{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T22:51:59Z","timestamp":1791672719536,"version":"4.3.4"},"reference-count":55,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Affective Disorders"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1016\/j.jad.2025.120475","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T22:39:08Z","timestamp":1760654348000},"page":"120475","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"PA","title":["Efficacy and safety of ketamine maintenance therapy in treatment-resistant depression: A systematic review of treatment protocols and clinical outcomes"],"prefix":"10.1016","volume":"394","author":[{"given":"Abdulaziz M.","family":"Al-Garni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Vazquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tariq","family":"Alotibi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Hernandorena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliya","family":"Knyahnytska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jad.2025.120475_bb0005","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.jpsychires.2022.04.037","article-title":"Real-world effectiveness of ketamine in treatment-resistant depression: a systematic review & meta-analysis","volume":"151","author":"Alnefeesi","year":"2022","journal-title":"J. Psychiatr. Res."},{"issue":"1","key":"10.1016\/j.jad.2025.120475_bb0010","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijchp.2023.100428","article-title":"The efficacy and safety of ketamine for depression in patients with cancer: a systematic review","volume":"24","author":"Azari","year":"2024","journal-title":"Int. J. Clin. Health Psychol."},{"key":"10.1016\/j.jad.2025.120475_bb0015","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s13670-023-00389-1","article-title":"A new solution to an age-old problem: a review of ketamine and esketamine for treatment-resistant depression in late life","volume":"12","author":"Balaram","year":"2023","journal-title":"Curr. Geriatr. Rep."},{"key":"10.1016\/j.jad.2025.120475_bb0020","series-title":"Clinical Indicators of the Suicide Crisis and Response to Ketamine","author":"Ballard","year":"2024"},{"key":"10.1016\/j.jad.2025.120475_bb0025","series-title":"The Pharmacological Frontiers in Treatment Resistant Major Depression","author":"Birkenh\u00e4ger","year":"2013"},{"issue":"1","key":"10.1016\/j.jad.2025.120475_bb0030","doi-asserted-by":"crossref","DOI":"10.1007\/s44202-024-00277-5","article-title":"Understanding the variability in ketamine\u2019s efficacy in managing treatment-resistant depression","volume":"4","author":"Bryan","year":"2024","journal-title":"Discov. Psychol."},{"key":"10.1016\/j.jad.2025.120475_bb0035","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.jad.2024.04.039","article-title":"Number needed to treat (NNT) for ketamine and esketamine in adults with treatment-resistant depression: a systematic review and meta- analysis","volume":"356","author":"Calder","year":"2024","journal-title":"J. Affect. Disord."},{"issue":"Suppl. 1","key":"10.1016\/j.jad.2025.120475_bb0040","doi-asserted-by":"crossref","first-page":"S608","DOI":"10.1192\/j.eurpsy.2023.1270","article-title":"Efficacy and clinical and neuroimaging biomarkers of response of two intensive and spaced treatment protocols of theta burst magnetic stimulation in treatment resistant depression","volume":"66","author":"Ca\u00f1ada","year":"2023","journal-title":"Eur. Psychiatry"},{"key":"10.1016\/j.jad.2025.120475_bb0045","series-title":"Combination of Intravenous Ketamine and Electroconvulsotherapy for Treatment-resistant Depression: A Systematic Review","article-title":"et al","author":"Capa","year":"2023"},{"issue":"8","key":"10.1016\/j.jad.2025.120475_bb0050","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s40263-023-01026-3","article-title":"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","volume":"37","author":"Castro","year":"2023","journal-title":"CNS Drugs"},{"issue":"9","key":"10.1016\/j.jad.2025.120475_bb0055","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1007\/s40263-021-00846-5","article-title":"Prevention and management of common adverse effects of ketamine and esketamine in patients with mood disorders","volume":"35","author":"Ceban","year":"2021","journal-title":"CNS Drugs"},{"key":"10.1016\/j.jad.2025.120475_bb0060","series-title":"Effect of Intravenous Ketamine on Suicidality in Adults With Treatment-resistant Depression: A Real World Effectiveness Study","first-page":"116282","author":"Chen-Li","year":"2024"},{"issue":"4","key":"10.1016\/j.jad.2025.120475_bb0065","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1111\/acps.13605","article-title":"Exploring the potential of a bridge therapy: synergistic approach integrating intravenous ketamine and intranasal esketamine for treatment-resistant depression","volume":"148","author":"D\u2019Andrea","year":"2023","journal-title":"Acta Psychiatr. Scand."