{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:51:32Z","timestamp":1792612292602,"version":"4.5.0"},"reference-count":110,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Johann Wolfgang Goethe-Universit\u00e4t, Frankfurt am Main"}],"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>Changes in glutamatergic neuroplasticity has been proposed as one of the core mechanisms underlying the pathophysiology of depression. In consequence components of the glutamatergic synapse have been explored as potential targets for antidepressant treatment. The rapid antidepressant effect of the NMDA receptor antagonist ketamine and subsequent approval of its S-enantiomer (i.e. esketamine), have set the precedent for investigation into other glutamatergic rapid acting antidepressants (RAADs). In this review, we discuss the potential of the different glutamatergic targets for antidepressant treatment. We describe important clinical outcomes of several key molecules targeting components of the glutamatergic synapse and their applicability as RAADs. Specifically, here we focus on substances beyond (es)ketamine, for which meaningful data from clinical trials are available, including arketamine, esmethadone, nitrous oxide and other glutamate receptor modulators. Molecules only successful in preclinical settings and case reports\/series are only marginally discussed. With this review, we aim underscore the critical role of glutamatergic modulation in advancing antidepressant therapy, thereby possibly enhancing clinical outcomes but also to reducing the burden of depression through faster therapeutic effects.<\/jats:p>","DOI":"10.1007\/s00406-024-01875-z","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T02:02:37Z","timestamp":1724896957000},"page":"1547-1557","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Advancing past ketamine: emerging glutamatergic compounds for the treatment of depression"],"prefix":"10.1007","volume":"275","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1438-3850","authenticated-orcid":false,"given":"Florian","family":"Freudenberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7628-8413","authenticated-orcid":false,"given":"Christine","family":"Reif-Leonhard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0992-634X","authenticated-orcid":false,"given":"Andreas","family":"Reif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"1875_CR1","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1126\/SCIENCE.2704997","volume":"244","author":"TJ Shors","year":"1989","unstructured":"Shors TJ, Seib TB, Levine S, Thompson RF (1989) Inescapable versus escapable shock modulates long-term potentiation in the rat hippocampus. Science 244:224\u2013226. https:\/\/doi.org\/10.1126\/SCIENCE.2704997","journal-title":"Science"},{"key":"1875_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0014-2999(90)90204-J","volume":"185","author":"R Trullas","year":"1990","unstructured":"Trullas R, Skolnick P (1990) Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. Eur J Pharmacol 185:1\u201310. https:\/\/doi.org\/10.1016\/0014-2999(90)90204-J","journal-title":"Eur J Pharmacol"},{"key":"1875_CR3","doi-asserted-by":"publisher","first-page":"385","DOI":"10.31887\/DCNS.2008.10.4\/GRACAGNI","volume":"10","author":"G Racagni","year":"2008","unstructured":"Racagni G, Popoli M (2008) Cellular and molecular mechanisms in the long-term action of antidepressants. Dialogues Clin Neurosci 10:385\u2013400. https:\/\/doi.org\/10.31887\/DCNS.2008.10.4\/GRACAGNI","journal-title":"Dialogues Clin Neurosci"},{"key":"1875_CR4","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1093\/IJNP\/PYY094","volume":"22","author":"B Kadriu","year":"2019","unstructured":"Kadriu B, Musazzi L, Henter ID et al (2019) Glutamatergic neurotransmission: pathway to developing novel rapid-acting antidepressant treatments. Int J Neuropsychopharmacol 22:119\u2013135. https:\/\/doi.org\/10.1093\/IJNP\/PYY094","journal-title":"Int J Neuropsychopharmacol"},{"key":"1875_CR5","doi-asserted-by":"publisher","first-page":"3484","DOI":"10.1007\/S12035-018-1306-3","volume":"56","author":"W Cui","year":"2019","unstructured":"Cui W, Ning Y, Hong W et al (2019) Crosstalk between inflammation and glutamate system in depression: signaling pathway and molecular biomarkers for ketamine\u2019s antidepressant effect. Mol Neurobiol 56:3484\u20133500. https:\/\/doi.org\/10.1007\/S12035-018-1306-3","journal-title":"Mol Neurobiol"},{"key":"1875_CR6","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1111\/EJN.14720","volume":"53","author":"R Troubat","year":"2021","unstructured":"Troubat R, Barone P, Leman S et al (2021) Neuroinflammation and depression: a review. Eur J Neurosci 53:151\u2013171. https:\/\/doi.org\/10.1111\/EJN.14720","journal-title":"Eur J Neurosci"},{"key":"1875_CR7","doi-asserted-by":"publisher","DOI":"10.1007\/7854_2016_40","author":"E Haroon","year":"2017","unstructured":"Haroon E, Miller AH (2017) Inflammation effects on brain glutamate in depression: mechanistic considerations and treatment implications. Curr Top Behav Neurosci. https:\/\/doi.org\/10.1007\/7854_2016_40","journal-title":"Curr Top Behav Neurosci"},{"key":"1875_CR8","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/J.NEURON.2019.03.013","volume":"102","author":"RS Duman","year":"2019","unstructured":"Duman RS, Sanacora G, Krystal JH (2019) Altered connectivity in depression: GABA and glutamate neurotransmitter deficits and reversal by novel treatments. Neuron 102:75\u201390. https:\/\/doi.org\/10.1016\/J.NEURON.2019.03.013","journal-title":"Neuron"},{"key":"1875_CR9","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.neubiorev.2015.03.005","volume":"52","author":"F Freudenberg","year":"2015","unstructured":"Freudenberg F, Celikel T, Reif A (2015) The role of \u03b1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in depression: central mediators of pathophysiology and antidepressant activity? Neurosci Biobehav Rev 52:193\u2013206. https:\/\/doi.org\/10.1016\/j.neubiorev.2015.03.005","journal-title":"Neurosci Biobehav Rev"},{"key":"1875_CR10","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1016\/J.BIOPSYCH.2012.11.009","volume":"73","author":"L