{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T05:06:37Z","timestamp":1778907997835,"version":"3.51.4"},"reference-count":35,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014630","name":"Minist\u00e8re des Solidarit\u00e9s et de la Sant\u00e9","doi-asserted-by":"publisher","award":["PHRCI-17-042"],"award-info":[{"award-number":["PHRCI-17-042"]}],"id":[{"id":"10.13039\/501100014630","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009243","name":"Direction G\u00e9n\u00e9rale de l\u2019offre de Soins","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009243","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","thelancet.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["eClinicalMedicine"],"published-print":{"date-parts":[[2026,4]]},"DOI":"10.1016\/j.eclinm.2026.103860","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T19:15:40Z","timestamp":1775157340000},"page":"103860","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Nitrous oxide for late-life depression with inadequate antidepressant response: a randomised controlled trial"],"prefix":"10.1016","volume":"94","author":[{"given":"Antony","family":"Salam\u00e9","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Bulteau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Robert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana\u00efs","family":"Vandevelde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Val\u00e9rie","family":"Gissot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Sara","family":"Agier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quentin","family":"Gallet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques-Alexis","family":"Nkodo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoire","family":"Leroy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Brunault","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9l\u00e8ne","family":"Bourgoin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Arlicot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabien","family":"Espitalier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6734-5685","authenticated-orcid":false,"given":"Am\u00e9lie","family":"Le Gouge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3877-0855","authenticated-orcid":false,"given":"Wissam","family":"El-Hage","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Camus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1946-1686","authenticated-orcid":false,"given":"Pierre","family":"Poupin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0949-8389","authenticated-orcid":false,"given":"Thomas","family":"Desmidt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"4","key":"10.1016\/j.eclinm.2026.103860_bib1","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.psc.2013.08.008","article-title":"The economic, public health, and caregiver burden of late-life depression","volume":"36","author":"Zivin","year":"2013","journal-title":"Psychiatr Clin North Am"},{"issue":"3","key":"10.1016\/j.eclinm.2026.103860_bib2","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S0165-0327(01)00413-X","article-title":"Excess mortality in depression: a meta-analysis of community studies","volume":"72","author":"Cuijpers","year":"2002","journal-title":"J Affect Disord"},{"issue":"2","key":"10.1016\/j.eclinm.2026.103860_bib3","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1097\/PSY.0000000000000763","article-title":"The association of comorbid depression and anxiety symptoms with disability onset in older adults","volume":"82","author":"Dong","year":"2020","journal-title":"Psychosom Med"},{"issue":"1","key":"10.1016\/j.eclinm.2026.103860_bib4","doi-asserted-by":"crossref","DOI":"10.1136\/bmjment-2024-301324","article-title":"Effectiveness of pharmacological and non-pharmacological interventions for treatment-resistant depression in older patients: a systematic review and meta-analysis","volume":"28","author":"Larsen","year":"2025","journal-title":"BMJ Ment Health"},{"issue":"2","key":"10.1016\/j.eclinm.2026.103860_bib5","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/sj.ejcn.1602066","article-title":"Lower resting metabolic rate in the elderly may not be entirely due to changes in body composition","volume":"59","author":"Krems","year":"2005","journal-title":"Eur J Clin Nutr"},{"issue":"1","key":"10.1016\/j.eclinm.2026.103860_bib6","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1046\/j.1365-2125.2003.02007.x","article-title":"Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications","volume":"57","author":"Mangoni","year":"2004","journal-title":"Br J Clin Pharmacol"},{"issue":"2","key":"10.1016\/j.eclinm.2026.103860_bib7","first-page":"97","article-title":"Polypharmacy among the elderly","volume":"9","author":"Hosseini","year":"2018","journal-title":"J Midlife Health"},{"issue":"4","key":"10.1016\/j.eclinm.2026.103860_bib8","doi-asserted-by":"crossref","DOI":"10.33552\/GJAGR.2021.01.000518","article-title":"Prevalence