},{"issue":"8","key":"10.1016\/j.jad.2025.120475_bb0070","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1038\/s41386-020-0663-6","article-title":"Ketamine metabolites, clinical response, and gamma power in a randomized, placebo-controlled, crossover trial for treatment-resistant major depression","volume":"45","author":"Farmer","year":"2020","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.jad.2025.120475_bb0075","doi-asserted-by":"crossref","DOI":"10.3389\/fpsyt.2024.1476248","article-title":"Neurofilament light chain plasma levels in major depressive disorder: a brief research report","volume":"15","author":"Fern\u00e1ndez-Pereira","year":"2024","journal-title":"Front. Psychiatry"},{"key":"10.1016\/j.jad.2025.120475_bb0080","first-page":"1","article-title":"A pain physician and anesthesiologist\u2019s perspective on ketamine for treatment-resistant depression","volume":"5","author":"Gatewood","year":"2023"},{"issue":"2","key":"10.1016\/j.jad.2025.120475_bb0085","first-page":"134","article-title":"Defining treatment-resistant depression","volume":"37","author":"Gaynes","year":"2020"},{"key":"10.1016\/j.jad.2025.120475_bb0090","series-title":"Identifying Efficacy Variables for the Use of Escitalopram in Mild Major Depression Disorder (MDD): Implications for Treatment-resistant MDD Trials","author":"Geraci","year":"2024"},{"key":"10.1016\/j.jad.2025.120475_bb0095","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.bbi.2024.11.035","article-title":"Plasma levels of matrix metalloproteinases in early psychosis, anxiety and depression: evidence from the ALSPAC cohort","volume":"124","author":"Ghelfi","year":"2025","journal-title":"Brain Behav. Immun."},{"key":"10.1016\/j.jad.2025.120475_bb0100","article-title":"Economic evaluation of interventions for treatment-resistant depression: a systematic review","volume":"14","author":"Hannah","year":"2023","journal-title":"Front. Psych."},{"issue":"1","key":"10.1016\/j.jad.2025.120475_bb0105","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1093\/ijnp\/pyaa068","article-title":"Esketamine nasal spray for rapid reduction of depressive symptoms in patients with major depressive disorder who have active suicide ideation with intent: results of a phase 3, double-blind, randomized study (ASPIRE II)","volume":"24","author":"Ionescu","year":"2021","journal-title":"Int. J. Neuropsychopharmacol."},{"issue":"1","key":"10.1016\/j.jad.2025.120475_bb0110","doi-asserted-by":"crossref","first-page":"70","DOI":"10.9758\/cpn.2022.20.1.70","article-title":"Long-term safety and efficacy of esketamine nasal spray plus an oral antidepressant in patients with treatment-resistant depression- an Asian sub-group analysis from the SUSTAIN-2 study","volume":"20","author":"Jeon","year":"2022","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"10.1016\/j.jad.2025.120475_bb0115","doi-asserted-by":"crossref","first-page":"4","DOI":"10.4088\/JCP.psprmdd2408ah","article-title":"Difficult to treat depression","volume":"85","author":"Karp","year":"2024","journal-title":"J. Clin. Psychiatry"},{"issue":"4","key":"10.1016\/j.jad.2025.120475_bb0120","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.neurom.2023.12.004","article-title":"Combination of acute and maintenance esketamine treatment with adjunctive long-term Vagus nerve stimulation in difficult-to-treat depression","volume":"27","author":"Kavakbasi","year":"2024","journal-title":"Neuromodulation"},{"issue":"3","key":"10.1016\/j.jad.2025.120475_bb0125","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1017\/S1092852924000105","article-title":"Effects of esketamine nasal spray on depressive symptom severity in adults with treatment-resistant depression and associations between the Montgomery-\u00c5sberg Depression Rating Scale and the 9-item Patient Health Questionnaire","volume":"29","author":"Kern Sliwa","year":"2024","journal-title":"CNS Spectr."},{"issue":"12","key":"10.1016\/j.jad.2025.120475_bb0130","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.euroneuro.2007.05.004","article-title":"Limitations of current medical treatments for depression: disturbed circadian rhythms as a possible therapeutic target","volume":"17","author":"Lader","year":"2007","journal-title":"Eur. Neuropsychopharmacol."