Musazzi","year":"2013","unstructured":"Musazzi L, Treccani G, Mallei A, Popoli M (2013) The action of antidepressants on the glutamate system: regulation of glutamate release and glutamate receptors. Biol Psychiatry 73:1180\u20131188. https:\/\/doi.org\/10.1016\/J.BIOPSYCH.2012.11.009","journal-title":"Biol Psychiatry"},{"key":"1875_CR11","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/S41583-021-00540-X","volume":"23","author":"G Sanacora","year":"2022","unstructured":"Sanacora G, Yan Z, Popoli M (2022) The stressed synapse 2.0: pathophysiological mechanisms in stress-related neuropsychiatric disorders. Nat Rev Neurosci 23:86\u2013103. https:\/\/doi.org\/10.1038\/S41583-021-00540-X","journal-title":"Nat Rev Neurosci"},{"key":"1875_CR12","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/S41386-023-01629-W","volume":"49","author":"JH Krystal","year":"2024","unstructured":"Krystal JH, Kavalali ET, Monteggia LM (2024) Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms. Neuropsychopharmacology 49:41\u201350. https:\/\/doi.org\/10.1038\/S41386-023-01629-W","journal-title":"Neuropsychopharmacology"},{"key":"1875_CR13","doi-asserted-by":"publisher","DOI":"10.1073\/PNAS.2305772120","author":"JH Krystal","year":"2023","unstructured":"Krystal JH, Kaye AP, Jefferson S et al (2023) Ketamine and the neurobiology of depression: toward next-generation rapid-acting antidepressant treatments. Proc Natl Acad Sci U S A. https:\/\/doi.org\/10.1073\/PNAS.2305772120","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1875_CR14","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/J.PHARMTHERA.2018.05.010","volume":"190","author":"CG Abdallah","year":"2018","unstructured":"Abdallah CG, Sanacora G, Duman RS, Krystal JH (2018) The neurobiology of depression, ketamine and rapid-acting antidepressants: is it glutamate inhibition or activation? Pharmacol Ther 190:148\u2013158. https:\/\/doi.org\/10.1016\/J.PHARMTHERA.2018.05.010","journal-title":"Pharmacol Ther"},{"key":"1875_CR15","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1038\/S41380-018-0252-9","volume":"24","author":"S Moriguchi","year":"2019","unstructured":"Moriguchi S, Takamiya A, Noda Y et al (2019) Glutamatergic neurometabolite levels in major depressive disorder: a systematic review and meta-analysis of proton magnetic resonance spectroscopy studies. Mol Psychiatry 24:952\u2013964. https:\/\/doi.org\/10.1038\/S41380-018-0252-9","journal-title":"Mol Psychiatry"},{"key":"1875_CR16","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1016\/J.PBB.2011.04.016","volume":"100","author":"K Tokita","year":"2012","unstructured":"Tokita K, Yamaji T, Hashimoto K (2012) Roles of glutamate signaling in preclinical and\/or mechanistic models of depression. Pharmacol Biochem Behav 100:688\u2013704. https:\/\/doi.org\/10.1016\/J.PBB.2011.04.016","journal-title":"Pharmacol Biochem Behav"},{"key":"1875_CR17","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/S0361-9230(01)00523-8","volume":"55","author":"JH Meador-Woodruff","year":"2001","unstructured":"Meador-Woodruff JH, Hogg AJ, Smith RE (2001) Striatal ionotropic glutamate receptor expression in schizophrenia, bipolar disorder, and major depressive disorder. Brain Res Bull 55:631\u2013640. https:\/\/doi.org\/10.1016\/S0361-9230(01)00523-8","journal-title":"Brain Res Bull"},{"key":"1875_CR18","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1017\/S1461145712000016","volume":"16","author":"V Duric","year":"2013","unstructured":"Duric V, Banasr M, Stockmeier CA et al (2013) Altered expression of synapse and glutamate related genes in post-mortem hippocampus of depressed subjects. Int J Neuropsychopharmacol 16:69\u201382. https:\/\/doi.org\/10.1017\/S1461145712000016","journal-title":"Int J Neuropsychopharmacol"},{"key":"1875_CR19","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/J.PNPBP.2008.10.005","volume":"33","author":"AM Feyissa","year":"2009","unstructured":"Feyissa AM, Chandran A, Stockmeier CA, Karolewicz B (2009) Reduced levels of NR2A and NR2B subunits of NMDA receptor and PSD-95 in the prefrontal cortex in major depression. Prog Neuropsychopharmacol Biol Psychiatry 33:70\u201375. https:\/\/doi.org\/10.1016\/J.PNPBP.2008.10.005","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"issue":"9","key":"1875_CR20","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1038\/sj.npp.1301312","volume":"32","author":"M Beneyto","year":"2007","unstructured":"Beneyto M, Kristiansen LV, Oni-Orisan A et al (2007) Abnormal glutamate receptor expression in the medial temporal lobe in schizophrenia and mood disorders. Neuropsychopharmacology 32(9):1888\u20131902. https:\/\/doi.org\/10.1038\/sj.npp.1301312","journal-title":"Neuropsychopharmacology"},{"key":"1875_CR21","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1038\/MP.2015.91","volume":"20","author":"AL Gray","year":"2015","unstructured":"Gray AL, Hyde TM, Deep-Soboslay A et al (2015) Sex differences in glutamate receptor gene expression in major depression and suicide. Mol Psychiatry 20:1057\u20131068. https:\/\/doi.org\/10.1038\/MP.2015.91","journal-title":"Mol Psychiatry"},{"key":"1875_CR22","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/s41593-018-0326-7","volume":"22","author":"DM Howard","year":"2019","unstructured":"Howard DM, Adams MJ, Clarke T et al (2019) Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nat Neurosci 22:343\u2013352. https:\/\/doi.org\/10.1038\/s41593-018-0326-7","journal-title":"Nat Neurosci"},{"key":"1875_CR23","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.neuropharm.2011.07.036","volume":"62","author":"G Sanacora","year":"2012","unstructured":"Sanacora G, Treccani G, Popoli M (2012) Towards a glutamate hypothesis of depression: an emerging frontier of neuropsychopharmacology for mood disorders. Neuropharmacology 62:63\u201377. https:\/\/doi.org\/10.1016\/j.neuropharm.2011.07.036","journal-title":"Neuropharmacology"},{"key":"1875_CR24","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/sj.npp.1301574","volume":"33","author":"C Pittenger","year":"2008","unstructured":"Pittenger C, Duman RS (2008) Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology 33:88\u2013109. https:\/\/doi.org\/10.1038\/sj.npp.1301574","journal-title":"Neuropsychopharmacology"},{"key":"1875_CR25","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 et al (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 47:351\u2013354. https:\/\/doi.org\/10.1016\/S0006-3223(99)00230-9","journal-title":"Biol Psychiatry"},{"key":"1875_CR26","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1001\/archpsyc.63.8.856","volume":"63","author":"CA Zarate","year":"2006","unstructured":"Zarate CA, Singh JB, Carlson PJ et al (2006) A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63:856. https:\/\/doi.org\/10.1001\/archpsyc.63.8.856","journal-title":"Arch Gen Psychiatry"},{"key":"1875_CR27","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. https:\/\/doi.org\/10.1038\/MP.2017.255","journal-title":"Mol Psychiatry"},{"key":"1875_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/J.PHARMTHERA.2023.108431","author":"JN Johnston","year":"2023","unstructured":"Johnston JN, Henter ID, Zarate CA (2023) The antidepressant actions of ketamine and its enantiomers. Pharmacol Ther. https:\/\/doi.org\/10.1016\/J.PHARMTHERA.2023.108431","journal-title":"Pharmacol Ther"},{"key":"1875_CR29","first-page":"8272","volume":"61","author":"RMA Hirschfeld","year":"2000","unstructured":"Hirschfeld RMA (2000) History and evolution of the monoamine hypothesis of depression. J Clin Psychiatry 61:8272","journal-title":"J Clin Psychiatry"},{"key":"1875_CR30","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.2174\/138161209788168001","volume":"15","author":"F Lopez-Munoz","year":"2009","unstructured":"Lopez-Munoz F, Alamo C (2009) Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today. Curr Pharm Des 15:1563\u20131586. https:\/\/doi.org\/10.2174\/138161209788168001","journal-title":"Curr Pharm Des"},{"key":"1875_CR31","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1002\/WPS.21120","volume":"22","author":"RS McIntyre","year":"2023","unstructured":"McIntyre RS, Alsuwaidan M, Baune BT et al (2023) Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventions. World Psychiatry 22:394\u2013412. https:\/\/doi.org\/10.1002\/WPS.21120","journal-title":"World Psychiatry"},{"key":"1875_CR32","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/J.JPSYCHIRES.2017.07.003","volume":"94","author":"S Wagner","year":"2017","unstructured":"Wagner S, Engel A, Engelmann J et al (2017) Early improvement as a resilience signal predicting later remission to antidepressant treatment in patients with major depressive disorder: systematic review and meta-analysis. J Psychiatr Res 94:96\u2013106. https:\/\/doi.org\/10.1016\/J.JPSYCHIRES.2017.07.003","journal-title":"J Psychiatr Res"},{"key":"1875_CR33","doi-asserted-by":"publisher","first-page":"344","DOI":"10.4088\/JCP.07M03780","volume":"70","author":"A Szegedi","year":"2009","unstructured":"Szegedi A, Jansen WT, Van Willigenburg APP et al (2009) Early improvement in the first 2 weeks as a predictor of treatment outcome in patients with major depressive disorder: a meta-analysis including 6562 patients. J Clin Psychiatry 70:344\u2013353. https:\/\/doi.org\/10.4088\/JCP.07M03780","journal-title":"J Clin Psychiatry"},{"key":"1875_CR34","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1159\/000518098","volume":"7","author":"L Ramos-Da-Silva","year":"2021","unstructured":"Ramos-Da-Silva L, Carlson PT, Silva-Costa LC et al (2021) Molecular mechanisms associated with antidepressant treatment on major depression. Complex Psychiatry 7:49\u201359. https:\/\/doi.org\/10.1159\/000518098","journal-title":"Complex Psychiatry"},{"key":"1875_CR35","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/J.NEUROPHARM.2015.10.034","volume":"102","author":"C Bj\u00f6rkholm","year":"2016","unstructured":"Bj\u00f6rkholm C, Monteggia LM (2016) BDNF \u2014 a key transducer of antidepressant effects. Neuropharmacology 102:72. https:\/\/doi.org\/10.1016\/J.NEUROPHARM.2015.10.034","journal-title":"Neuropharmacology"},{"issue":"8","key":"1875_CR36","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1038\/mp.2017.61","volume":"22","author":"E Castr\u00e9n","year":"2017","unstructured":"Castr\u00e9n E, Antila H (2017) Neuronal plasticity and neurotrophic factors in drug responses. Mol Psychiatry 22(8):1085\u20131095. https:\/\/doi.org\/10.1038\/mp.2017.61","journal-title":"Mol Psychiatry"},{"key":"1875_CR37","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/BS.APHA.2019.03.002","volume":"86","author":"JM Witkin","year":"2019","unstructured":"Witkin JM, Martin AE, Golani LK et al (2019) Rapid-acting antidepressants. Adv Pharmacol 86:47\u201396. https:\/\/doi.org\/10.1016\/BS.APHA.2019.03.002","journal-title":"Adv Pharmacol"},{"key":"1875_CR38","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/S2215-0366(20)30516-2","volume":"8","author":"RH McAllister-Williams","year":"2021","unstructured":"McAllister-Williams RH, Arango C, Blier P et al (2021) Reconceptualising treatment-resistant depression as difficult-to-treat depression. Lancet Psychiatry 8:14\u201315. https:\/\/doi.org\/10.1016\/S2215-0366(20)30516-2","journal-title":"Lancet Psychiatry"},{"key":"1875_CR39","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1017\/S0033291715002159","volume":"46","author":"YD Hu","year":"2016","unstructured":"Hu YD, Xiang YT, Fang JX et al (2016) Single i.v. ketamine augmentation of newly initiated escitalopram for major depression: results from a randomized, placebo-controlled 4-week study. Psychol Med 46:623\u2013635. https:\/\/doi.org\/10.1017\/S0033291715002159","journal-title":"Psychol Med"},{"key":"1875_CR40","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/J.JAD.2018.02.056","volume":"235","author":"S Arabzadeh","year":"2018","unstructured":"Arabzadeh S, Hakkikazazi E, Shahmansouri N et al (2018) Does oral administration of ketamine accelerate response to treatment in major depressive disorder? Results of a double-blind controlled trial. J Affect Disord 235:236\u2013241. https:\/\/doi.org\/10.1016\/J.JAD.2018.02.056","journal-title":"J Affect Disord"},{"key":"1875_CR41","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 