit acetylcholine-evoked currents in \u03b17 nicotinic acetylcholine receptors. Eur J Pharmacol 698:228\u2013234","journal-title":"Eur J Pharmacol"},{"key":"1865_CR66","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1001\/jamapsychiatry.2017.3739","volume":"75","author":"EJ Daly","year":"2018","unstructured":"Daly EJ, Singh JB, Fedgchin M, Cooper K, Lim P, Shelton RC, Thase ME, Winokur A, Van Nueten L, Manji H (2018) Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry 75:139\u2013148","journal-title":"JAMA Psychiatry"},{"key":"1865_CR67","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1176\/appi.focus.17105","volume":"17","author":"CM Canuso","year":"2019","unstructured":"Canuso CM, Singh JB, Fedgchin M, Alphs L, Lane R, Lim P, Pinter C, Hough D, Sanacora G, Manji H (2019) 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. FOCUS 17:55\u201365","journal-title":"FOCUS"},{"key":"1865_CR68","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1093\/ijnp\/pyz039","volume":"22","author":"M Fedgchin","year":"2019","unstructured":"Fedgchin M, Trivedi M, Daly EJ, Melkote R, Lane R, Lim P, Vitagliano D, Blier P, Fava M, Liebowitz M, Ravindran A, Gaillard R, Ameele HVD, Preskorn S, Manji H, Hough D, Drevets WC, Singh JB (2019) 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 22:616\u2013630","journal-title":"Int J Neuropsychopharmacol"},{"key":"1865_CR69","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1176\/appi.ajp.2019.19020172","volume":"176","author":"V Popova","year":"2019","unstructured":"Popova V, Daly EJ, Trivedi M, Cooper K, Lane R, Lim P, Mazzucco C, Hough D, Thase ME, Shelton RC (2019) 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 176:428\u2013438","journal-title":"Am J Psychiatry"},{"key":"1865_CR70","first-page":"17069","volume":"367","author":"E Mahase","year":"2019","unstructured":"Mahase E (2019) Esketamine is approved in Europe for treating resistant major depressive disorder. BMJ 367:17069","journal-title":"BMJ"},{"key":"1865_CR71","doi-asserted-by":"publisher","first-page":"6605","DOI":"10.4088\/JCP.19m13191","volume":"81","author":"D-J Fu","year":"2020","unstructured":"Fu D-J, Ionescu DF, Li X, Lane R, Lim P, Sanacora G, Hough D, Manji H, Drevets WC, Canuso CM (2020) Esketamine nasal spray for rapid reduction of major depressive disorder symptoms in patients who have active suicidal ideation with intent: Double-blind, randomized study (aspire i). J Clin Psychiatry 81:6605","journal-title":"J Clin Psychiatry"},{"key":"1865_CR72","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1093\/ijnp\/pyaa068","volume":"24","author":"DF Ionescu","year":"2021","unstructured":"Ionescu DF, Fu D-J, Qiu X, Lane R, Lim R, Kasper S, Hough D, Drevets WC, Manji H, Canuso CM (2021) 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 24:22\u201331","journal-title":"Int J Neuropsychopharmacol"},{"key":"1865_CR73","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1056\/NEJMoa2304145","volume":"389","author":"A Reif","year":"2023","unstructured":"Reif A, Bitter I, Buyze J, Cebulla K, Frey R, Fu D-J, Ito T, Kambarov Y, Llorca P-M, Oliveira-Maia AJ, Messer T, Mulhern-Haughey S, Rive B, von Holt C, Young AH, Godinov Y, Investigators ESCAPE-TRD (2023) Esketamine nasal spray versus quetiapine for treatment-resistant depression. N Engl J Med 389:1298\u20131309","journal-title":"N Engl J Med"},{"key":"1865_CR74","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1093\/ijnp\/pyaa027","volume":"23","author":"M Nijs","year":"2020","unstructured":"Nijs M, Wajs E, Aluisio L, Turkoz I, Daly E, Janik A, Borentain S, Singh JB, DiBernardo A, Wiegand F (2020) Managing esketamine treatment frequency toward successful outcomes: analysis of phase 3 data. Int J Neuropsychopharmacol 23:426\u2013433","journal-title":"Int J Neuropsychopharmacol"},{"key":"1865_CR75","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1038\/s41386-023-01577-5","volume":"48","author":"N Zaki","year":"2023","unstructured":"Zaki N, Chen LN, Lane R, Doherty T, Drevets WC, Morrison RL, Sanacora G, Wilkinson ST, Popova