{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T15:30:54Z","timestamp":1793374254736,"version":"4.5.0"},"reference-count":30,"publisher":"Royal College of Psychiatrists","issue":"6","license":[{"start":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:00:00Z","timestamp":1689292800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1105089"],"award-info":[{"award-number":["APP1105089"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Br J Psychiatry"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:sec id=\"S000712502300079X_sec_a1\"><jats:title>Background<\/jats:title><jats:p>Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.<\/jats:p><\/jats:sec><jats:sec id=\"S000712502300079X_sec_a2\"><jats:title>Aims<\/jats:title><jats:p>To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at <jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.anzctr.org.au\">www.anzctr.org.au<\/jats:uri>.<\/jats:p><\/jats:sec><jats:sec id=\"S000712502300079X_sec_a3\" sec-type=\"methods\"><jats:title>Method<\/jats:title><jats:p>This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg\/kg versus midazolam 0.025 mg\/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5\u20130.9 mg\/kg or midazolam 0.025\u20130.045 mg\/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-\u00c5sberg Rating Scale for Depression score \u226410) at the end of week 4.<\/jats:p><\/jats:sec><jats:sec id=\"S000712502300079X_sec_a4\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% <jats:italic>v<\/jats:italic>. 2.0%; OR = 12.1, 95% CI 2.1\u201369.2, <jats:italic>P<\/jats:italic> = 0.005), but not different in cohort 1 (remission rate 6.3% <jats:italic>v<\/jats:italic>. 8.8%; OR = 1.3, 95% CI 0.2\u20138.2, <jats:italic>P<\/jats:italic> = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h.<\/jats:p><\/jats:sec><jats:sec id=\"S000712502300079X_sec_a5\" sec-type=\"conclusions\"><jats:title>Conclusions<\/jats:title><jats:p>Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.<\/jats:p><\/jats:sec>","DOI":"10.1192\/bjp.2023.79","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T01:00:51Z","timestamp":1689296451000},"page":"533-541","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":72,"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"],"prefix":"10.1192","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3267-0554","authenticated-orcid":false,"given":"Colleen","family":"Loo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0476-9146","authenticated-orcid":false,"given":"Nick","family":"Glozier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Barton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard T.","family":"Baune","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie T.","family":"Mills","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Fitzgerald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Glue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanthi","family":"Sarma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Galvez-Ortiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dusan","family":"Hadzi-Pavlovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Alonzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donel","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4440-9273","authenticated-orcid":false,"given":"Stevan","family":"Nikolin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7954-5235","authenticated-orcid":false,"given":"Philip B.","family":"Mitchell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Berk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Carter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maree","family":"Hackett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Leyden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2852-7923","authenticated-orcid":false,"given":"Sean","family":"Hood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew A.","family":"Somogyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Lapidus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Stratton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Gainsford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Garg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5939-1339","authenticated-orcid":false,"given":"Nicollette L. 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