{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:24:54Z","timestamp":1794007494972,"version":"4.8.0"},"reference-count":47,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T00:00:00Z","timestamp":1658361600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019418","name":"NIHR Maudsley Biomedical Research Centre","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/100019418","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Major depressive disorder (MDD) is a highly burdensome health condition, for which there are numerous accepted pharmacological and psychological interventions. Adjunctive treatment (augmentation\/combination) is recommended for the ~50% of MDD patients who do not adequately respond to first-line treatment. We aimed to evaluate the current evidence for concomitant approaches for people with early-stage treatment-resistant depression (TRD; defined below).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We systematically searched Medline and Institute for Scientific Information Web of Science to identify randomised controlled trials of adjunctive treatment of \u2a7e10 adults with MDD who had not responded to \u2a7e1 adequate antidepressant. The cochrane risk of bias (RoB) tool was used to assess study quality. Pre-post treatment meta-analyses were performed, allowing for comparison across heterogeneous study designs independent of comparator interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>In total, 115 trials investigating 48 treatments were synthesised. The mean intervention duration was 9\u2009weeks (range 5\u2009days to 18\u2009months) with most studies assessed to have low ( n\u2009=\u200957) or moderate ( n\u2009=\u200951) RoB. The highest effect sizes (ESs) were from cognitive behavioural therapy (ES\u2009=\u20091.58, 95% confidence interval (CI): 1.09\u20132.07), (es)ketamine (ES\u2009=\u20091.48, 95% CI: 1.23\u20131.73) and risperidone (ES\u2009=\u20091.42, 95% CI: 1.29\u20131.61). Only aripiprazole and lithium were examined in \u2a7e10 studies. Pill placebo (ES\u2009=\u20090.89, 95% CI: 0.81\u20130.98) had a not inconsiderable ES, and only six treatments\u2019 95% CIs did not overlap with pill placebo\u2019s (aripiprazole, (es)ketamine, mirtazapine, olanzapine, quetiapine and risperidone). We report marked heterogeneity between studies for almost all analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our findings support cautious optimism for several augmentation strategies; although considering the high prevalence of TRD, evidence remains inadequate for each treatment option.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/02698811221104058","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T06:38:53Z","timestamp":1658385533000},"page":"268-278","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":73,"title":["Systematic review and meta-analysis of augmentation and combination treatments for early-stage treatment-resistant depression"],"prefix":"10.1177","volume":"37","author":[{"given":"Fraser","family":"Scott","sequence":"first","affiliation":[{"name":"South London and Maudsley NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot","family":"Hampsey","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Gnanapragasam","sequence":"additional","affiliation":[{"name":"South London and Maudsley NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5818-2199","authenticated-orcid":false,"given":"Lindsey","family":"Marwood","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6471-537X","authenticated-orcid":false,"given":"Rachael W","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cansu","family":"Emre","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lora","family":"Korotkova","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonatan","family":"Mart\u00edn-Dombrowski","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J","family":"Cleare","sequence":"additional","affiliation":[{"name":"South London and Maudsley NHS Foundation Trust, London, UK"},{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan H","family":"Young","sequence":"additional","affiliation":[{"name":"South London and Maudsley NHS Foundation Trust, London, UK"},{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2984-1124","authenticated-orcid":false,"given":"Rebecca","family":"Strawbridge","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,7,21]]},"reference":[{"key":"bibr1-02698811221104058","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2019.11.028"},{"key":"bibr2-02698811221104058","volume-title":"Diagnostic and Statistical Manual of Mental Disorders","author":"American Psychiatric 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(2022) Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins JPT, Thomas J, Chandler J, et al. (eds). Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022). 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