V, Fu D-J (2023) 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 48:1225\u20131233","journal-title":"Neuropsychopharmacology"},{"key":"1865_CR76","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1007\/s40263-023-01026-3","volume":"37","author":"M Castro","year":"2023","unstructured":"Castro M, Wilkinson ST, Al Jurdi RK, Petrillo MP, Zaki N, Borentain S, Fu D-J, Turkoz I, Sun L, Brown B, Cabrera P (2023) Efficacy and safety of esketamine nasal spray in patients with treatment-resistant depression who completed a second induction period: analysis of the ongoing sustain-3 study. CNS Drugs 37:715\u2013723","journal-title":"CNS Drugs"},{"key":"1865_CR77","doi-asserted-by":"publisher","first-page":"3658","DOI":"10.1038\/s41380-022-01652-1","volume":"27","author":"GC Medeiros","year":"2022","unstructured":"Medeiros GC, Gould TD, Prueitt WL, Nanavati J, Grunebaum MF, Farber NB, Singh B, Selvaraj S, Machado-Vieira R, Achtyes ED (2022) Blood-based biomarkers of antidepressant response to ketamine and esketamine: a systematic review and meta-analysis. Mol Psychiatry 27:3658\u20133669","journal-title":"Mol Psychiatry"},{"key":"1865_CR78","doi-asserted-by":"publisher","first-page":"2017","DOI":"10.1091\/mbc.e13-06-0339","volume":"25","author":"P Liu","year":"2014","unstructured":"Liu P, Choi Y-K, Qi RZ (2014) Nme7 is a functional component of the \u03b3-tubulin ring complex. Mol Biol Cell 25:2017\u20132025","journal-title":"Mol Biol Cell"},{"key":"1865_CR79","doi-asserted-by":"publisher","first-page":"12649","DOI":"10.1038\/s41598-020-69291-6","volume":"10","author":"QS Li","year":"2020","unstructured":"Li QS, Wajs E, Ochs-Ross R, Singh J, Drevets WC (2020) Genome-wide association study and polygenic risk score analysis of esketamine treatment response. Sci Rep 10:12649","journal-title":"Sci Rep"},{"key":"1865_CR80","doi-asserted-by":"publisher","first-page":"e894","DOI":"10.1038\/tp.2016.145","volume":"6","author":"D Rotroff","year":"2016","unstructured":"Rotroff D, Corum D, Motsinger-Reif A, Fiehn O, Bottrel N, Drevets W, Singh J, Salvadore G, Kaddurah-Daouk R (2016) Metabolomic signatures of drug response phenotypes for ketamine and esketamine in subjects with refractory major depressive disorder: new mechanistic insights for rapid acting antidepressants. Transl Psychiatry 6:e894\u2013e894","journal-title":"Transl Psychiatry"},{"key":"1865_CR81","doi-asserted-by":"crossref","unstructured":"Kumar R, Nu\u00f1ez NA, Joshi N, Joseph B, Verde A, Seshadri A, Cuellar Barboza AB, Prokop LJ, Medeiros GC, Singh B (2024) Metabolomic biomarkers for (r, s)-ketamine and (s)\u2010ketamine in treatment\u2010resistant depression and healthy controls: A systematic review. Bipolar Disord Feb 7 [online ahead of print]","DOI":"10.1111\/bdi.13412"},{"key":"1865_CR82","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1080\/08941939.2019.1710626","volume":"34","author":"P Liu","year":"2021","unstructured":"Liu P, Li P, Li Q, Yan H, Shi X, Liu C, Zhang Y, Peng S (2021) Effect of pretreatment of s-ketamine on postoperative depression for breast cancer patients. J Invest Surg 34:883\u2013888","journal-title":"J Invest Surg"},{"key":"1865_CR83","first-page":"e922028","volume":"26","author":"J Wang","year":"2020","unstructured":"Wang J, Wang Y, Xu X, Peng S, Xu F, Liu P (2020) Use of various doses of s-ketamine in treatment of depression and pain in cervical carcinoma patients with mild\/moderate depression after laparoscopic total hysterectomy. Med Sci Monit 26:e922028\u2013e922021","journal-title":"Med Sci Monit"},{"key":"1865_CR84","doi-asserted-by":"publisher","first-page":"111447","DOI":"10.1016\/j.jclinane.2024.111447","volume":"95","author":"T Luo","year":"2024","unstructured":"Luo T, Deng Z, Ren Q, Mu F, Zhang Y, Wang H (2024) Effects of esketamine on postoperative negative emotions and early cognitive disorders in patients undergoing non-cardiac thoracic surgery: a randomized controlled trial. J Clin Anesth 95:111447","journal-title":"J Clin Anesth"},{"key":"1865_CR85","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1186\/s12871-023-02170-5","volume":"23","author":"T