{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T20:13:39Z","timestamp":1778012019799,"version":"3.51.4"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"vor","delay-in-days":120,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Otsuka Pharmaceutical Development & Commercialization Inc"},{"DOI":"10.13039\/501100013327","name":"H. Lundbeck A\/S","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013327","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The successful treatment of schizophrenia entails improvement across a spectrum of symptoms. The aim of this post hoc analysis was to characterize the short- and long-term effects of brexpiprazole on Positive and Negative Syndrome Scale (PANSS) \u2018Marder factors.\u2019 Data were included from three 6-week, randomized, double-blind, placebo-controlled studies; a 52-week, randomized, double-blind, placebo-controlled maintenance treatment study; and two 52-week open-label extension (OLEx) studies\u2014all in schizophrenia (DSM-IV-TR criteria). Patients receiving oral brexpiprazole were dosed at 2\u20134 mg\/day (short-term studies) or 1\u20134 mg\/day (long-term studies). At Week 6, least squares mean differences (LSMDs, with 95% confidence limits [CLs]) for brexpiprazole (n = 868) vs placebo (n = 517) were: Positive symptoms: \u22121.55 (\u22122.30, \u22120.80), P &amp;lt; .0001, Cohen\u2019s d effect size (ES) = 0.27; Negative symptoms: \u22121.12 (\u22121.63, \u22120.61), P &amp;lt; .0001, ES = 0.29; Disorganized thought: \u22121.26 (\u22121.78, \u22120.74), P &amp;lt; .0001, ES = 0.32; Uncontrolled hostility\/excitement: \u22120.76 (\u22121.15, \u22120.37), P = .0002, ES = 0.26; Anxiety\/ depression: \u22120.56 (\u22120.91, \u22120.22), P = .0014, ES = 0.22. At last visit of the maintenance study, LSMDs (95% CLs) for brexpiprazole (n = 96) vs placebo (n = 104) were: Positive symptoms: \u22123.44 (\u22124.99, \u22121.89), P &amp;lt; .0001, ES = 0.62; Negative symptoms: \u22121.23 (\u22122.52, 0.07), P = .063, ES = 0.27; Disorganized thought: \u22121.69 (\u22122.81, \u22120.56), P = .0035, ES = 0.42; Uncontrolled hostility\/excitement: \u22121.26 (\u22122.12, \u22120.39), P = .0046, ES = 0.41; Anxiety\/depression: \u22120.72 (\u22121.47, 0.03), P = .061, ES = 0.27. In the OLEx studies, improvements were maintained over 58 (6 + 52) weeks of brexpiprazole treatment. In conclusion, these data suggest that brexpiprazole treats the continuum of schizophrenia symptoms, in the short- and long-term. Trial Registration: Data used in this post hoc analysis came from ClinicalTrials.gov identifiers: NCT01396421, NCT01393613, NCT01810380, NCT01668797, NCT01397786, NCT01810783.<\/jats:p>","DOI":"10.1093\/schizbullopen\/sgab014","type":"journal-article","created":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T15:40:04Z","timestamp":1619624404000},"source":"Crossref","is-referenced-by-count":9,"title":["Effects of Brexpiprazole Across Symptom Domains in Patients With Schizophrenia: <i>Post Hoc<\/i> Analysis of Short- and Long-Term Studies"],"prefix":"10.1093","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0288-309X","authenticated-orcid":false,"given":"Stephen R","family":"Marder","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Semel Institute for Neuroscience at UCLA and the VA VISN 22 Mental Illness Research, Education, and Clinical Center, Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stine R","family":"Meehan","sequence":"additional","affiliation":[{"name":"H. Lundbeck A\/S, Valby, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Weiss","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development & Commercialization Inc, Princeton, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalei","family":"Chen","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development & Commercialization Inc, Princeton, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Hobart","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development & Commercialization Inc, Princeton, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nanco","family":"Hefting","sequence":"additional","affiliation":[{"name":"H. Lundbeck A\/S, Valby, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,5,1]]},"reference":[{"key":"2021070810581345600_CIT0001","doi-asserted-by":"crossref","DOI":"10.1176\/appi.books.9780890425596","volume-title":"Diagnostic and Statistical Manual of Mental Disorders","author":"American Psychiatric Association","year":"2013","edition":"5"},{"issue":"10039","key":"2021070810581345600_CIT0002","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/S0140-6736(15)01121-6","article-title":"Schizophrenia","volume":"388","author":"Owen","year":"2016","journal-title":"Lancet."