{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:17:42Z","timestamp":1781108262465,"version":"3.54.1"},"reference-count":30,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100004686","name":"Deanship of Scientific Research, King Faisal University","doi-asserted-by":"publisher","award":["KFU252127"],"award-info":[{"award-number":["KFU252127"]}],"id":[{"id":"10.13039\/501100004686","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Agitation in Alzheimer's disease significantly impacts patient outcomes and caregiver burden. Brexpiprazole has emerged as a promising treatment option, but optimal dosing remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the comparative efficacy and safety of different brexpiprazole doses in treating agitation associated with Alzheimer's disease through a systematic review and network meta-analysis (NMA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Following PRISMA guidelines, we searched PubMed, Embase, Web of Science, and Scopus through January 2025. Four randomized controlled trials (N\u2009=\u20091451) comparing various brexpiprazole doses (0.5\u20133\u2005mg\/day) with placebo were included. Primary outcomes included changes in the Cohen-Mansfield Agitation Inventory (CMAI), the Clinical Global Impression-Severity Scale (CGI-S), and the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH) scores, alongside safety measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Brexpiprazole 2\u2005mg demonstrated significant improvement in CMAI scores versus placebo (mean difference [MD]: \u22125.88; 95% CI: \u22128.13 to \u22123.63) and CGI-S scores (MD: \u22120.48; 95% CI: \u22120.95 to \u22120.01). Multiple doses showed significant NPI-NH improvements, with 2\u20133\u2005mg showing the strongest effect (MD: \u22124.60; 95% CI: \u22127.54 to \u22121.66). Higher doses (2\u20133\u2005mg) increased treatment-emergent adverse events (risk ratio [RR]: 1.20\u20131.33) but showed no significant difference in serious adverse events compared to placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Brexpiprazole 2\u2005mg provides optimal therapeutic benefit while maintaining a favorable safety profile. The findings support initiating treatment at lower doses with careful titration to 2\u2005mg based on individual response and tolerability. Future research should focus on long-term outcomes and real-world effectiveness.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251404500","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T13:11:29Z","timestamp":1765199489000},"page":"1089-1098","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparative efficacy and safety of different brexpiprazole doses for agitation in Alzheimer's disease: A systematic review and network meta-analysis"],"prefix":"10.1177","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3668-5147","authenticated-orcid":false,"given":"Mahmoud","family":"Kandeel","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Delta University for Science and Technology, Gamasa, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12694"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2012.00073"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1017\/S104161022200103X"},{"key":"e_1_3_3_5_2","article-title":"Behavioral and psychological symptoms of dementia and their management","volume":"51","author":"Kar N","year":"2009","unstructured":"Kar N. Behavioral and psychological symptoms of dementia and their management. Indian J Psychiatry 2009; 51: S77\u2013S86.","journal-title":"Indian J Psychiatry"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/gps.5244"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jagp.2019.05.012"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1092852924000427"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410200510"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410190307"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-161118"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.05.2410"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.2147\/CIA.S399697"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.644317"},{"key":"e_1_3_3_15_2","article-title":"Antipsychotics for agitation and psychosis in people with Alzheimer's disease and vascular dementia","volume":"12","author":"M\u00fchlbauer V","year":"2021","unstructured":"M\u00fchlbauer V, M\u00f6hler R, Dichter MN, et al. Antipsychotics for agitation and psychosis in people with Alzheimer's disease and vascular dementia. Cochrane Database Syst Rev 2021; 12: CD013304.","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1103039"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1177\/2040622312452387"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2024.105173"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.3371\/CSRP.MCCI.010316"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.3810"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14282"},{"key":"e_1_3_3_22_2","article-title":"Updated guidance for trusted systematic reviews: a new edition of the cochrane handbook for systematic reviews of interventions","volume":"10","author":"Cumpston M","year":"2019","unstructured":"Cumpston M, Li T, Page MJ, et al. Updated guidance for trusted systematic reviews: a new edition of the cochrane handbook for systematic reviews of interventions. Cochrane Database Syst Rev 2019; 10: ED000142.","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2009.06.006"},{"key":"e_1_3_3_24_2","article-title":"Rob 2: a revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne JAC","year":"2019","unstructured":"Sterne JAC, Savovi\u0107 J, Page MJ, et al. Rob 2: a revised tool for assessing risk of bias in randomised trials. Br Med J 2019; 366: l4898.","journal-title":"Br Med J"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jagp.2019.09.009"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2024.1379062"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1177\/15333175221082834"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2015.01.014"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X15666170413115754"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-024-07576-8"},{"key":"e_1_3_3_31_2","unstructured":"FDA Approves First Drug to Treat Agitation Symptoms Associated with Dementia Due to Alzheimer\u2019s Disease. https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-first-drug-treat-agitation-symptoms-associated-dementia-due-alzheimers-disease. 2023."}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877251404500","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13872877251404500","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877251404500","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:09:48Z","timestamp":1777370988000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13872877251404500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,8]]},"references-count":30,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1177\/13872877251404500"],"URL":"https:\/\/doi.org\/10.1177\/13872877251404500","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,8]]}}}