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A literature search of PubMed, Cochrane Library, and Embase from inception until April 13th, 2023 identified randomized, controlled trials (RCTs) of adults with depression who had not responded to at least two antidepressant trials; all RCTs had \u226510 participants per study arm, and participants with bipolar or psychotic depression were excluded. The Cochrane Risk of Bias Tool-2 was used to assess study quality. Response rate was the primary outcome measure. Odds ratios (ORs) using a random effects NMA are reported. From 8234 records, 69 RCTs were included in this analysis, encompassing 10,285 participants (5662\u2009F\/4623\u2009M) and 25 separate treatments. Six of the 25 treatments demonstrated a higher response rate versus placebo or sham treatment: electroconvulsive therapy (ECT), minocycline, theta-burst stimulation (TBS), repetitive transcranial magnetic stimulation (rTMS), ketamine, and aripiprazole. ORs ranged from 1.9 (95%CI\u2009=\u2009[1.25; 2.91]) for aripiprazole to 12.86 (95%CI\u2009=\u2009[4.07; 40.63]) for ECT. Moderate heterogeneity of the model was observed (I\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u200947.3% (95%CI [26.8\u201362%]). Of the included studies, 12.5% were rated as having high risk of bias, 28.13% as having low risk, and 59.38% as showing some concerns. Several effective treatments for TRD showed robust treatment effects across outcomes (ECT, TBS, rTMS, and ketamine), and others showed promising results for some, but not all, outcomes (minocycline, aripiprazole). These findings may help guide evidence-based treatment choices for TRD. Study Registration: PROSPERO (#CRD42023420584).\n                  <\/jats:p>","DOI":"10.1038\/s41386-024-02044-5","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T07:23:46Z","timestamp":1735543426000},"page":"913-919","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Relative effectiveness of antidepressant treatments in treatment-resistant depression: a systematic review and network meta-analysis of randomized controlled trials"],"prefix":"10.1038","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5556-1808","authenticated-orcid":false,"given":"Johan","family":"Saelens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Gramser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7252-7130","authenticated-orcid":false,"given":"Victoria","family":"Watzal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4442-7412","authenticated-orcid":false,"suffix":"Jr.","given":"Carlos A.","family":"Zarate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4641-9539","authenticated-orcid":false,"given":"Rupert","family":"Lanzenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7144-2282","authenticated-orcid":false,"given":"Christoph","family":"Kraus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"2044_CR1","unstructured":"European Medicines Agency. 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Dr. Lanzenberger received investigator-initiated research funding from Siemens Healthcare regarding clinical research using PET\/MR and travel grants and\/or conference speaker honoraria from Janssen-Cilag Pharma GmbH in 2023, and Bruker BioSpin, Shire, AstraZeneca, Lundbeck A\/S, Dr. Willmar Schwabe GmbH, Orphan Pharmaceuticals AG, Janssen-Cilag Pharma GmbH, Heel and Roche Austria GmbH., and Janssen-Cilag Pharma GmbH in the years before 2020. He is a shareholder of the start-up company BM Health GmbH, Austria since 2019. Dr. Zarate is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; as a co-inventor on a patent for the use of (2\u2009\n                      R\n                      ,6\u2009\n                      R\n                      )-hydroxynorketamine, (\n                      S\n                      )-dehydronorketamine, and other stereoisomeric dehydroxylated and hydroxylated metabolites of (\n                      R,S\n                      )-ketamine metabolites in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of (2\u2009\n                      R\n                      ,6\u2009\n                      R\n                      )-hydroxynorketamine and (2\n                      S\n                      ,6\n                      S\n                      )-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders. He has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. All other authors have no conflict of interest to disclose, financial or otherwise.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}