Liu","year":"2023","unstructured":"Liu T, Zhang X, Li A, Liu T, Yang X, Zhang H, Lei Y, Yang Q, Dong H (2023) Effects of intra-operative administration of subanesthetic s-ketamine on emergence from sevoflurane anesthesia: a randomized double-blind placebo-controlled study. BMC Anesthesiol 23:221","journal-title":"BMC Anesthesiol"},{"key":"1865_CR86","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1080\/15622975.2021.2020900","volume":"23","author":"M G\u00e4rtner","year":"2022","unstructured":"G\u00e4rtner M, de Rover M, V\u00e1clav\u016f L, Scheidegger M, van Osch MJ, Grimm S (2022) Increase in thalamic cerebral blood flow is associated with antidepressant effects of ketamine in major depressive disorder. World J Biol Psychiatry 23:643\u2013652","journal-title":"World J Biol Psychiatry"},{"key":"1865_CR87","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1002\/hbm.24791","volume":"41","author":"N Zacharias","year":"2020","unstructured":"Zacharias N, Musso F, M\u00fcller F, Lammers F, Saleh A, London M, de Boer P, Winterer G (2020) Ketamine effects on default mode network activity and vigilance: a randomized, placebo-controlled crossover simultaneous fmri\/eeg study. Hum Brain Mapp 41:107\u2013119","journal-title":"Hum Brain Mapp"},{"key":"1865_CR88","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1038\/s41398-021-01318-6","volume":"11","author":"A H\u00f6flich","year":"2021","unstructured":"H\u00f6flich A, Kraus C, Pfeiffer RM, Seiger R, Rujescu D, Zarate CA Jr, Kasper S, Winkler D, Lanzenberger R (2021) Translating the immediate effects of s-ketamine using hippocampal subfield analysis in healthy subjects-results of a randomized controlled trial. Transl Psychiatry 11:200","journal-title":"Transl Psychiatry"},{"key":"1865_CR89","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1038\/s41398-023-02346-0","volume":"13","author":"LV Danyeli","year":"2023","unstructured":"Danyeli LV, Sen ZD, Colic L, Kurzweil L, Gensberger-Reigl S, Macharadze T, G\u00f6tting F, Refisch A, Liebe T, Chand T (2023) Association of the delayed changes in glutamate levels and functional connectivity with the immediate network effects of s-ketamine. Transl Psychiatry 13:60","journal-title":"Transl Psychiatry"},{"key":"1865_CR90","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.jpsychires.2024.02.019","volume":"172","author":"LV Danyeli","year":"2024","unstructured":"Danyeli LV, Sen ZD, Colic L, Opel N, Refisch A, Blekic N, Macharadze T, Kretzschmar M, Munk MJ, Gaser C (2024) Cortical thickness of the posterior cingulate cortex is associated with the ketamine-induced altered sense of self: an ultra-high field mri study. J Psychiatr Res 172:136\u2013143","journal-title":"J Psychiatr Res"},{"key":"1865_CR91","doi-asserted-by":"publisher","first-page":"306440","DOI":"10.3389\/fpsyt.2018.00022","volume":"9","author":"KB Bojesen","year":"2018","unstructured":"Bojesen KB, Andersen KA, Rasmussen SN, Rostrup E (2018) Glutamate levels and resting cerebral blood flow in anterior cingulate cortex are associated at rest and immediately following infusion of s-ketamine in healthy volunteers. Front Psychiatry 9:306440","journal-title":"Front Psychiatry"},{"key":"1865_CR92","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.euroneuro.2019.02.008","volume":"29","author":"M G\u00e4rtner","year":"2019","unstructured":"G\u00e4rtner M, Aust S, Bajbouj M, Fan Y, Wingenfeld K, Otte C, Heuser-Collier I, B\u00f6ker H, H\u00e4ttenschwiler J, Seifritz E (2019) Functional connectivity between prefrontal cortex and subgenual cingulate predicts antidepressant effects of ketamine. Eur Neuropsychopharmacol 29:501\u2013508","journal-title":"Eur Neuropsychopharmacol"},{"key":"1865_CR93","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.euroneuro.2020.11.017","volume":"43","author":"A Herrera-Melendez","year":"2021","unstructured":"Herrera-Melendez A, Stippl A, Aust S, Scheidegger M, Seifritz E, Heuser-Collier I, Otte C, Bajbouj M, Grimm S, G\u00e4rtner M (2021) Gray matter volume of