{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:19:30Z","timestamp":1785435570087,"version":"3.56.0"},"reference-count":26,"publisher":"Royal College of Psychiatrists","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Br J Psychiatry"],"abstract":"<jats:sec id=\"S0007125026106928_as1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Longer-term outcome and safety data of repeated subcutaneous racemic ketamine for treatment-resistant depression (TRD) is lacking, as is knowledge of the impact of prior ketamine treatment on subsequent response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125026106928_as2\">\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To evaluate the effectiveness and safety of a 4-week course of subcutaneous racemic ketamine over 6 months and investigate whether prior ketamine treatment influences treatment response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125026106928_as3\">\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>An open label extension (OLE) of a randomised controlled trial (RCT) was conducted at seven mood disorder centres in Australasia, enrolling consenting trial participants who had a Montgomery-\u00c5sberg Depression Rating Scale (MADRS) score of \u226520 at post-trial assessment. Participants initially received twice-weekly 0.5 mg\/kg subcutaneous racemic ketamine (fixed regimen) for 4 weeks. Dosing was revised after a Data Safety Monitoring Board recommendation, to a \u2018flexible regimen\u2019 (0.5\u20130.9 mg\/kg with response-guided increments). Depression and safety outcomes were assessed throughout treatment, and 4 weeks and 6 months later.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125026106928_as4\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>130 RCT participants entered the OLE phase of whom 32 underwent the fixed OLE regimen and 98 the flexible regimen. At treatment end, 30% (36\/116) had responded (MADRS reduction \u226550%), and 4 weeks later 17% (19\/110) were \u2018responders\u2019. Over 50% experienced &lt;25% MADRS reduction. There was no difference in depression response at any time point between regimens. Those treated with ketamine during the RCT showed a transient reduced response after first OLE treatment but at no other assessment point. There were no reports of suicide or suicidal behaviour requiring admission and only expected side-effects observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125026106928_as5\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In a highly treatment-resistant sample, a 4-week course of subcutaneous racemic ketamine produced short-term clinical benefit in a minority of participants, with response rates declining substantially after treatment cessation, and no unexpected safety concerns. Exploratory subgroup analyses showed no association between prior RCT ketamine exposure and OLE outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125026106928_as6\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      ACTRN12616001096448 at\n                      <jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.anzctr.org.au\">www.anzctr.org.au<\/jats:uri>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1192\/bjp.2026.10692","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T06:48:21Z","timestamp":1783320501000},"page":"1-7","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":0,"title":["Effectiveness and safety of repeat dose subcutaneous ketamine for treatment-resistant depression, and the impact of prior ketamine treatment: open label extension of the KADS study"],"prefix":"10.1192","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0476-9146","authenticated-orcid":false,"given":"Nick","family":"Glozier","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0384j8v12","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Sydney"},{"id":[{"id":"https:\/\/ror.org\/04w6y2z35","id-type":"ROR","asserted-by":"publisher"}],"name":"Sydney Local Health District"},{"id":[{"id":"https:\/\/ror.org\/053mfxd72","id-type":"ROR","asserted-by":"publisher"}],"name":"ARC Centre of Excellence for Children and Families over the Life Course, University of Queensland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5018-1239","authenticated-orcid":false,"given":"Richard","family":"Morris","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0384j8v12","id-type":"ROR","asserted-by":"publisher"}],"name":"University of 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