et al (2023) Esketamine nasal spray versus quetiapine for treatment-resistant depression. N Engl J Med 389:1298\u20131309. https:\/\/doi.org\/10.1056\/NEJMOA2304145","journal-title":"N Engl J Med"},{"key":"1875_CR42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41398-020-00897-0","volume":"10","author":"PR Shiroma","year":"2020","unstructured":"Shiroma PR, Thuras P, Wels J et al (2020) A randomized, double-blind, active placebo-controlled study of efficacy, safety, and durability of repeated vs single subanesthetic ketamine for treatment-resistant depression. Transl Psychiatry 10:1\u20139. https:\/\/doi.org\/10.1038\/s41398-020-00897-0","journal-title":"Transl Psychiatry"},{"key":"1875_CR43","doi-asserted-by":"publisher","first-page":"2556","DOI":"10.2174\/1381612824666180730104707","volume":"24","author":"JM Witkin","year":"2018","unstructured":"Witkin JM, Knutson DE, Rodriguez GJ, Shi S (2018) Rapid-acting antidepressants. Curr Pharm Des 24:2556\u20132563. https:\/\/doi.org\/10.2174\/1381612824666180730104707","journal-title":"Curr Pharm Des"},{"key":"1875_CR44","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1126\/SCIENCE.1190287","volume":"329","author":"N Li","year":"2010","unstructured":"Li N, Lee B, Liu RJ et al (2010) mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329:959\u2013964. https:\/\/doi.org\/10.1126\/SCIENCE.1190287","journal-title":"Science"},{"key":"1875_CR45","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1038\/nm.4050","volume":"22","author":"RS Duman","year":"2016","unstructured":"Duman RS, Aghajanian GK, Sanacora G, Krystal JH (2016) Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nat Med 22:238\u2013249. https:\/\/doi.org\/10.1038\/nm.4050","journal-title":"Nat Med"},{"key":"1875_CR46","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1176\/APPI.AJP.163.1.153","volume":"163","author":"CA Zarate","year":"2006","unstructured":"Zarate CA, Singh JB, Quiroz JA et al (2006) A double-blind, placebo-controlled study of memantine in the treatment of major depression. Am J Psychiatry 163:153\u2013155. https:\/\/doi.org\/10.1176\/APPI.AJP.163.1.153","journal-title":"Am J Psychiatry"},{"key":"1875_CR47","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/NATURE17998","volume":"533","author":"P Zanos","year":"2016","unstructured":"Zanos P, Moaddel R, Morris PJ et al (2016) NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature 533:481\u2013486. https:\/\/doi.org\/10.1038\/NATURE17998","journal-title":"Nature"},{"key":"1875_CR48","doi-asserted-by":"publisher","DOI":"10.1016\/J.COPH.2014.11.006","author":"JW Johnson","year":"2015","unstructured":"Johnson JW, Glasgow NG, Povysheva NV (2015) Recent insights into the mode of action of memantine and ketamine. Curr Opin Pharmacol. https:\/\/doi.org\/10.1016\/J.COPH.2014.11.006","journal-title":"Curr Opin Pharmacol"},{"key":"1875_CR49","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1007\/S00213-023-06324-8","volume":"240","author":"DS Mathai","year":"2023","unstructured":"Mathai DS, Nayak SM, Yaden DB, Garcia-Romeu A (2023) Reconsidering \u201cdissociation\u201d as a predictor of antidepressant efficacy for esketamine. Psychopharmacology 240:827\u2013836. https:\/\/doi.org\/10.1007\/S00213-023-06324-8","journal-title":"Psychopharmacology"},{"key":"1875_CR50","doi-asserted-by":"publisher","DOI":"10.47626\/2237-6089-2022-0593","author":"MVF Echegaray","year":"2023","unstructured":"Echegaray MVF, Mello RP, Magnavita GM et al (2023) Does the intensity of dissociation predict antidepressant effects 24 hours after infusion of racemic ketamine and esketamine in treatment-resistant depression? A secondary analysis from a randomized controlled trial. Trends Psychiatry Psychother. https:\/\/doi.org\/10.47626\/2237-6089-2022-0593","journal-title":"Trends Psychiatry Psychother"},{"key":"1875_CR51","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1093\/IJNP\/PYAB084","volume":"25","author":"G Chen","year":"2022","unstructured":"Chen G, Chen L, Zhang Y et al (2022) Relationship between dissociation and antidepressant effects of esketamine nasal spray in patients with treatment-resistant depression. Int J Neuropsychopharmacol 25:269\u2013279. https:\/\/doi.org\/10.1093\/IJNP\/PYAB084","journal-title":"Int J Neuropsychopharmacol"},{"key":"1875_CR52","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEUROPHARM.2022.109219","author":"ZJ Chun","year":"2022","unstructured":"Chun ZJ, Yao W, Hashimoto K (2022) Arketamine, a new rapid-acting antidepressant: a historical review and future directions. Neuropharmacology. https:\/\/doi.org\/10.1016\/J.NEUROPHARM.2022.109219","journal-title":"Neuropharmacology"},{"key":"1875_CR53","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1007\/S00406-020-01110-5","volume":"271","author":"GC Leal","year":"2021","unstructured":"Leal GC, Bandeira ID, Correia-Melo FS et al (2021) Intravenous arketamine for treatment-resistant depression: open-label pilot study. Eur Arch Psychiatry Clin Neurosci 271:577\u2013582. https:\/\/doi.org\/10.1007\/S00406-020-01110-5","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"1875_CR54","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 et al (2023) Arketamine as adjunctive therapy for treatment-resistant depression: a placebo-controlled pilot study. J Affect Disord 330:7\u201315. https:\/\/doi.org\/10.1016\/J.JAD.2023.02.151","journal-title":"J Affect Disord"},{"key":"1875_CR55","doi-asserted-by":"publisher","first-page":"5160","DOI":"10.1073\/PNAS.1816071116","volume":"116","author":"EW Lumsden","year":"2019","unstructured":"Lumsden EW, Troppoli TA, Myers SJ et al (2019) Antidepressant-relevant concentrations of the ketamine metabolite (2 R,6 R)-hydroxynorketamine do not block NMDA receptor function. Proc Natl Acad Sci U S A 116:5160\u20135169. https:\/\/doi.org\/10.1073\/PNAS.1816071116","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1875_CR56","doi-asserted-by":"publisher","first-page":"e3","DOI":"10.1016\/J.BIOPSYCH.2017.10.020","volume":"84","author":"TH Pham","year":"2018","unstructured":"Pham TH, Defaix C, Xu X et al (2018) Common neurotransmission recruited in (R, S)-Ketamine and (2R,6R)-hydroxynorketamine-induced sustained antidepressant-like effects. Biol Psychiatry 84:e3\u2013e6. https:\/\/doi.org\/10.1016\/J.BIOPSYCH.2017.10.020","journal-title":"Biol Psychiatry"},{"key":"1875_CR57","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1073\/PNAS.1814709116","volume":"116","author":"K Fukumoto","year":"2019","unstructured":"Fukumoto K, Fogaca MV, Liu RJ et al (2019) Activity-dependent brain-derived neurotrophic factor signaling is required for the antidepressant actions of (2 R,6 R)-hydroxynorketamine. Proc Natl Acad Sci U S A 116:297\u2013302. https:\/\/doi.org\/10.1073\/PNAS.1814709116","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1875_CR58","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/J.JPSYCHIRES.2019.08.005","volume":"117","author":"MF Grunebaum","year":"2019","unstructured":"Grunebaum MF, Galfalvy HC, Choo TH et al (2019) Ketamine metabolite pilot study in a suicidal depression trial. J Psychiatr Res 117:129\u2013134. https:\/\/doi.org\/10.1016\/J.JPSYCHIRES.2019.08.005","journal-title":"J Psychiatr Res"},{"key":"1875_CR59","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1038\/s41386-020-0663-6","volume":"45","author":"CA Farmer","year":"2020","unstructured":"Farmer CA, Gilbert JR, Moaddel R et al (2020) Ketamine metabolites, clinical response, and gamma power in a randomized, placebo-controlled, crossover trial for treatment-resistant major depression. Neuropsychopharmacology 45:1398\u20131404. https:\/\/doi.org\/10.1038\/s41386-020-0663-6","journal-title":"Neuropsychopharmacology"},{"key":"1875_CR60","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1080\/14728214.2021.1898588","volume":"26","author":"A Majeed","year":"2021","unstructured":"Majeed A, Xiong J, Teopiz KM et al (2021) Efficacy of dextromethorphan for the treatment of depression: a systematic review of preclinical and clinical trials. Expert Opin Emerg Drugs 26:63\u201374. https:\/\/doi.org\/10.1080\/14728214.2021.1898588","journal-title":"Expert Opin Emerg Drugs"},{"key":"1875_CR61","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/J.JAD.2017.04.072","volume":"218","author":"JW Murrough","year":"2017","unstructured":"Murrough JW, Wade E, Sayed S et al (2017) Dextromethorphan\/quinidine pharmacotherapy in patients with treatment resistant depression: a proof of concept clinical trial. J Affect Disord 218:277\u2013283. https:\/\/doi.org\/10.1016\/J.JAD.2017.04.072","journal-title":"J Affect Disord"},{"key":"1875_CR62","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1176\/APPI.AJP.21080800","volume":"179","author":"H Tabuteau","year":"2022","unstructured":"Tabuteau H, Jones A, Anderson A et al (2022) Effect of AXS-05 (dextromethorphan-bupropion) in major depressive disorder: a randomized double-blind controlled trial. Am J Psychiatry 179:490\u2013499. https:\/\/doi.org\/10.1176\/APPI.AJP.21080800","journal-title":"Am J Psychiatry"},{"key":"1875_CR63","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.21M14345","author":"DV Iosifescu","year":"2022","unstructured":"Iosifescu DV, Jones A, O\u2019Gorman C et al (2022) Efficacy and safety of AXS-05 (dextromethorphan-bupropion) in patients with major depressive disorder: a phase 3 randomized clinical trial (GEMINI). J Clin Psychiatry. https:\/\/doi.org\/10.4088\/JCP.21M14345","journal-title":"J Clin Psychiatry"},{"key":"1875_CR64","unstructured":"Committee for Human Medicinal Products (CHMP) (2017) Guideline on clinical development of fixed combination medicinal products"},{"key":"1875_CR65","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/S43441-019-00057-7\/METRICS","volume":"54","author":"OJ Bjerrum","year":"2020","unstructured":"Bjerrum OJ, Eichendorff S, Alkis NB (2020) Analysis of the authorized target populations for fixed dose combination products between 2000 and 2017 reveals discrepancies between EMA\u2019s and FDA\u2019s views on initial dual-therapy. Ther Innov Regul Sci 54:297\u2013302. https:\/\/doi.org\/10.1007\/S43441-019-00057-7\/METRICS","journal-title":"Ther Innov Regul Sci"},{"key":"1875_CR66","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1007\/S40263-021-00816-X","volume":"35","author":"ID Henter","year":"2021","unstructured":"Henter ID, Park LT, Zarate CA (2021) Novel glutamatergic modulators for the treatment of mood disorders: current status. CNS Drugs 35:527\u2013543. https:\/\/doi.org\/10.1007\/S40263-021-00816-X","journal-title":"CNS Drugs"},{"key":"1875_CR67","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1007\/S00406-023-01571-4","volume":"273","author":"M Fava","year":"2023","unstructured":"Fava M, Stahl SM, De Martin S et al (2023) Esmethadone-HCl (REL-1017): a promising rapid antidepressant. Eur Arch Psychiatry Clin Neurosci 273:1463\u20131476. https:\/\/doi.org\/10.1007\/S00406-023-01571-4","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"1875_CR68","doi-asserted-by":"publisher","DOI":"10.3389\/FPHAR.2021.671859\/PDF","author":"S De Martin","year":"2021","unstructured":"De Martin S, Gabbia D, Folli F et al (2021) REL-1017 (esmethadone) increases circulating BDNF levels in healthy subjects of a phase 1 clinical study. Front Pharmacol. https:\/\/doi.org\/10.3389\/FPHAR.2021.671859\/PDF","journal-title":"Front Pharmacol"},{"key":"1875_CR69","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1176\/APPI.AJP.2021.21020197","volume":"179","author":"F Maurizio","year":"2022","unstructured":"Maurizio F, Stahl S, Pani L et al (2022) REL-1017 (esmethadone) as adjunctive treatment in patients with major depressive disorder: a phase 2a randomized double-blind trial. Am J Psychiatry 179:122\u2013131. https:\/\/doi.org\/10.1176\/APPI.AJP.2021.21020197","journal-title":"Am J Psychiatry"},{"key":"1875_CR70","doi-asserted-by":"publisher","DOI":"10.1136\/BMJ.O2297","author":"H Sumnall","year":"2022","unstructured":"Sumnall H (2022) Recreational use of nitrous oxide. BMJ. https:\/\/doi.org\/10.1136\/BMJ.O2297","journal-title":"BMJ"},{"key":"1875_CR71","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1093\/BMB\/LDX050","volume":"125","author":"V Lew","year":"2018","unstructured":"Lew V, McKay E, Maze M (2018) Past, present, and future of