{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:50:26Z","timestamp":1790297426880,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,2,26]],"date-time":"2023-02-26T00:00:00Z","timestamp":1677369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>This phase 3, randomized, double\u2010blind, placebo\u2010controlled study (NCT02600507) evaluated the efficacy and safety of lumateperone adjunctive therapy to lithium or valproate in patients with bipolar depression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients (18\u201375\u2009years) with bipolar I or bipolar II disorder experiencing a major depressive episode (MDE), with inadequate therapeutic response to lithium or valproate, were randomized 1:1:1 to 6\u2009weeks adjunctive therapy with lumateperone 28\u2009mg (<jats:italic>n<\/jats:italic>\u00a0=\u2009176), lumateperone 42\u2009mg (<jats:italic>n<\/jats:italic>\u00a0=\u2009177), or placebo (<jats:italic>n<\/jats:italic>\u00a0=\u2009176). The primary and key secondary efficacy endpoints were change from baseline to Day 43 in Montgomery\u2010\u00c5sberg Depression Rating Scale (MADRS) Total score and the Clinical Global Impression Scale\u2010Bipolar Version\u2010Severity Scale (CGI\u2010BP\u2010S) depression subscore. Safety assessments included adverse events, laboratory evaluations, vital signs, extrapyramidal symptoms (EPS), and suicidality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients treated with adjunctive lumateperone 42\u2009mg showed significantly greater improvement compared with adjunctive placebo in MADRS Total score (LS mean difference vs placebo [LSMD], \u22122.4; <jats:italic>p\u2009=<\/jats:italic>\u00a00.02) and CGI\u2010BP\u2010S depression subscore (LSMD, \u22120.3; <jats:italic>p\u2009=<\/jats:italic>\u00a00.01), while adjunctive lumateperone 28\u2009mg showed numerical improvement in MADRS Total score (LSMD, \u22121.7; <jats:italic>p\u2009=<\/jats:italic>\u00a00.10) and improvement in the CGI\u2010BP\u2010S depression subscore (LSMD, \u22120.3; <jats:italic>p\u2009=<\/jats:italic>\u00a00.04). Adjunctive lumateperone treatment was well tolerated; treatment\u2010emergent adverse events reported at rates &gt;5% and twice placebo for lumateperone 42\u2009mg were somnolence (11.3%), dizziness (10.7%), and nausea (8.5%), with minimal risk of EPS, metabolic abnormalities, or increased prolactin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Lumateperone 42\u2010mg treatment adjunctive to lithium or valproate significantly improved depression symptoms and was generally well tolerated in patients with MDEs associated with either bipolar I or bipolar II disorder.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.13310","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T08:35:23Z","timestamp":1676277323000},"page":"478-488","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Adjunctive lumateperone (<scp>ITI<\/scp>\u2010007) in the treatment of bipolar depression: Results from a randomized <scp>placebo\u2010controlled<\/scp> clinical trial"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4560-6180","authenticated-orcid":false,"given":"Trisha","family":"Suppes","sequence":"first","affiliation":[{"name":"Stanford University School of Medicine  Stanford California USA"},{"name":"US Department of Veterans Affairs Palo Alto Healthcare System  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Durgam","sequence":"additional","affiliation":[{"name":"Intra\u2010Cellular Therapies, Inc  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan G.","family":"Kozauer","sequence":"additional","affiliation":[{"name":"Intra\u2010Cellular Therapies, Inc  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Chen","sequence":"additional","affiliation":[{"name":"Intra\u2010Cellular Therapies, Inc  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan D.","family":"Lakkis","sequence":"additional","affiliation":[{"name":"Intra\u2010Cellular Therapies, Inc  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E.","family":"Davis","sequence":"additional","affiliation":[{"name":"Intra\u2010Cellular Therapies, Inc  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Satlin","sequence":"additional","affiliation":[{"name":"Intra\u2010Cellular Therapies, Inc  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly E.","family":"Vanover","sequence":"additional","affiliation":[{"name":"Intra\u2010Cellular Therapies, Inc  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Mates","sequence":"additional","affiliation":[{"name":"Intra\u2010Cellular Therapies, Inc  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4733-2523","authenticated-orcid":false,"given":"Roger S.","family":"McIntyre","sequence":"additional","affiliation":[{"name":"Mood Disorders Psychopharmacology Unit University Health Network, University of Toronto  Toronto Ontario Canada"},{"name":"Institute of Medical Science University of Toronto  Toronto Ontario Canada"},{"name":"Department of Psychiatry University of Toronto  Toronto Ontario Canada"},{"name":"Department of Pharmacology University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8049-4351","authenticated-orcid":false,"given":"Mauricio","family":"Tohen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry &amp; 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