{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T23:21:03Z","timestamp":1794352863809,"version":"4.9.0"},"reference-count":36,"publisher":"Cambridge University Press (CUP)","issue":"9","license":[{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Psychol. Med."],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"S0033291722000745_sec_a1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Antipsychotics are widely used in the treatment of major depressive disorder (MDD), but there has been no comprehensive meta-analytic assessment that examined their use as monotherapy and adjunctive therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291722000745_sec_a2\" sec-type=\"methods\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic review and a meta-analysis were conducted on randomized placebo-controlled trials (RCTs) that reported on the efficacy and safety\/tolerability of antipsychotics for the treatment of adults with MDD. Data of both monotherapy and adjunctive antipsychotic use were extracted, but analyzed separately using a random-effects model. Co-primary outcomes were study-defined-treatment response and intolerability-related discontinuation. We also illustrated the risk\/benefit balance of antipsychotics for MDD, using two-dimensional graphs representing the primary efficacy and safety\/tolerability outcome. Secondary outcomes included psychopathology, remission, all-cause-discontinuation, inefficacy-related discontinuation, and adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291722000745_sec_a3\" sec-type=\"results\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Forty-five RCTs with 12 724 patients were included in the analysis. In monotherapy (studies = 13,\n                      <jats:italic>n<\/jats:italic>\n                      = 4375), amisulpride [1.99 (1.55\u20132.55)], sulpiride [1.50 (1.03\u20132.17)], and quetiapine [1.48 (1.23\u20131.78)] were significantly superior to placebo regarding treatment response. However, intolerability-related discontinuations were significantly higher compared to placebo with amisulpride and quetiapine. In adjunctive therapy (studies = 32,\n                      <jats:italic>n<\/jats:italic>\n                      = 8349), ziprasidone [1.80 (1.07\u20133.04)], risperidone [1.59 (1.19\u20132.14)], aripiprazole [1.54 (1.35\u20131.76)], brexpiprazole [1.41 (1.21\u20131.66)], cariprazine [1.27 (1.07\u20131.52)], and quetiapine [1.23 (1.08\u20131.41)] were significantly superior to placebo regarding treatment response. However, of these antipsychotics that were superior to placebo, only risperidone was equivalent to placebo regarding discontinuation due to intolerability, while the other antipsychotics were inferior.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291722000745_sec_a4\" sec-type=\"conclusions\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Results suggest that there are significant differences regarding the risk\/benefit ratio among antipsychotics for MDD, which should inform clinical care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1017\/s0033291722000745","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T04:27:43Z","timestamp":1651724863000},"page":"4064-4082","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":44,"title":["Efficacy and safety\/tolerability of antipsychotics in the treatment of adult patients with major depressive disorder: a systematic review and meta-analysis"],"prefix":"10.1017","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0557-8648","authenticated-orcid":false,"given":"Taishiro","family":"Kishimoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiko","family":"Hagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunya","family":"Kurokawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Kane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph U.","family":"Correll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2022,5,5]]},"reference":[{"key":"S0033291722000745_ref27","doi-asserted-by":"publisher","DOI":"10.1080\/07448481.2018.1462819"},{"key":"S0033291722000745_ref11","doi-asserted-by":"publisher","DOI":"10.1080\/03007995.2018.1430220"},{"key":"S0033291722000745_ref1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.2082"},{"key":"S0033291722000745_ref10","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701561"},{"key":"S0033291722000745_ref29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.2010.02902.x"},{"key":"S0033291722000745_ref34","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.163.1.28"},{"key":"S0033291722000745_ref22","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v68n0602"},{"key":"S0033291722000745_ref30","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.14m09688"},{"key":"S0033291722000745_ref8","volume-title":"Mood