rostral anterior cingulate cortex predicts rapid antidepressant response to ketamine. Eur Neuropsychopharmacol 43:63\u201370","journal-title":"Eur Neuropsychopharmacol"},{"key":"1865_CR94","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1093\/ijnp\/pyac049","volume":"25","author":"A Weigand","year":"2022","unstructured":"Weigand A, G\u00e4rtner M, Scheidegger M, Wyss PO, Henning A, Seifritz E, Stippl A, Herrera-Melendez A, Bajbouj M, Aust S (2022) Predicting antidepressant effects of ketamine: the role of the pregenual anterior cingulate cortex as a multimodal neuroimaging biomarker. Int J Neuropsychopharmacol 25:1003\u20131013","journal-title":"Int J Neuropsychopharmacol"},{"key":"1865_CR95","doi-asserted-by":"publisher","first-page":"499","DOI":"10.3389\/fncel.2019.00499","volume":"13","author":"K Bera","year":"2019","unstructured":"Bera K, Kamajaya A, Shivange AV, Muthusamy AK, Nichols AL, Borden PM, Grant S, Jeon J, Lin E, Bishara I (2019) Biosensors show the pharmacokinetics of s-ketamine in the endoplasmic reticulum. Front Cell Neurosci 13:499","journal-title":"Front Cell Neurosci"},{"key":"1865_CR96","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.3390\/ph16071013","volume":"16","author":"GA Alt\u00ea","year":"2023","unstructured":"Alt\u00ea GA, Rodrigues ALS (2023) Exploring the molecular targets for the antidepressant and antisuicidal effects of ketamine enantiomers by using network pharmacology and molecular docking. Pharmaceuticals (Basel) 16:1013","journal-title":"Pharmaceuticals (Basel)"},{"key":"1865_CR97","doi-asserted-by":"publisher","first-page":"549080","DOI":"10.3389\/fpsyt.2021.549080","volume":"12","author":"J Vankawala","year":"2021","unstructured":"Vankawala J, Naples G, Avila-Quintero VJ, Ramirez KL, Flores JM, Bloch MH, Dwyer JB (2021) Meta-analysis: hemodynamic responses to sub-anesthetic doses of ketamine in patients with psychiatric disorders. Front Psychiatry 12:549080","journal-title":"Front Psychiatry"},{"key":"1865_CR98","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1093\/bja\/aev135","volume":"115","author":"N Khalili-Mahani","year":"2015","unstructured":"Khalili-Mahani N, Martini C, Olofsen E, Dahan A, Niesters M (2015) Effect of subanaesthetic ketamine on plasma and saliva cortisol secretion. Br J Anaesth 115:68\u201375","journal-title":"Br J Anaesth"},{"key":"1865_CR99","doi-asserted-by":"publisher","first-page":"115168","DOI":"10.1016\/j.jpba.2022.115168","volume":"224","author":"H Toki","year":"2023","unstructured":"Toki H, Yamaguchi J-i, Mizuno-Yasuhira A, Endo H (2023) Chiral lc-ms\/ms method for the simultaneous determination of (r, s)-ketamine,(r, s)-norketamine, and (2r, 6r; 2s, 6s)-hydroxynorketamine in mouse plasma and brain. J Pharm Biomed Anal 224:115168","journal-title":"J Pharm Biomed Anal"},{"key":"1865_CR100","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1097\/ALN.0000000000003829","volume":"135","author":"M Hasan","year":"2021","unstructured":"Hasan M, Modess C, Roustom T, Dokter A, Grube M, Link A, Rey H, Adler S, Meissner K, Siegmund W (2021) Chiral pharmacokinetics and metabolite profile of prolonged-release ketamine tablets in healthy human subjects. Anesthesiology 135:326\u2013339","journal-title":"Anesthesiology"},{"key":"1865_CR101","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1093\/ijnp\/pyy041","volume":"21","author":"JR Gilbert","year":"2018","unstructured":"Gilbert JR, Yarrington JS, Wills KE, Nugent AC, Zarate CA Jr (2018) Glutamatergic signaling drives ketamine-mediated response in depression: evidence from dynamic causal modeling. Int J Neuropsychopharmacol 21:740\u2013747","journal-title":"Int J Neuropsychopharmacol"},{"key":"1865_CR102","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/s41398-021-01442-3","volume":"11","author":"ED Fagerholm","year":"2021","unstructured":"Fagerholm ED, Leech R, Williams S, Zarate CA Jr, Moran RJ, Gilbert JR (2021) Fine-tuning neural excitation\/inhibition for tailored ketamine use in treatment-resistant depression. Transl Psychiatry 11:335","journal-title":"Transl