nitrous oxide. Br Med Bull 125:103\u2013119. https:\/\/doi.org\/10.1093\/BMB\/LDX050","journal-title":"Br Med Bull"},{"key":"1875_CR72","doi-asserted-by":"publisher","DOI":"10.1007\/S00406-024-01801-3","author":"G Kronenberg","year":"2024","unstructured":"Kronenberg G, Schoretsanitis G, Seifritz E, Olbrich S (2024) The boon and bane of nitrous oxide. Eur Arch Psychiatry Clin Neurosci. https:\/\/doi.org\/10.1007\/S00406-024-01801-3","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"1875_CR73","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/J.BIOPSYCH.2014.11.016","volume":"78","author":"P Nagele","year":"2015","unstructured":"Nagele P, Duma A, Kopec M et al (2015) Nitrous oxide for treatment-resistant major depression: a proof-of-concept trial. Biol Psychiatry 78:10\u201318. https:\/\/doi.org\/10.1016\/J.BIOPSYCH.2014.11.016","journal-title":"Biol Psychiatry"},{"key":"1875_CR74","doi-asserted-by":"publisher","DOI":"10.1126\/SCITRANSLMED.ABE1376","author":"P Nagele","year":"2021","unstructured":"Nagele P, Palanca BJ, Gott B et al (2021) A phase 2 trial of inhaled nitrous oxide for treatment-resistant major depression. Sci Transl Med. https:\/\/doi.org\/10.1126\/SCITRANSLMED.ABE1376","journal-title":"Sci Transl Med"},{"key":"1875_CR75","doi-asserted-by":"publisher","DOI":"10.1016\/J.PSYCHRES.2022.114867","volume":"317","author":"D Yan","year":"2022","unstructured":"Yan D, Liu B, Wei X et al (2022) Efficacy and safety of nitrous oxide for patients with treatment-resistant depression, a randomized controlled trial. Psychiatry Res 317:114867. https:\/\/doi.org\/10.1016\/J.PSYCHRES.2022.114867","journal-title":"Psychiatry Res"},{"key":"1875_CR76","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1111\/bdi.13288","volume":"25","author":"WSH Kim","year":"2023","unstructured":"Kim WSH, Dimick MK, Omrin D et al (2023) Proof-of-concept randomized controlled trial of single-session nitrous oxide treatment for refractory bipolar depression: focus on cerebrovascular target engagement. Bipolar Disord 25:221\u2013232. https:\/\/doi.org\/10.1111\/bdi.13288","journal-title":"Bipolar Disord"},{"key":"1875_CR77","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1590\/1516-4446-2020-1543","volume":"43","author":"MC Guimar\u00e3es","year":"2021","unstructured":"Guimar\u00e3es MC, Guimar\u00e3es TM, Hallak JE et al (2021) Nitrous oxide as an adjunctive therapy in major depressive disorder: a randomized controlled double-blind pilot trial. Braz J Psychiatry 43:484. https:\/\/doi.org\/10.1590\/1516-4446-2020-1543","journal-title":"Braz J Psychiatry"},{"key":"1875_CR78","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1111\/ACPS.13432","volume":"146","author":"H Liu","year":"2022","unstructured":"Liu H, Kerzner J, Demchenko I et al (2022) Nitrous oxide for the treatment of psychiatric disorders: a systematic review of the clinical trial landscape. Acta Psychiatr Scand 146:126\u2013138. https:\/\/doi.org\/10.1111\/ACPS.13432","journal-title":"Acta Psychiatr Scand"},{"key":"1875_CR79","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/IJNP\/PYV102","volume":"19","author":"S Schade","year":"2016","unstructured":"Schade S, Paulus W (2016) D-cycloserine in neuropsychiatric diseases: a systematic review. Int J Neuropsychopharmacol 19:1\u20137. https:\/\/doi.org\/10.1093\/IJNP\/PYV102","journal-title":"Int J Neuropsychopharmacol"},{"key":"1875_CR80","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1017\/S1461145712000910","volume":"16","author":"U Heresco-Levy","year":"2013","unstructured":"Heresco-Levy U, Gelfin G, Bloch B et al (2013) A randomized add-on trial of high-dose D-cycloserine for treatment-resistant depression. Int J Neuropsychopharmacol 16:501\u2013506. https:\/\/doi.org\/10.1017\/S1461145712000910","journal-title":"Int J Neuropsychopharmacol"},{"key":"1875_CR81","doi-asserted-by":"publisher","DOI":"10.1186\/s40345-023-00308-5","author":"A Nierenberg","year":"2023","unstructured":"Nierenberg A, Lavin P, Javitt DC et al (2023) NRX-101 (D-cycloserine plus lurasidone) vs. lurasidone for the maintenance of initial stabilization after ketamine in patients with severe bipolar depression with acute suicidal ideation and behavior: a randomized prospective phase 2 trial. Int J Bipolar Disord. https:\/\/doi.org\/10.1186\/s40345-023-00308-5","journal-title":"Int J Bipolar Disord"},{"key":"1875_CR82","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/J.BIOPSYCH.2012.10.019","volume":"74","author":"CA Zarate","year":"2013","unstructured":"Zarate CA, Mathews D, Ibrahim L et al (2013) A randomized trial of a low-trapping nonselective N-methyl-D-aspartate channel blocker in major depression. Biol Psychiatry 74:257\u2013264. https:\/\/doi.org\/10.1016\/J.BIOPSYCH.2012.10.019","journal-title":"Biol Psychiatry"},{"key":"1875_CR83","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1097\/JCP.0B013E31818A6CEA","volume":"28","author":"SH Preskorn","year":"2008","unstructured":"Preskorn SH, Baker B, Kolluri S et al (2008) An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder. J Clin Psychopharmacol 28:631\u2013637. https:\/\/doi.org\/10.1097\/JCP.0B013E31818A6CEA","journal-title":"J Clin Psychopharmacol"},{"key":"1875_CR84","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/J.DRUDIS.2018.11.007","volume":"24","author":"ST Wilkinson","year":"2019","unstructured":"Wilkinson ST, Sanacora G (2019) A new generation of antidepressants: an update on the pharmaceutical pipeline for novel and rapid-acting therapeutics in mood disorders based on glutamate\/GABA neurotransmitter systems. Drug Discov Today 24:606\u2013615. https:\/\/doi.org\/10.1016\/J.DRUDIS.2018.11.007","journal-title":"Drug Discov Today"},{"key":"1875_CR85","doi-asserted-by":"publisher","first-page":"2236","DOI":"10.1111\/CTS.13623","volume":"16","author":"B Gomez-Mancilla","year":"2023","unstructured":"Gomez-Mancilla B, Levy JA, Ganesan S et al (2023) MIJ821 (onfasprodil) in healthy volunteers: first-in-human, randomized, placebo-controlled study (single ascending dose and repeated intravenous dose). Clin Transl Sci 16:2236\u20132252. https:\/\/doi.org\/10.1111\/CTS.13623","journal-title":"Clin Transl