of comorbidity among elderly","volume":"1","author":"Alsuwaidan","year":"2021","journal-title":"GJAGR"},{"issue":"12","key":"10.1016\/j.eclinm.2026.103860_bib9","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.4088\/JCP.10r06531","article-title":"Efficacy of antidepressants for late-life depression: a meta-analysis and meta-regression of placebo-controlled randomized trials","volume":"72","author":"Tedeschini","year":"2011","journal-title":"J Clin Psychiatry"},{"issue":"4","key":"10.1016\/j.eclinm.2026.103860_bib10","doi-asserted-by":"crossref","DOI":"10.2196\/medinform.6437","article-title":"Population analysis of adverse events in different age groups using big clinical trials data","volume":"4","author":"Luo","year":"2016","journal-title":"JMIR Med Inform"},{"issue":"1","key":"10.1016\/j.eclinm.2026.103860_bib11","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.biopsych.2014.11.016","article-title":"Nitrous oxide for treatment-resistant major depression: a proof-of-concept trial","volume":"78","author":"Nagele","year":"2015","journal-title":"Biol Psychiatry"},{"key":"10.1016\/j.eclinm.2026.103860_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2025.106023","article-title":"Nitrous oxide for the treatment of depression: a systematic review and meta-analysis","volume":"122","author":"Gill","year":"2025","journal-title":"eBioMedicine"},{"issue":"6","key":"10.1016\/j.eclinm.2026.103860_bib13","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1093\/bja\/aen085","article-title":"Effect of nitrous oxide on plasma homocysteine and folate in patients undergoing major surgery","volume":"100","author":"Myles","year":"2008","journal-title":"Br J Anaesth"},{"key":"10.1016\/j.eclinm.2026.103860_bib14","doi-asserted-by":"crossref","DOI":"10.1038\/s41380-025-03439-6","article-title":"Rapid antidepressant potential of nitrous oxide: current state and major questions","author":"Zorumski","year":"2025","journal-title":"Mol Psychiatry"},{"issue":"1","key":"10.1016\/j.eclinm.2026.103860_bib15","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.biopsych.2015.04.007","article-title":"Potential pathways involved in the rapid antidepressant effects of nitrous oxide","volume":"78","author":"Zarate","year":"2015","journal-title":"Biol Psychiatry"},{"issue":"1","key":"10.1016\/j.eclinm.2026.103860_bib16","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.1038\/s41467-025-57951-y","article-title":"Nitrous oxide activates layer 5 prefrontal neurons via SK2 channel inhibition for antidepressant effect","volume":"16","author":"Cichon","year":"2025","journal-title":"Nat Commun"},{"issue":"9","key":"10.1016\/j.eclinm.2026.103860_bib17","doi-asserted-by":"crossref","first-page":"3900","DOI":"10.1038\/s41380-023-02217-6","article-title":"Changes in cerebral connectivity and brain tissue pulsations with the antidepressant response to an equimolar mixture of oxygen and nitrous oxide: an MRI and ultrasound study","volume":"28","author":"Desmidt","year":"2023","journal-title":"Mol Psychiatry"},{"issue":"1","key":"10.1016\/j.eclinm.2026.103860_bib18","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1213\/00000539-197601000-00013","article-title":"The pulmonary absorption-excretion volume effect","volume":"55","author":"Rackow","year":"1976","journal-title":"Anesth Analg"},{"issue":"4","key":"10.1016\/j.eclinm.2026.103860_bib19","doi-asserted-by":"crossref","first-page":"124","DOI":"10.2344\/0003-3006-55.4.124","article-title":"Nitrous oxide and the inhalation anesthetics","volume":"55","author":"Becker","year":"2008","journal-title":"Anesth Prog"},{"issue":"6","key":"10.1016\/j.eclinm.2026.103860_bib20","doi-asserted-by":"crossref","first-page":"501","DOI":"10.2165\/00002512-200724060-00006","article-title":"Tolerability of an equimolar mix of nitrous oxide and oxygen during painful procedures in very elderly patients","volume":"24","author":"Bauer","year":"2007","journal-title":"Drugs Aging"},{"key":"10.1016\/j.eclinm.2026.103860_bib21","doi-asserted-by":"crossref","first-page":"67","DOI":"10.2147\/CIA.S4381","article-title":"Interest of 50% nitrous oxide and oxygen premix sedation in gerodontology","volume":"67","author":"Nicolas","year":"2008","journal-title":"Clin Interv Aging"},{"issue":"4","key":"10.1016\/j.eclinm.2026.103860_bib22","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.bpsgos.2023.01.006","article-title":"Persistent brain connectivity changes in healthy volunteers following nitrous oxide inhalation","volume":"3","author":"Palanca","year":"2023","journal-title":"Biol Psychiatry Glob Open Sci"},{"issue":"7","key":"10.1016\/j.eclinm.2026.103860_bib23","article-title":"Nitrous oxide-induced vitamin B12 deficiency resulting in myelopathy","volume":"12","author":"Campdesuner","year":"2020","journal-title":"Cureus"},{"issue":"5","key":"10.1016\/j.eclinm.2026.103860_bib25","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S0022-3956(97)00029-0","article-title":"The