Psychiatry"},{"key":"1865_CR103","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1016\/S2215-0366(23)00183-9","volume":"10","author":"GC Medeiros","year":"2023","unstructured":"Medeiros GC, Matheson M, Demo I, Reid MJ, Matheson S, Twose C, Smith GS, Gould TD, Zarate CA, Barrett FS (2023) Brain-based correlates of antidepressant response to ketamine: a comprehensive systematic review of neuroimaging studies. Lancet Psychiatry 10:790\u2013800","journal-title":"Lancet Psychiatry"},{"key":"1865_CR104","first-page":"2","volume":"163","author":"RR Nunes","year":"2023","unstructured":"Nunes RR, Akamine FM, Meireles BR, de Moraes Nobre DG, Nascimento JCR (2023) Influence of s-ketamine, at low doses, on the electroencephalogram-bis suppression rate: a randomized clinical trial. J Surg Anesth Res 163:2\u20135","journal-title":"J Surg Anesth Res"},{"key":"1865_CR105","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1177\/0269881113512909","volume":"28","author":"J Frolich","year":"2014","unstructured":"Frolich J, Van Horn JD (2014) Reviewing the ketamine model for schizophrenia. J Psychopharmacol 28:287\u2013302","journal-title":"J Psychopharmacol"},{"key":"1865_CR106","doi-asserted-by":"publisher","first-page":"3373","DOI":"10.2147\/IJGM.S421265","volume":"16","author":"L-L Liu","year":"2023","unstructured":"Liu L-L, Hu J-H, Pan J-J, Liu H, Ji F-H, Peng K (2023) An intraoperative sub-anesthetic dose of esketamine on postoperative depressive symptoms in perimenopausal women with breast cancer undergoing modified radical mastectomy: protocol for a randomized, triple-blinded, controlled trial. Int J Gen Med 16:3373\u20133381","journal-title":"Int J Gen Med"},{"key":"1865_CR107","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1097\/JCP.0000000000000316","volume":"35","author":"MA Frye","year":"2015","unstructured":"Frye MA, Blier P, Tye SJ (2015) Concomitant benzodiazepine use attenuates ketamine response: implications for large scale study design and clinical development. J Clin Psychopharmacol 35:334\u2013336","journal-title":"J Clin Psychopharmacol"},{"key":"1865_CR108","doi-asserted-by":"publisher","first-page":"1863","DOI":"10.4088\/JCP.16l11277","volume":"78","author":"CS Albott","year":"2017","unstructured":"Albott CS, Shiroma PR, Cullen KR, Johns B, Thuras P, Wels J, Lim KO (2017) The antidepressant effect of repeat dose intravenous ketamine is delayed by concurrent benzodiazepine use. J Clin Psychiatry 78:1863","journal-title":"J Clin Psychiatry"},{"key":"1865_CR109","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1176\/appi.ajp.2017.17060647","volume":"175","author":"MF Grunebaum","year":"2018","unstructured":"Grunebaum MF, Galfalvy HC, Choo T-H, Keilp JG, Moitra VK, Parris MS, Marver JE, Burke AK, Milak MS, Sublette ME (2018) Ketamine for rapid reduction of suicidal thoughts in major depression: a midazolam-controlled randomized clinical trial. Am J Psychiatry 175:327\u2013335","journal-title":"Am J Psychiatry"},{"key":"1865_CR110","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1080\/14740338.2022.2066651","volume":"21","author":"S Nikayin","year":"2022","unstructured":"Nikayin S, Murphy E, Krystal JH, Wilkinson ST (2022) Long-term safety of ketamine and esketamine in treatment of depression. Expert Opin Drug Saf 21:777\u2013787","journal-title":"Expert Opin Drug Saf"},{"key":"1865_CR111","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1097\/HRP.0000000000000312","volume":"29","author":"B Souza-Marques","year":"2021","unstructured":"Souza-Marques B, Santos-Lima C, Araujo-de-Freitas L, Vieira F, Jesus-Nunes AP, Quarantini LC, Sampaio AS (2021) Neurocognitive effects of ketamine and esketamine for treatment-resistant major depressive disorder: a systematic review. Harv Rev Psychiatry 29:340\u2013350","journal-title":"Harv Rev Psychiatry"},{"key":"1865_CR112","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/s13034-023-00647-2","volume":"17","author":"X Lan","year":"2023","unstructured":"Lan X, Wang C, Zhang F, Liu H, Li W, Ye Y, Hu Z, Mai S, Ning Y, Zhou Y (2023) Short-term