disorders applied therapeutics: The clinical use of drugs","author":"Finley","year":"2009"},{"key":"S0033291722000745_ref28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001403"},{"key":"S0033291722000745_ref13","first-page":"Cd008121","article-title":"Second-generation antipsychotics for major depressive disorder and dysthymia","author":"Komossa","year":"2010","journal-title":"Cochrane Database Systematic Reviews"},{"key":"S0033291722000745_ref15","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31948-2"},{"key":"S0033291722000745_ref20","first-page":"3","article-title":"The role of dopamine and norepinephrine in depression and antidepressant treatment","volume":"67","author":"Nutt","year":"2006","journal-title":"Journal of Clinical Psychiatry"},{"key":"S0033291722000745_ref21","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001040"},{"key":"S0033291722000745_ref24","doi-asserted-by":"publisher","DOI":"10.1016\/S0095-4543(08)70003-4"},{"key":"S0033291722000745_ref33","doi-asserted-by":"publisher","DOI":"10.2174\/138945006775515464"},{"key":"S0033291722000745_ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2016.07.003"},{"key":"S0033291722000745_ref26","doi-asserted-by":"publisher","DOI":"10.1007\/BF02245606"},{"key":"S0033291722000745_ref32","unstructured":"The Cochrane Collaboration. Cochrane handbook for systematic reviews of interventions (Version 5.1.0). (2011). Retrieved August 31, 2019, from http:\/\/handbook.cochrane.org."},{"key":"S0033291722000745_ref35","unstructured":"WHO (2018) Depression: Fact sheet. Geneva: World Health Organisation. Retrieved August 12, 2019, from http:\/\/www.who.int\/mediacentre\/factsheets\/fs369\/en\/."},{"key":"S0033291722000745_ref6","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(86)90046-2"},{"key":"S0033291722000745_ref36","unstructured":"GBD (2017) Disease and Injury Incidence and Prevalence Collaborators, (2018). A systematic analysis for the Global Burden of Disease Study 2017. The Lancet, 392, 1789\u2013858."},{"key":"S0033291722000745_ref16","unstructured":"Methodology, WHO Collaborating Centre for Drug Statistics (Dec 16th 2019). ATC\/DDD index. Retrieved February 2nd, 2020, from https:\/\/www.whocc.no\/atc_ddd_index\/?code=N05A&showdescription=no."},{"key":"S0033291722000745_ref25","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.2018.27"},{"key":"S0033291722000745_ref4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32802-7"},{"key":"S0033291722000745_ref31","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.14m09689"},{"key":"S0033291722000745_ref17","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b2535"},{"key":"S0033291722000745_ref7","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.315.7109.629"},{"key":"S0033291722000745_ref9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1986.tb00071.x"},{"key":"S0033291722000745_ref5","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v63n1102"},{"key":"S0033291722000745_ref12","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.23.3095"},{"key":"S0033291722000745_ref18","doi-asserted-by":"publisher","DOI":"10.1097\/YIC.0b013e3282f2b3cb"},{"key":"S0033291722000745_ref19","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2009.09030312"},{"key":"S0033291722000745_ref2","first-page":"30","article-title":"Potential mechanisms of action of atypical antipsychotic medications in treatment-resistant depression and anxiety","volume":"66","author":"Blier","year":"2005","journal-title":"Journal of Clinical Psychiatry"},{"key":"S0033291722000745_ref14","doi-asserted-by":"publisher","DOI":"10.1002\/da.20740"},{"key":"S0033291722000745_ref3","doi-asserted-by":"publisher","DOI":"10.1177\/106002809502900210"}],"container-title":["Psychological Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0033291722000745","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T22:14:02Z","timestamp":1689891242000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0033291722000745\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,5]]},"references-count":36,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["S0033291722000745"],"URL":"https:\/\/doi.org\/10.1017\/s0033291722000745","relation":{},"ISSN":["0033-2917","1469-8978"],"issn-type":[{"value":"0033-2917","type":"print"},{"value":"1469-8978","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,5]]},"assertion":[{"value":"Copyright \u00a9 The Author(s), 2022. Published by Cambridge University Press","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 (http:\/\/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"}]}}