use of visual analog scales in mood disorders: a critical review","volume":"31","author":"Ahearn","year":"1997","journal-title":"J Psychiatr Res"},{"issue":"2","key":"10.1016\/j.eclinm.2026.103860_bib26","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0229381","article-title":"Efficacy of new-generation antidepressants assessed with the Montgomery-Asberg depression rating scale, the gold standard clinician rating scale: a meta-analysis of randomised placebo-controlled trials","volume":"15","author":"Hengartner","year":"2020","journal-title":"PLoS One"},{"issue":"1","key":"10.1016\/j.eclinm.2026.103860_bib27","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1471-2288-3-22","article-title":"How many repeated measures in repeated measures designs? Statistical issues for comparative trials","volume":"3","author":"Vickers","year":"2003","journal-title":"BMC Med Res Methodol"},{"issue":"12","key":"10.1016\/j.eclinm.2026.103860_bib28","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1016\/j.jclinepi.2007.02.006","article-title":"A simple sample size formula for analysis of covariance in randomized clinical trials","volume":"60","author":"Borm","year":"2007","journal-title":"J Clin Epidemiol"},{"key":"10.1016\/j.eclinm.2026.103860_bib29","doi-asserted-by":"crossref","DOI":"10.1016\/j.psychres.2022.114867","article-title":"Efficacy and safety of nitrous oxide for patients with treatment-resistant depression, a randomized controlled trial","volume":"317","author":"Yan","year":"2022","journal-title":"Psychiatry Res"},{"issue":"4","key":"10.1016\/j.eclinm.2026.103860_bib30","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.biopsych.2012.06.022","article-title":"Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression","volume":"74","author":"Murrough","year":"2013","journal-title":"Biol Psychiatry"},{"issue":"11","key":"10.1016\/j.eclinm.2026.103860_bib31","doi-asserted-by":"crossref","first-page":"3229","DOI":"10.1007\/s00213-021-05939-z","article-title":"Age affects temporal response, but not durability, to serial ketamine infusions for treatment refractory depression","volume":"238","author":"Pennybaker","year":"2021","journal-title":"Psychopharmacology"},{"issue":"3","key":"10.1016\/j.eclinm.2026.103860_bib32","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/bdi.13288","article-title":"Proof-of-concept randomized controlled trial of single-session nitrous oxide treatment for refractory bipolar depression: focus on cerebrovascular target engagement","volume":"25","author":"Kim","year":"2023","journal-title":"Bipolar Disord"},{"issue":"597","key":"10.1016\/j.eclinm.2026.103860_bib33","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abe1376","article-title":"A phase 2 trial of inhaled nitrous oxide for treatment-resistant major depression","volume":"13","author":"Nagele","year":"2021","journal-title":"Sci Transl Med"},{"issue":"7","key":"10.1016\/j.eclinm.2026.103860_bib34","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1038\/s41386-019-0317-8","article-title":"Impact of midazolam vs. saline on effect size estimates in controlled trials of ketamine as a rapid-acting antidepressant","volume":"44","author":"Wilkinson","year":"2019","journal-title":"Neuropsychopharmacol"},{"issue":"1","key":"10.1016\/j.eclinm.2026.103860_bib35","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0010-440X(96)90047-4","article-title":"Reduction in dissociation due to aging and cognitive deficit","volume":"37","author":"Walker","year":"1996","journal-title":"Compr Psychiatry"},{"issue":"1","key":"10.1016\/j.eclinm.2026.103860_bib36","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-98245-9","article-title":"Normobaric oxygen treatment for mild-to-moderate depression: a randomized, double-blind, proof-of-concept trial","volume":"11","author":"Bloch","year":"2021","journal-title":"Sci Rep"}],"container-title":["eClinicalMedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589537026001070?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589537026001070?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T04:08:04Z","timestamp":1778904484000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589537026001070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":35,"alternative-id":["S2589537026001070"],"URL":"https:\/\/doi.org\/10.1016\/j.eclinm.2026.103860","relation":{},"ISSN":["2589-5370"],"issn-type":[{"value":"2589-5370","type":"print"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Nitrous oxide for late-life depression with inadequate antidepressant response: a randomised controlled trial","name":"articletitle","label":"Article Title"},{"value":"eClinicalMedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.eclinm.2026.103860","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"103860"}}