},{"issue":"2-3","key":"2021070810581345600_CIT0003","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.schres.2013.07.014","article-title":"Association of prominent positive and prominent negative symptoms and functional health, well-being, healthcare-related quality of life and family burden: a CATIE analysis","volume":"150","author":"Rabinowitz","year":"2013","journal-title":"Schizophr Res."},{"issue":"2","key":"2021070810581345600_CIT0004","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.wpsyc.2012.05.004","article-title":"Predicting the severity of everyday functional disability in people with schizophrenia: cognitive deficits, functional capacity, symptoms, and health status","volume":"11","author":"Harvey","year":"2012","journal-title":"World Psychiatry."},{"issue":"1-3","key":"2021070810581345600_CIT0005","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.schres.2006.09.027","article-title":"The burden of depressive symptoms in the long-term treatment of patients with schizophrenia","volume":"90","author":"Conley","year":"2007","journal-title":"Schizophr Res."},{"issue":"10202","key":"2021070810581345600_CIT0006","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/S0140-6736(19)31135-3","article-title":"Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis","volume":"394","author":"Huhn","year":"2019","journal-title":"Lancet."},{"issue":"2","key":"2021070810581345600_CIT0007","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1093\/schbul\/13.2.261","article-title":"The Positive and Negative Syndrome Scale (PANSS) for schizophrenia","volume":"13","author":"Kay","year":"1987","journal-title":"Schizophr Bull."},{"issue":"12","key":"2021070810581345600_CIT0008","doi-asserted-by":"crossref","first-page":"538","DOI":"10.4088\/JCP.v58n1205","article-title":"The effects of risperidone on the five dimensions of schizophrenia derived by factor analysis: combined results of the North American trials","volume":"58","author":"Marder","year":"1997","journal-title":"J Clin Psychiatry."},{"issue":"4","key":"2021070810581345600_CIT0009","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/BF02354306","article-title":"A new five factor model of schizophrenia","volume":"65","author":"Lindenmayer","year":"1994","journal-title":"Psychiatr Q."},{"issue":"4","key":"2021070810581345600_CIT0010","doi-asserted-by":"crossref","first-page":"551","DOI":"10.4088\/JCP.v65n0416","article-title":"Effects of atypical antipsychotics on the syndromal profile in treatment-resistant schizophrenia","volume":"65","author":"Lindenmayer","year":"2004","journal-title":"J Clin Psychiatry."},{"issue":"1-3","key":"2021070810581345600_CIT0011","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.schres.2012.01.031","article-title":"Searching for a consensus five-factor model of the Positive and Negative Syndrome Scale for schizophrenia","volume":"137","author":"Wallwork","year":"2012","journal-title":"Schizophr Res."},{"issue":"3","key":"2021070810581345600_CIT0012","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1124\/jpet.114.213793","article-title":"Brexpiprazole I: in vitro and in vivo characterization of a novel serotonin-dopamine activity modulator","volume":"350","author":"Maeda","year":"2014","journal-title":"J Pharmacol Exp Ther."},{"issue":"9","key":"2021070810581345600_CIT0013","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1176\/appi.ajp.2015.14101275","article-title":"Efficacy and safety of brexpiprazole for the treatment of acute schizophrenia: A 6-week randomized, double-blind, placebo-controlled trial","volume":"172","author":"Correll","year":"2015","journal-title":"Am J Psychiatry."},{"issue":"1-3","key":"2021070810581345600_CIT0014","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.schres.2015.01.038","article-title":"A multicenter, randomized, double-blind, controlled phase 3 trial of fixed-dose brexpiprazole for the treatment of adults with acute schizophrenia","volume":"164","author":"Kane","year":"2015","journal-title":"Schizophr Res."