},{"issue":"2","key":"10.1016\/j.jad.2025.120475_bb0135","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S2215-0366(21)00395-3","article-title":"Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990\u20132019: a systematic analysis for the Global Burden of Disease Study 2019","volume":"9","year":"2022","journal-title":"Lancet Psychiatry"},{"issue":"1","key":"10.1016\/j.jad.2025.120475_bb0140","doi-asserted-by":"crossref","DOI":"10.1192\/bjo.2020.132","article-title":"Ketamine treatment for individuals with treatment-resistant depression: longitudinal qualitative interview study of patient experiences","volume":"7","author":"Lascelles","year":"2020","journal-title":"BJPsych Open"},{"key":"10.1016\/j.jad.2025.120475_bb0145","article-title":"Ketamine in the effective management of chronic pain, depression, and posttraumatic stress disorder for Veterans: a meta-analysis and systematic review","volume":"15","author":"Liu","year":"2024","journal-title":"Front. Psych."},{"issue":"6","key":"10.1016\/j.jad.2025.120475_bb2145","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1192\/bjp.2023.79","article-title":"Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial","volume":"223","author":"Loo","year":"2023","journal-title":"Br. J. Psychiatry"},{"key":"10.1016\/j.jad.2025.120475_bb0150","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2023.1223145","article-title":"Antidepressant mechanisms of ketamine: a review of actions with relevance to treatment-resistance and neuroprogression","volume":"17","author":"Lullau","year":"2023","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.jad.2025.120475_bb0155","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.jad.2022.09.043","article-title":"Real-world experience of esketamine use to manage treatment-resistant depression: a multicentric study on safety and effectiveness (REAL-ESK study)","volume":"319","author":"Martinotti","year":"2022","journal-title":"J. Affect. Disord."},{"issue":"5","key":"10.1016\/j.jad.2025.120475_bb0160","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1176\/appi.ajp.2020.20081251","article-title":"Synthesizing the evidence for ketamine and esketamine in treatment-resistant depression: an international expert opinion on the available evidence and implementation","volume":"178","author":"McIntyre","year":"2021","journal-title":"Am. J. Psychiatry"},{"issue":"1","key":"10.1016\/j.jad.2025.120475_bb0165","first-page":"1","article-title":"Personalized use of ketamine and esketamine for treatment-resistant depression","volume":"14","author":"Medeiros","year":"2024"},{"issue":"11","key":"10.1016\/j.jad.2025.120475_bb0170","doi-asserted-by":"crossref","DOI":"10.1093\/ijnp\/pyae046","article-title":"Effect of esketamine nasal spray on cognition in patients with treatment-resistant depression: results from four phase 3 studies","volume":"27","author":"Morrison","year":"2024","journal-title":"Int. J. Neuropsychopharmacol."},{"issue":"10","key":"10.1016\/j.jad.2025.120475_bb0175","first-page":"1635","article-title":"Neurotrophic and synaptic plasticity biomarkers following ketamine administration in treatment-resistant depression","volume":"45","author":"Murrough","year":"2020","journal-title":"Neuropsychopharmacology"},{"issue":"4","key":"10.1016\/j.jad.2025.120475_bb0180","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1007\/s00213-021-05767-1","article-title":"Ketamine-induced urological toxicity: potential mechanisms and translation for adults with mood disorders receiving ketamine treatment","volume":"238","author":"Ng","year":"2021","journal-title":"Psychopharmacology"},{"issue":"9","key":"10.1016\/j.jad.2025.120475_bb0185","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.recesp.2021.06.016","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"74","author":"Page","year":"2021","journal-title":"Rev. Esp. Cardiol. (Engl. Ed.)"},{"issue":"4","key":"10.1016\/j.jad.2025.120475_bb0190","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1097\/PRA.0000000000000723","article-title":"Reduction in cognitive symptoms following intranasal esketamine administration in patients with chronic treatment-resistant depression: a 12-week case series","volume":"29","author":"Pepe","year":"2023","journal-title":"J. Psychiatr. Pract."},{"key":"10.1016\/j.jad.2025.120475_bb0195","doi-asserted-by":"crossref","DOI":"10.1016\/j.pnpbp.2019.109773","article-title":"Leptin, obesity, and response to ketamine","volume":"98","author":"Rashidian","year":"2020","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"issue":"12","key":"10.1016\/j.jad.2025.120475_bb0200","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1001\/jamapsychiatry.2022.3352","article-title":"Efficacy and safety of ketamine vs electroconvulsive therapy among patients with major depressive episode: a systematic review and meta-analysis","volume":"79","author":"Rhee","year":"2022","journal-title":"JAMA Psychiatry"},{"key":"10.1016\/j.jad.2025.120475_bb0205","series-title":"Ketamine Infusion Clinic Reports Real-world Patient Experiences","author":"Richmond","year":"2024"},{"issue":"4","key":"10.1016\/j.jad.2025.120475_bb0210","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1097\/ALN.0000000000005076","article-title":"Management