Sci"},{"key":"1875_CR86","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1093\/IJNP\/PYAA025","volume":"23","author":"LT Park","year":"2020","unstructured":"Park LT, Kadriu B, Gould TD et al (2020) A randomized trial of the N-Methyl-d-aspartate receptor glycine site antagonist prodrug 4-chlorokynurenine in treatment-resistant depression. Int J Neuropsychopharmacol 23:417\u2013425. https:\/\/doi.org\/10.1093\/IJNP\/PYAA025","journal-title":"Int J Neuropsychopharmacol"},{"key":"1875_CR87","doi-asserted-by":"publisher","first-page":"5097","DOI":"10.1038\/s41380-020-0796-3","volume":"26","author":"S Pothula","year":"2020","unstructured":"Pothula S, Kato T, Liu RJ et al (2020) Cell-type specific modulation of NMDA receptors triggers antidepressant actions. Mol Psychiatry 26:5097\u20135111. https:\/\/doi.org\/10.1038\/s41380-020-0796-3","journal-title":"Mol Psychiatry"},{"key":"1875_CR88","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1097\/01.PRA.0000462606.17725.93","volume":"21","author":"S Preskorn","year":"2015","unstructured":"Preskorn S, Macaluso M, Mehra V et al (2015) Randomized proof of concept trial of GLYX-13, an N-methyl-D-aspartate receptor glycine site partial agonist, in major depressive disorder nonresponsive to a previous antidepressant agent. J Psychiatr Pract 21:140\u2013149. https:\/\/doi.org\/10.1097\/01.PRA.0000462606.17725.93","journal-title":"J Psychiatr Pract"},{"key":"1875_CR89","doi-asserted-by":"publisher","DOI":"10.1016\/J.PBB.2019.172827","author":"T Kato","year":"2020","unstructured":"Kato T, Duman RS (2020) Rapastinel, a novel glutamatergic agent with ketamine-like antidepressant actions: convergent mechanisms. Pharmacol Biochem Behav. https:\/\/doi.org\/10.1016\/J.PBB.2019.172827","journal-title":"Pharmacol Biochem Behav"},{"key":"1875_CR90","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1146\/annurev.pharmtox.011008.145533","volume":"50","author":"CM Niswender","year":"2010","unstructured":"Niswender CM, Conn PJ (2010) Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 50:295\u2013322. https:\/\/doi.org\/10.1146\/annurev.pharmtox.011008.145533","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"1875_CR91","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1007\/S00406-023-01561-6","volume":"273","author":"S Chaki","year":"2023","unstructured":"Chaki S, Watanabe M (2023) mGlu2\/3 receptor antagonists for depression: overview of underlying mechanisms and clinical development. Eur Arch Psychiatry Clin Neurosci 273:1451\u20131462. https:\/\/doi.org\/10.1007\/S00406-023-01561-6","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"1875_CR92","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1093\/IJNP\/PYAB062","volume":"25","author":"M Watanabe","year":"2022","unstructured":"Watanabe M, Marcy B, Hiroki A et al (2022) Evaluation of the safety, tolerability, and pharmacokinetic profiles of TP0473292 (TS-161), a prodrug of a novel orthosteric mGlu2\/3 receptor antagonist TP0178894, in healthy subjects and its antidepressant-like effects in rodents. Int J Neuropsychopharmacol 25:106\u2013117. https:\/\/doi.org\/10.1093\/IJNP\/PYAB062","journal-title":"Int J Neuropsychopharmacol"},{"key":"1875_CR93","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.18M12470","author":"D Umbricht","year":"2020","unstructured":"Umbricht D, Niggli M, Sanwald-Ducray P et al (2020) Randomized, double-blind, placebo-controlled trial of the mglu2\/3 negative allosteric modulator decoglurant in partially refractory major depressive disorder. J Clin Psychiatry. https:\/\/doi.org\/10.4088\/JCP.18M12470","journal-title":"J Clin Psychiatry"},{"key":"1875_CR94","doi-asserted-by":"publisher","DOI":"10.1016\/J.PBB.2022.173446","volume":"219","author":"JM Witkin","year":"2022","unstructured":"Witkin JM, Pandey KP, Smith JL (2022) Clinical investigations of compounds targeting metabotropic glutamate receptors. Pharmacol Biochem Behav 219:173446. https:\/\/doi.org\/10.1016\/J.PBB.2022.173446","journal-title":"Pharmacol Biochem Behav"},{"key":"1875_CR95","doi-asserted-by":"publisher","DOI":"10.1177\/2470547019837712","author":"S Chaki","year":"2019","unstructured":"Chaki S, Koike H, Fukumoto K (2019) Targeting of metabotropic glutamate receptors for the development of novel antidepressants. Chronic Stress (Thousand Oaks). https:\/\/doi.org\/10.1177\/2470547019837712","journal-title":"Chronic Stress (Thousand Oaks)"},{"key":"1875_CR96","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEUROPHARM.2022.109308","author":"A Suzuki","year":"2023","unstructured":"Suzuki A, Hara H, Kimura H (2023) Role of the AMPA receptor in antidepressant effects of ketamine and potential of AMPA receptor potentiators as a novel antidepressant. Neuropharmacology. https:\/\/doi.org\/10.1016\/J.NEUROPHARM.2022.109308","journal-title":"Neuropharmacology"},{"key":"1875_CR97","doi-asserted-by":"publisher","first-page":"2816","DOI":"10.1016\/J.DRUDIS.2021.07.027","volume":"26","author":"B Kadriu","year":"2021","unstructured":"Kadriu B, Musazzi L, Johnston JN et al (2021) Positive AMPA receptor modulation in the treatment of neuropsychiatric disorders: a long and winding road. Drug Discov Today 26:2816\u20132838. https:\/\/doi.org\/10.1016\/J.DRUDIS.2021.07.027","journal-title":"Drug Discov Today"},{"key":"1875_CR98","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1177\/0269881112458728","volume":"26","author":"P Dogterom","year":"2012","unstructured":"Nations KR, Dogterom P, Bursi R et al (2012) Examination of Org 26576, an AMPA receptor positive allosteric modulator, in patients diagnosed with major depressive disorder: an exploratory, randomized, double-blind, placebo-controlled trial. J Psychopharmacol 26:1525\u20131539. https:\/\/doi.org\/10.1177\/0269881112458728","journal-title":"J Psychopharmacol"},{"key":"1875_CR99","doi-asserted-by":"publisher","DOI":"10.1038\/S41398-022-02148-W","author":"F Dijkstra","year":"2022","unstructured":"Dijkstra F, O\u2019Donnell P, Klaassen E et al (2022) Central nervous system effects of TAK-653, an investigational alpha-amino-3-hydroxy-5-methyl-4-isoxazole receptor (AMPAR) positive allosteric modulator in healthy volunteers. Transl