{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:26:24Z","timestamp":1774484784619,"version":"3.50.1"},"reference-count":68,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T00:00:00Z","timestamp":1699920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023275","name":"Translational Cancer Research Network","doi-asserted-by":"crossref","award":["13114323"],"award-info":[{"award-number":["13114323"]}],"id":[{"id":"10.13039\/501100023275","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Ketamine at subanaesthetic dosages (\u22640.5mg\/kg) exhibits rapid onset (over hours to days) antidepressant effects against major depressive disorder in people who are otherwise well. However, its safety, tolerability and efficacy are not known for major depressive disorder in people with advanced life-limiting illnesses.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>To determine the feasibility, safety, tolerability, acceptability and any antidepressant signal\/activity to justify and inform a fully powered study of subcutaneous ketamine infusions for major depressive disorder in the palliative setting.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This was a single arm, open-label, phase II feasibility study (Australian New Zealand Clinical Trial Registry Number\u2014ACTRN12618001586202). We recruited adults (\u2265 18-years-old) with advanced life-limiting illnesses referred to four palliative care services in Sydney, Australia, diagnosed with major depressive disorder from any care setting. Participants received weekly subcutaneous ketamine infusion (0.1\u20130.4mg\/kg) over two hours using individual dose-titration design. Outcomes assessed were feasibility, safety, tolerability and antidepressant activity.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>Out of ninety-nine referrals, ten participants received ketamine and were analysed for responses. Accrual rate was 0.54 participants\/month across sites with 50% of treated participants achieving \u2265 50% reduction in baseline Montgomery-\u00c5sberg Depression Rating Scale, meeting feasibility criteria set <jats:italic>a priori<\/jats:italic>. There were no clinically relevant harms encountered.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>A future definitive trial exploring the effectiveness of subcutaneous infusion of ketamine for major depressive disorder in the palliative care setting may be feasible by addressing identified study barriers. Individual dose-titration of subcutaneous ketamine infusions over two hours from 0.1mg\/kg can be well-tolerated and appears to produce transient antidepressant signals over hours to days.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0290876","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T18:29:40Z","timestamp":1699986580000},"page":"e0290876","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Subcutaneous ketamine infusion in palliative patients for major depressive disorder (SKIPMDD)\u2014Phase II single-arm open-label feasibility study"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8018-9362","authenticated-orcid":true,"given":"Wei","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caitlin","family":"Sheehan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1506-9572","authenticated-orcid":true,"given":"Richard","family":"Chye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sungwon","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Bayes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colleen","family":"Loo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Draper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meera R.","family":"Agar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David C.","family":"Currow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,11,14]]},"reference":[{"issue":"1","key":"pone.0290876.ref001","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1472-684X-13-10","article-title":"Prevalence and risk factors of depressive symptoms in a Canadian palliative home care population: a cross-sectional study","volume":"13","author":"KA Fisher","year":"2014","journal-title":"BMC Palliat Care"},{"issue":"3","key":"pone.0290876.ref002","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1089\/jpm.2006.9.751","article-title":"Psychological issues in end-of-life care","volume":"9","author":"SD Block","year":"2006","journal-title":"J Palliat Med"},{"issue":"1","key":"pone.0290876.ref003","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.jpainsymman.2020.07.011","article-title":"Clinically Significant Depressive Symptoms are Prevalent in People with Extremely Short Prognoses-A Systematic Review","volume":"61","author":"W Lee","year":"2021","journal-title":"J Pain Symptom Manage"},{"issue":"2","key":"pone.0290876.ref004","first-page":"81","article-title":"Depression in advanced disease: A systematic review part 1 prevalence and case finding","volume":"16","author":"M Hotopf","year":"2002","journal-title":"Palliat Med"},{"issue":"2","key":"pone.0290876.ref005","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/S1470-2045(11)70002-X","article-title":"Prevalence of depression, anxiety, and adjustment disorder in oncological, haematological, and palliative-care settings: a meta-analysis of 94 interview-based studies","volume":"12","author":"AJ Mitchell","year":"2011","journal-title":"Lancet Oncol"},{"issue":"22","key":"pone.0290876.ref006","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1001\/jama.284.22.2907","article-title":"Depression, hopelessness, and desire for hastened death in terminally ill patients with cancer","volume":"284","author":"W Breitbart","year":"2000","journal-title":"JAMA"},{"issue":"3","key":"pone.0290876.ref007","first-page":"209","article-title":"Assessing and managing depression in the terminally ill patient. 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