of depression and anxiety in perioperative medicine","volume":"141","author":"Rolfzen","year":"2024","journal-title":"Anesthesiology"},{"issue":"4","key":"10.1016\/j.jad.2025.120475_bb0215","doi-asserted-by":"crossref","DOI":"10.3390\/ijerph15040771","article-title":"Predictors of response to ketamine in treatment resistant major depressive disorder and bipolar disorder","volume":"15","author":"Rong","year":"2018","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"10.1016\/j.jad.2025.120475_bb0220","article-title":"Efficacy and safety of intranasal esketamine in patients with treatment-resistant depression and comorbid chronic post-traumatic stress disorder: open-label single-arm pilot study","volume":"13","author":"Roth\u00e4rmel","year":"2022","journal-title":"Front. Psych."},{"issue":"8","key":"10.1016\/j.jad.2025.120475_bb0225","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s11920-023-01432-w","article-title":"Ketamine use in child and adolescent psychiatry: emerging data in treatment-resistant depression, insights from adults, and future directions","volume":"25","author":"Ryan","year":"2023","journal-title":"Curr. Psychiatry Rep."},{"key":"10.1016\/j.jad.2025.120475_bb0230","article-title":"Current progress and challenges in psychopharmacology research","volume":"15","author":"Sakalem","year":"2024"},{"issue":"11","key":"10.1016\/j.jad.2025.120475_bb0235","first-page":"1037","article-title":"Esketamine in treatment-resistant depression: a narrative review","volume":"33","author":"Sanacora","year":"2019","journal-title":"CNS Drugs"},{"issue":"1","key":"10.1016\/j.jad.2025.120475_bb0240","doi-asserted-by":"crossref","DOI":"10.1192\/bjo.2021.1059","article-title":"Repeated, low-dose oral esketamine in patients with treatment-resistant depression: pilot study","volume":"8","author":"Smith-Apeldoorn","year":"2021","journal-title":"BJPsych Open"},{"issue":"11","key":"10.1016\/j.jad.2025.120475_bb0245","doi-asserted-by":"crossref","DOI":"10.3390\/ph16111572","article-title":"Pharmacotherapies targeting GABA-glutamate neurotransmission for treatment-resistant depression","volume":"16","author":"Vecera","year":"2023","journal-title":"Pharmaceuticals (Basel)"},{"issue":"3","key":"10.1016\/j.jad.2025.120475_bb0250","first-page":"241","article-title":"Functional connectivity between glutamate receptor antagonism and insulin pathways: implications for modeling mechanism of action of ketamine\/esketamine and dextromethorphan in depression treatment","volume":"10","author":"Wong","year":"2025","journal-title":"Biol. Psychiatry Cogn. Neurosci. Neuroimaging"},{"key":"10.1016\/j.jad.2025.120475_bb0255","article-title":"Mental health consequences of the COVID-19 pandemic","volume":"51","author":"Xie","year":"2020","journal-title":"Asian J. Psychiatr."},{"key":"10.1016\/j.jad.2025.120475_bb0260","article-title":"Intravenous ketamine for depression: a clinical discussion reconsidering best practices in acute hypertension management","volume":"13","author":"Yip","year":"2022","journal-title":"Front. Psych."},{"issue":"8","key":"10.1016\/j.jad.2025.120475_bb0265","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1038\/s41386-023-01577-5","article-title":"Long-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: interim results of the SUSTAIN-3 study","volume":"48","author":"Zaki","year":"2023","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.jad.2025.120475_bb0270","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.bbi.2024.11.033","article-title":"Depression with immuno-metabolic dysregulation: testing pragmatic criteria to stratify patients","volume":"124","author":"Zwiep","year":"2025","journal-title":"Brain Behav. Immun."}],"container-title":["Journal of Affective Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0165032725019172?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0165032725019172?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T08:55:33Z","timestamp":1780822533000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0165032725019172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":55,"alternative-id":["S0165032725019172"],"URL":"https:\/\/doi.org\/10.1016\/j.jad.2025.120475","relation":{},"ISSN":["0165-0327"],"issn-type":[{"value":"0165-0327","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Efficacy and safety of ketamine maintenance therapy in treatment-resistant depression: A systematic review of treatment protocols and clinical outcomes","name":"articletitle","label":"Article Title"},{"value":"Journal of Affective Disorders","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jad.2025.120475","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"120475"}}