},{"issue":"5","key":"2021070810581345600_CIT0015","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1017\/neu.2016.57","article-title":"Brexpiprazole in patients with schizophrenia: overview of short- and long-term phase 3 controlled studies","volume":"29","author":"Marder","year":"2017","journal-title":"Acta Neuropsychiatr."},{"issue":"3","key":"2021070810581345600_CIT0016","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1017\/neu.2020.8","article-title":"Post hoc analysis of a randomised, placebo-controlled, active-reference 6-week study of brexpiprazole in acute schizophrenia","volume":"32","author":"Marder","year":"2020","journal-title":"Acta Neuropsychiatr"},{"issue":"1","key":"2021070810581345600_CIT0017","first-page":"11","article-title":"Efficacy and safety of brexpiprazole (OPC-34712) as maintenance treatment in adults with schizophrenia: a randomized, double-blind, placebo-controlled study","volume":"20","author":"Fleischhacker","year":"2017","journal-title":"Int J Neuropsychopharmacol."},{"issue":"5","key":"2021070810581345600_CIT0018","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1093\/ijnp\/pyy002","article-title":"A long-term, open-label study to evaluate the safety and tolerability of brexpiprazole as maintenance treatment in adults with schizophrenia","volume":"21","author":"Forbes","year":"2018","journal-title":"Int J Neuropsychopharmacol."},{"key":"2021070810581345600_CIT0019","volume-title":"Diagnostic and Statistical Manual of Mental Disorders","author":"American Psychiatric Association","year":"2000","edition":"4"},{"issue":"3","key":"2021070810581345600_CIT0020","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0920-9964(99)00129-2","article-title":"Stability of the five-factor structure of the Positive and Negative Syndrome Scale (PANSS)","volume":"42","author":"Lan\u00e7on","year":"2000","journal-title":"Schizophr Res."},{"key":"2021070810581345600_CIT0021","volume-title":"Statistical Power Analysis for the Behavioral Sciences","author":"Cohen","year":"1988","edition":"2"},{"issue":"4","key":"2021070810581345600_CIT0022","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1017\/S1461145703003651","article-title":"Efficacy and safety of aripiprazole vs. haloperidol for long-term maintenance treatment following acute relapse of schizophrenia","volume":"6","author":"Kasper","year":"2003","journal-title":"Int J Neuropsychopharmacol."},{"issue":"1","key":"2021070810581345600_CIT0023","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1017\/S1092852917000220","article-title":"Evaluation of the long-term safety and tolerability of cariprazine in patients with schizophrenia: results from a 1-year open-label study","volume":"23","author":"Cutler","year":"2018","journal-title":"CNS Spectr."},{"issue":"1","key":"2021070810581345600_CIT0024","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4088\/JCP.08m04310","article-title":"The acute efficacy of aripiprazole across the symptom spectrum of schizophrenia: a pooled post hoc analysis from 5 short-term studies","volume":"70","author":"Janicak","year":"2009","journal-title":"J Clin Psychiatry."},{"issue":"1","key":"2021070810581345600_CIT0025","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.euroneuro.2018.10.008","article-title":"Efficacy of cariprazine across symptom domains in patients with acute exacerbation of schizophrenia: Pooled analyses from 3 Phase II\/III studies","volume":"29","author":"Marder","year":"2019","journal-title":"Eur Neuropsychopharmacol."},{"issue":"1-3","key":"2021070810581345600_CIT0026","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.schres.2011.05.018","article-title":"Efficacy of iloperidone in schizophrenia: a PANSS five-factor analysis","volume":"131","author":"Citrome","year":"2011","journal-title":"Schizophr Res."},{"issue":"1","key":"2021070810581345600_CIT0027","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.eurpsy.2014.08.001","article-title":"Efficacy of lurasidone across five symptom dimensions of schizophrenia: pooled analysis of short-term, placebo-controlled studies","volume":"30","author":"Loebel","year":"2015","journal-title":"Eur Psychiatry."