Psychiatry. https:\/\/doi.org\/10.1038\/S41398-022-02148-W","journal-title":"Transl Psychiatry"},{"key":"1875_CR100","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1113\/JP276698","volume":"599","author":"E Jacobi","year":"2021","unstructured":"Jacobi E, Von Engelhardt J, Forsythe I, B\u00e9\u00a8\u0131que J-CB (2021) Modulation of information processing by AMPA receptor auxiliary subunits. J Physiol 599:471\u2013483. https:\/\/doi.org\/10.1113\/JP276698","journal-title":"J Physiol"},{"key":"1875_CR101","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/J.BPSGOS.2022.02.007","volume":"3","author":"JG He","year":"2023","unstructured":"He JG, Zhou HY, Wang F, Chen JG (2023) Dysfunction of glutamatergic synaptic transmission in depression: focus on ampa receptor trafficking. Biol Psychiatry Glob Open Sci 3:187. https:\/\/doi.org\/10.1016\/J.BPSGOS.2022.02.007","journal-title":"Biol Psychiatry Glob Open Sci"},{"issue":"14","key":"1875_CR102","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-023-42780-8","volume":"1","author":"SG Xue","year":"2023","unstructured":"Xue SG, He JG, Lu LL et al (2023) Enhanced TARP-\u03b38-PSD-95 coupling in excitatory neurons contributes to the rapid antidepressant-like action of ketamine in male mice. Nat Commun 1(14):1\u201316. https:\/\/doi.org\/10.1038\/s41467-023-42780-8","journal-title":"Nat Commun"},{"key":"1875_CR103","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1080\/14656566.2023.2281582\/SUPPL_FILE\/IEOP_A_2281582_SM1604.DOCX","volume":"24","author":"M Kalfas","year":"2023","unstructured":"Kalfas M, Taylor RH, Tsapekos D, Young AH (2023) Psychedelics for treatment resistant depression: are they game changers? Expert Opin Pharmacother 24:2117\u20132132. https:\/\/doi.org\/10.1080\/14656566.2023.2281582\/SUPPL_FILE\/IEOP_A_2281582_SM1604.DOCX","journal-title":"Expert Opin Pharmacother"},{"key":"1875_CR104","doi-asserted-by":"publisher","DOI":"10.1016\/J.PSYCHRES.2023.115531","volume":"329","author":"S Haikazian","year":"2023","unstructured":"Haikazian S, Chen-Li DCJ, Johnson DE et al (2023) Psilocybin-assisted therapy for depression: a systematic review and meta-analysis. Psychiatry Res 329:115531. https:\/\/doi.org\/10.1016\/J.PSYCHRES.2023.115531","journal-title":"Psychiatry Res"},{"key":"1875_CR105","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/J.EURONEURO.2023.07.011","volume":"76","author":"N Perez","year":"2023","unstructured":"Perez N, Langlest F, Mallet L et al (2023) Psilocybin-assisted therapy for depression: a systematic review and dose-response meta-analysis of human studies. Eur Neuropsychopharmacol 76:61\u201376. https:\/\/doi.org\/10.1016\/J.EURONEURO.2023.07.011","journal-title":"Eur Neuropsychopharmacol"},{"key":"1875_CR106","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1007\/S40263-022-00964-8","volume":"36","author":"S Vaidya","year":"2022","unstructured":"Vaidya S, Guerin AA, Walker LC, Lawrence AJ (2022) Clinical effectiveness of muscarinic receptor-targeted interventions in neuropsychiatric disorders: a systematic review. CNS Drugs 36:1171\u20131206. https:\/\/doi.org\/10.1007\/S40263-022-00964-8","journal-title":"CNS Drugs"},{"key":"1875_CR107","doi-asserted-by":"publisher","DOI":"10.3390\/BIOMEDICINES11102636","author":"P Mo\u0107ko","year":"2023","unstructured":"Mo\u0107ko P, \u015aladowska K, Kawalec P et al (2023) The potential of scopolamine as an antidepressant in major depressive disorder: a systematic review of randomized controlled trials. Biomedicines. https:\/\/doi.org\/10.3390\/BIOMEDICINES11102636","journal-title":"Biomedicines"},{"key":"1875_CR108","doi-asserted-by":"publisher","first-page":"11","DOI":"10.2174\/1570159X14666160309114","volume":"15","author":"ES Wohleb","year":"2017","unstructured":"Wohleb ES, Gerhard D, Thomas A, Duman RS (2017) Molecular and cellular mechanisms of rapid-acting antidepressants ketamine and scopolamine. Curr Neuropharmacol 15:11\u201320. https:\/\/doi.org\/10.2174\/1570159X14666160309114","journal-title":"Curr Neuropharmacol"},{"key":"1875_CR109","doi-asserted-by":"publisher","DOI":"10.3389\/FPSYT.2021.724606\/BIBTEX","volume":"12","author":"CMH de Vos","year":"2021","unstructured":"de Vos CMH, Mason NL, Kuypers KPC (2021) Psychedelics and neuroplasticity: a systematic review unraveling the biological underpinnings of psychedelics. Front Psychiatry 12:724606. https:\/\/doi.org\/10.3389\/FPSYT.2021.724606\/BIBTEX","journal-title":"Front Psychiatry"},{"key":"1875_CR110","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1016\/J.TIPS.2021.08.003","volume":"42","author":"LR Aleksandrova","year":"2021","unstructured":"Aleksandrova LR, Phillips AG (2021) Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics. Trends Pharmacol Sci 42:929\u2013942. https:\/\/doi.org\/10.1016\/J.TIPS.2021.08.003","journal-title":"Trends Pharmacol Sci"}],"container-title":["European Archives of Psychiatry and Clinical Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00406-024-01875-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00406-024-01875-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00406-024-01875-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T12:15:44Z","timestamp":1759752944000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00406-024-01875-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,29]]},"references-count":110,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["1875"],"URL":"https:\/\/doi.org\/10.1007\/s00406-024-01875-z","relation":{},"ISSN":["0940-1334","1433-8491"],"issn-type":[{"value":"0940-1334","type":"print"},{"value":"1433-8491","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,29]]},"assertion":[{"value":"30 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 August 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":"Christine Reif-Leonhard received speaker\u2019s and consultant honoraria from Janssen, LivaNova and Das Fortbildungskolleg. Andreas Reif received speaker\u2019s and consultant honoraria from Janssen, Boehringer Ingelheim, COMPASS, SAGE\/Biogen, LivaNova, Shire\/Takeda, MSD and cyclerion. Florian Freudenberg reports no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}