{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:27:43Z","timestamp":1793413663699,"version":"4.5.0"},"reference-count":82,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:sec id=\"ab-yoi260019-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Most adults living with major depressive disorder (MDD) fail to achieve remission with conventional antidepressants. The US Food and Drug Administration (FDA) has approved 5 atypical antipsychotics in MDD on the basis of their substantial evidence of efficacy and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-yoi260019-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To compare the efficacy and acceptability of FDA-approved atypical antipsychotics for the adjunctive treatment of MDD in order to provide decision support to practitioners and persons with lived experience.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-yoi260019-6\">\n                    <jats:title>Data Sources<\/jats:title>\n                    <jats:p>A systematic search was conducted using PubMed\/MEDLINE, PsycINFO, the Cochrane Library, and Embase from database inception through July 15, 2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-yoi260019-7\">\n                    <jats:title>Study Selection<\/jats:title>\n                    <jats:p>Six independent raters screened publications for eligibility. Inclusion criteria were atypical antipsychotics that are FDA approved in the adjunctive treatment of MDD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-yoi260019-8\">\n                    <jats:title>Data Extraction and Synthesis<\/jats:title>\n                    <jats:p>Two independent raters obtained data and examined risk of bias in accordance with the Cochrane criteria. Effect sizes were synthesized using random-effects models. Data were analyzed from August to September 2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-yoi260019-9\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>The primary outcomes were efficacy (ie, \u226550% reduction from baseline in the total Montgomery-\u00c5sberg Depression Rating Scale [MADRS] score) and acceptability (ie, all-cause discontinuation).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-yoi260019-10\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 22 short-term studies comprising 10\u202f962 participants (aripiprazole: n\u2009=\u20091297; brexpiprazole: n\u2009=\u20091973; cariprazine: n\u2009=\u20091894; lumateperone: n\u2009=\u2009483; quetiapine extended release [XR]: n\u2009=\u2009719; and placebo: n\u2009=\u20094596) were included for analysis. Lumateperone had the highest effect size for efficacy (risk ratio [RR], 1.72; 95% credible interval [CrI], 1.40-2.15), followed by aripiprazole (RR, 1.53; 95% CrI, 1.32-1.77), brexpiprazole (RR, 1.38; 95% CrI, 1.18-1.65), cariprazine (RR, 1.20; 95% CrI, 1.07-1.36), and quetiapine XR (RR, 1.15; 95% CrI, 0.96-1.35). A hierarchy of acceptability was observed, with aripiprazole exhibiting the highest acceptability (RR, 1.16; 95% CrI, 0.89-1.50), followed by cariprazine (RR, 1.44; 95% CrI, 1.15-1.82), brexpiprazole (RR, 1.47; 95% CrI, 1.18-1.85), quetiapine XR (RR, 1.56; 95% CrI, 1.14-2.12), and lumateperone (RR, 2.30; 95% CrI, 1.45-3.84). Secondary outcomes (eg, symptomatic remission) and exploratory outcomes (eg, clinically significant weight gain) accorded with the coprimary outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-yoi260019-11\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>This systematic review and meta-analysis indicates that differences exist between adjunctive atypical antipsychotics in the treatment of MDD with respect to overall efficacy and acceptability, which should be simultaneously considered. The absence of adequate and well-controlled studies documenting maintenance efficacy of adjunctive atypical antipsychotics in MDD remains a knowledge gap.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2026.0658","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T15:31:22Z","timestamp":1778081482000},"page":"741","source":"Crossref","is-referenced-by-count":11,"title":["Adjunctive Antipsychotics in Major Depressive Disorder"],"prefix":"10.1001","volume":"83","author":[{"given":"Roger S.","family":"McIntyre","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada"},{"name":"Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada"},{"name":"Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Stahl","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuroscience, University of California, Riverside"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Ryul","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, College of Medicine, Konyang University, Daejeon, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Pompili","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Mental Health, and Sensory Organs, Sant\u2019Andrea Hospital, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph F.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph U.","family":"Correll","sequence":"additional","affiliation":[{"name":"Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Hempstead, New York"},{"name":"Department of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra\/Northwell, Hempstead, New York"},{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela T. H.","family":"Kwan","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, German Center for Mental Health, partner site Berlin, Berlin, Germany"},{"name":"Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine E.","family":"Dri","sequence":"additional","affiliation":[{"name":"Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada"},{"name":"Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maj","family":"Vinberg","sequence":"additional","affiliation":[{"name":"The Early Multimodular Prevention and Intervention Research Institution, Psychiatric 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