{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:55:18Z","timestamp":1792799718454,"version":"4.5.0"},"reference-count":36,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021138","name":"Lundbeck Canada","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100021138","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Otsuka Pharmaceutical Development & Commercialization Inc.","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/001nxvg84","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100013327","name":"H. Lundbeck A\/S","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100013327","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018864","name":"Otsuka Canada Pharmaceutical","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100018864","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Can J Psychiatry"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To characterize the effects of adjunctive brexpiprazole on patient life engagement and depressive symptoms in patients with major depressive disorder (MDD) using patient-reported outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An 8-week, Phase 4, open-label, interventional study was conducted at 15 Canadian trial sites between April 2021 and May 2022. Adult outpatients with MDD (at least moderately severe) and inadequate response to 1\u20132 antidepressants continued their current antidepressant and received oral adjunctive brexpiprazole 0.5\u20132\u2005mg\/day. Co-primary endpoints were change from baseline to Week 8 in Inventory of Depressive Symptomatology Self-Report (IDS-SR) 10-item Life Engagement subscale score, and IDS-SR 30-item total score. Safety was assessed by standard variables.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 122 enrolled patients, 120 (98.4%) were treated (mean [ SD] dose: 1.2 [0.4] mg\/day) and analyzed, and 111 (91.0%) completed the study. Statistically significant least squares mean improvements to Week 8 were observed on IDS-SR\n                      <jats:sub>10<\/jats:sub>\n                      Life Engagement subscale score (baseline mean [ SD]: 16.1 [4.7]; change [95% confidence interval]: \u22128.11 [\u22129.34, \u22126.88]; p\u2009&lt;\u20090.001) and IDS-SR total score (baseline mean [ SD]: 41.3 [9.8]; change [95% confidence interval]: \u221217.38 [\u221220.08, \u221214.68]; p\u2009&lt;\u20090.001). Improvements were observed from Week 2, onwards. Treatment-emergent adverse events with incidence \u22655% were fatigue ( n\u2009=\u200913, 10.8%), headache ( n\u2009=\u200913, 10.8%), insomnia ( n\u2009=\u200912, 10.0%), nausea ( n\u2009=\u20099, 7.5%), tremor ( n\u2009=\u20098, 6.7%), and weight increase ( n\u2009=\u20097, 5.8%). Six patients (5.0%) discontinued due to adverse events. Mean ( SD) change in body weight from baseline to last visit was +1.9 (3.4) kg.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Using an exploratory patient-reported outcome measure, patients with MDD and inadequate response to antidepressants who received open-label adjunctive brexpiprazole showed early and clinically meaningful improvement in patient life engagement, which should be further assessed in a prospective randomized controlled trial. Patient-rated depressive symptoms (on the validated 30-item IDS-SR) also improved. Adjunctive brexpiprazole was well tolerated, and no new safety signals were observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov identifier: NCT04830215.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/07067437241233965","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T03:15:55Z","timestamp":1709262955000},"page":"513-523","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Adjunctive Brexpiprazole for Patient Life Engagement in Major Depressive Disorder: A Canadian, Phase 4, Open-Label, Interventional Study: Brexpiprazole d'appoint pour l'engagement dans la vie des patients souffrant de trouble d\u00e9pressif majeur: une \u00e9tude interventionnelle canadienne ouverte de phase 4"],"prefix":"10.1177","volume":"69","author":[{"given":"Fran\u00e7ois","family":"Therrien","sequence":"first","affiliation":[{"name":"Otsuka Canada Pharmaceutical Inc., Saint-Laurent, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Ward","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratap","family":"Chokka","sequence":"additional","affiliation":[{"name":"Chokka Center for Integrative Health, Edmonton, Alberta, Canada"},{"name":"Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0009-3182","authenticated-orcid":false,"given":"Jeffrey","family":"Habert","sequence":"additional","affiliation":[{"name":"Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5529-3731","authenticated-orcid":false,"given":"Zahinoor","family":"Ismail","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry, Clinical Neurosciences, and Community Health Sciences; Hotchkiss Brain Institute and O\u2019Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada"},{"name":"Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger S.","family":"McIntyre","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin M.","family":"MacKenzie","sequence":"additional","affiliation":[{"name":"Lundbeck Canada Inc., Saint-Laurent, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,3,1]]},"reference":[{"key":"bibr1-07067437241233965","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425787"},{"key":"bibr2-07067437241233965","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.163.1.148"},{"key":"bibr3-07067437241233965","doi-asserted-by":"publisher","DOI":"10.1186\/s41687-021-00380-4"},{"key":"bibr4-07067437241233965","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-018-0381-z"},{"key":"bibr5-07067437241233965","doi-asserted-by":"publisher","DOI":"10.1186\/s41687-022-00517-z"},{"key":"bibr6-07067437241233965","doi-asserted-by":"publisher","DOI":"10.2147\/PROM.S156279"},{"key":"bibr7-07067437241233965","doi-asserted-by":"publisher","DOI":"10.1186\/s41687-022-00468-5"},{"key":"bibr8-07067437241233965","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2023.02.008"},{"key":"bibr9-07067437241233965","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.114.213793"},{"key":"bibr10-07067437241233965","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.14m09688"},{"key":"bibr11-07067437241233965","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.14m09689"},{"key":"bibr12-07067437241233965","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.17m12058"},{"key":"bibr13-07067437241233965","doi-asserted-by":"publisher","DOI":"10.1080\/03007995.2018.1430220"},{"key":"bibr14-07067437241233965","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2023.04.012"},{"key":"bibr15-07067437241233965","doi-asserted-by":"publisher","DOI":"10.2147\/CEOR.S395255"},{"key":"bibr16-07067437241233965","unstructured":"Otsuka Pharmaceutical Co. 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