},{"issue":"10","key":"2021070810581345600_CIT0028","doi-asserted-by":"crossref","first-page":"757","DOI":"10.4088\/JCP.v62n1003","article-title":"The effects of olanzapine on the 5 dimensions of schizophrenia derived by factor analysis: combined results of the North American and international trials","volume":"62","author":"Davis","year":"2001","journal-title":"J Clin Psychiatry."},{"key":"2021070810581345600_CIT0029","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.eurpsy.2019.01.015","article-title":"The efficacy of cariprazine in negative symptoms of schizophrenia: Post hoc analyses of PANSS individual items and PANSS-derived factors","volume":"58","author":"Fleischhacker","year":"2019","journal-title":"Eur Psychiatry."},{"issue":"10074","key":"2021070810581345600_CIT0030","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/S0140-6736(17)30060-0","article-title":"Cariprazine versus risperidone monotherapy for treatment of predominant negative symptoms in patients with schizophrenia: a randomised, double-blind, controlled trial","volume":"389","author":"N\u00e9meth","year":"2017","journal-title":"Lancet."},{"issue":"1","key":"2021070810581345600_CIT0031","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/PRA.0000000000000117","article-title":"A flexible-dose study of paliperidone ER in patients with nonacute schizophrenia previously treated unsuccessfully with oral olanzapine","volume":"22","author":"Kotler","year":"2016","journal-title":"J Psychiatr Pract."},{"issue":"1","key":"2021070810581345600_CIT0032","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.comppsych.2010.12.003","article-title":"Factors associated with adherence to treatment with olanzapine and other atypical antipsychotic medications in patients with schizophrenia","volume":"53","author":"Liu-Seifert","year":"2012","journal-title":"Compr Psychiatry."},{"issue":"2-3","key":"2021070810581345600_CIT0033","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.schres.2013.08.024","article-title":"Long-term effects of asenapine or olanzapine in patients with persistent negative symptoms of schizophrenia: a pooled analysis","volume":"150","author":"Potkin","year":"2013","journal-title":"Schizophr Res."},{"key":"2021070810581345600_CIT0034","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1471-244X-12-20","article-title":"A patient perspective of the impact of medication side effects on adherence: results of a cross-sectional nationwide survey of patients with schizophrenia","volume":"12","author":"DiBonaventura","year":"2012","journal-title":"BMC Psychiatry."},{"key":"2021070810581345600_CIT0035","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s12991-020-00292-5","article-title":"The impact on functioning of second-generation antipsychotic medication side effects for patients with schizophrenia: a worldwide, cross-sectional, web-based survey","volume":"19","author":"Tandon","year":"2020","journal-title":"Ann Gen Psychiatry."},{"issue":"1-3","key":"2021070810581345600_CIT0036","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.schres.2016.04.013","article-title":"Overview of short- and long-term tolerability and safety of brexpiprazole in patients with schizophrenia","volume":"174","author":"Kane","year":"2016","journal-title":"Schizophr Res."}],"container-title":["Schizophrenia Bulletin Open"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/schizbullopen\/advance-article-pdf\/doi\/10.1093\/schizbullopen\/sgab014\/37745339\/sgab014.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/schizbullopen\/article-pdf\/2\/1\/sgab014\/38606707\/sgab014.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/schizbullopen\/article-pdf\/2\/1\/sgab014\/38606707\/sgab014.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T19:37:26Z","timestamp":1625773046000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/schizbullopen\/article\/doi\/10.1093\/schizbullopen\/sgab014\/6261428"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,1]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1,1]]}},"URL":"https:\/\/doi.org\/10.1093\/schizbullopen\/sgab014","relation":{},"ISSN":["2632-7899"],"issn-type":[{"value":"2632-7899","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,1,1]]},"published":{"date-parts":[[2021,1,1]]},"article-number":"sgab014"}}