cognitive effects of repeated-dose esketamine in adolescents with major depressive disorder and suicidal ideation: a randomized controlled trial. Child Adolesc Psychiatry Ment Health 17:108","journal-title":"Child Adolesc Psychiatry Ment Health"},{"key":"1865_CR113","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1097\/PRA.0000000000000723","volume":"29","author":"M Pepe","year":"2023","unstructured":"Pepe M, Bartolucci G, Marcelli I, Simonetti A, Camardese G, Di Nicola M, Sani G (2023) Reduction in cognitive symptoms following intranasal esketamine administration in patients with chronic treatment-resistant depression: a 12-week case series. J Psychiatr Pract 29:325\u2013332","journal-title":"J Psychiatr Pract"},{"key":"1865_CR114","doi-asserted-by":"publisher","first-page":"3175","DOI":"10.1007\/s00213-017-4706-6","volume":"234","author":"AJ van de Loo","year":"2017","unstructured":"van de Loo AJ, Bervoets AC, Mooren L, Bouwmeester NH, Garssen J, Zuiker R, van Amerongen G, van Gerven J, Singh J, der Ark PV (2017) The effects of intranasal esketamine (84\u00a0mg) and oral mirtazapine (30\u00a0mg) on on-road driving performance: a double-blind, placebo-controlled study. Psychopharmacology 234:3175\u20133183","journal-title":"Psychopharmacology"},{"key":"1865_CR115","doi-asserted-by":"publisher","first-page":"1281529","DOI":"10.3389\/fdgth.2023.1281529","volume":"5","author":"TM Solomon","year":"2023","unstructured":"Solomon TM, Hajduk M, Majernik M, Jemison J, Deschamps A, Scoggins J, Kolar A, Pinheiro MA, Dubec P, Skala O (2023) Evaluating passive physiological data collection during spravato treatment. Front Digit Health 5:1281529","journal-title":"Front Digit Health"},{"key":"1865_CR116","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1111\/fcp.12745","volume":"36","author":"J Baudot","year":"2022","unstructured":"Baudot J, Soeiro T, Tambon M, Navarro N, Veyrac G, Mezaache S, Micallef J (2022) Safety concerns on the abuse potential of esketamine: multidimensional analysis of a new anti-depressive drug on the market. Fundam Clin Pharmacol 36:572\u2013581","journal-title":"Fundam Clin Pharmacol"},{"key":"1865_CR117","first-page":"487","volume-title":"Neuroinflammation, gut-brain axis and immunity in neuropsychiatric disorders advances in experimental medicine and biology","author":"A Halaris","year":"2023","unstructured":"Halaris A, Cook J (2023) The glutamatergic system in treatment-resistant depression and comparative effectiveness of ketamine and esketamien: role of inflammation? In: Kim YK (ed) Neuroinflammation, gut-brain axis and immunity in neuropsychiatric disorders advances in experimental medicine and biology. Springer, Singapore, pp 487\u2013512"}],"container-title":["European Archives of Psychiatry and Clinical Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00406-024-01865-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00406-024-01865-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00406-024-01865-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T13:03:11Z","timestamp":1759755791000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00406-024-01865-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,13]]},"references-count":117,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["1865"],"URL":"https:\/\/doi.org\/10.1007\/s00406-024-01865-1","relation":{},"ISSN":["0940-1334","1433-8491"],"issn-type":[{"value":"0940-1334","type":"print"},{"value":"1433-8491","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,13]]},"assertion":[{"value":"4 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Dr. Zarate is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; as a co-inventor on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydroxylated and hydroxylated metabolites of (R, S)-ketamine metabolites in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders. He has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. Drs. Johnston and Kvarta have no conflict of interest to disclose, financial or otherwise.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}