{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:41:27Z","timestamp":1792078887211,"version":"4.4.0"},"reference-count":40,"publisher":"Royal College of Psychiatrists","issue":"5","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"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"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec id=\"S0007125025001254_as1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Older adults with treatment-resistant depression (TRD) benefit more from treatment augmentation than switching. It is useful to identify moderators that influence these treatment strategies for personalised medicine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125025001254_as2\">\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Our objective was to test whether age, executive dysfunction, comorbid medical burden, comorbid anxiety or the number of previous adequate antidepressant trials could moderate the superiority of augmentation over switching. A significant moderator would influence the differential effect of augmentation versus switching on treatment outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125025001254_as3\">\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      We performed a preplanned moderation analysis of data from the Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM) randomised controlled trial (\n                      <jats:italic>N<\/jats:italic>\n                      = 742). Participants were 60 years old or older with TRD. Participants were either (a) randomised to antidepressant augmentation with aripiprazole (2.5\u201315 mg), bupropion (150\u2013450 mg) or lithium (target serum drug level 0.6 mmol\/L) or (b) switched to bupropion (150\u2013450 mg) or nortriptyline (target serum drug level 80\u2013120 ng\/mL). Treatment duration was 10 weeks. The two main outcomes of this analysis were (a) symptom improvement, defined as change in Montgomery\u2013Asberg Depression Rating Scale (MADRS) scores from baseline to week 10 and (b) remission, defined as MADRS score of 10 or less at week 10.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125025001254_as4\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 742 participants, 480 were randomised to augmentation and 262 to switching. The number of adequate previous antidepressant trials was a significant moderator of depression symptom improvement (\n                      <jats:italic>b<\/jats:italic>\n                      = \u22121.6,\n                      <jats:italic>t<\/jats:italic>\n                      = \u22122.1,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.033, 95% CI [\u22123.0, \u22120.1], where\n                      <jats:italic>b<\/jats:italic>\n                      is the coefficient of the relationship (i.e. effect size), and\n                      <jats:italic>t<\/jats:italic>\n                      is the\n                      <jats:italic>t<\/jats:italic>\n                      -statistic for that coefficient associated with the\n                      <jats:italic>P<\/jats:italic>\n                      -value). The effect was similar across all augmentation strategies. No other putative moderators were significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125025001254_as5\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Augmenting was superior to switching antidepressants only in older patients with fewer than three previous antidepressant trials. This suggests that other intervention strategies should be considered following three or more trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1192\/bjp.2025.125","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T03:39:32Z","timestamp":1750304372000},"page":"790-797","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":3,"title":["Moderators of antidepressant augmentation versus switch in the OPTIMUM randomised controlled trial"],"prefix":"10.1192","volume":"227","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6578-2109","authenticated-orcid":false,"given":"Helena K.","family":"Kim","sequence":"first","affiliation":[{"name":"University of Toronto, Toronto"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan F.","family":"Karp","sequence":"additional","affiliation":[{"name":"University of Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Lavretsky","sequence":"additional","affiliation":[{"name":"University of California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8422-5818","authenticated-orcid":false,"given":"Daniel M.","family":"Blumberger","sequence":"additional","affiliation":[{"name":"University of Toronto, Toronto"},{"name":"Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J.","family":"Brown","sequence":"additional","affiliation":[{"name":"New York State Psychiatric Institute, Columbia University Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6806-0235","authenticated-orcid":false,"given":"Alastair J.","family":"Flint","sequence":"additional","affiliation":[{"name":"University of Toronto, Toronto"},{"name":"University Health Network"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Lenard","sequence":"additional","affiliation":[{"name":"Washington University in St Louis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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Published by Cambridge University Press on behalf of Royal College of Psychiatrists","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https:\/\/creativecommons.org\/licenses\/by\/4.0\/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}