{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T07:17:05Z","timestamp":1788592625457,"version":"build-2803163510"},"reference-count":22,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Child and Adolescent Psychopharmacology"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction:<\/jats:title>\n                    <jats:p>The effective management of irritability is a key need in young people with autism spectrum disorder (ASD). We evaluated the efficacy and safety of brexpiprazole in children and adolescents with irritability associated with ASD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>This was an 8-week, phase 3, randomized, double-blind, placebo-controlled trial (NCT04174365) and 26-week, open-label extension (OLE, NCT04258839) of brexpiprazole (0.25\u20133 mg\/day based on body weight) in children and adolescents (5\u201317 years) with a diagnosis of ASD, score \u226518 on the Aberrant Behavior Checklist\u2013Irritability (ABC-I) subscale, and score \u22654 on the Clinical Global Impressions\u2013Severity scale.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Of the 119 randomized participants (brexpiprazole = 60, placebo = 59), 104 completed double-blind treatment, and 95 enrolled and 70 completed the OLE. Similar reductions in mean ABC-I subscale score were seen in both groups (least-squares mean \u00b1 standard error reduction from double-blind baseline of \u221210.1\u2009\u00b1\u20091.3 with brexpiprazole vs \u22128.9\u2009\u00b1\u20091.3 with placebo). Thus, the primary endpoint did not show a significant treatment effect (LS-mean [95% confidence interval] treatment difference: \u20131.22 [\u20134.49, 2.05],\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.46) and the hierarchical efficacy analysis ended at this point. At the end of the OLE, participants had a mean \u00b1 SD reduction from open-label baseline of \u22126.1\u2009\u00b1\u20098.2 in ABC-I subscale score. During double-blind treatment, 51.7% participants treated with brexpiprazole had \u22651 treatment-emergent adverse event (TEAE) versus 35.1% with placebo; no severe or serious TEAEs were reported. The only potentially treatment-related TEAE that occurred in \u22655% of participants was somnolence (12.1% for brexpiprazole vs 5.3% for placebo). During the OLE, the most commonly reported TEAE was increased weight (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 13, 13.7%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Treatment with brexpiprazole did not demonstrate significant efficacy versus placebo for the treatment of irritability associated with ASD. The safety profile was consistent with that observed in adult and adolescent patients with schizophrenia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/cap.2024.0118","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T12:19:01Z","timestamp":1739967541000},"page":"194-201","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Safety and Efficacy of Brexpiprazole in the Treatment of Irritability Associated with Autism Spectrum Disorder: An 8-Week, Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial and 26-Week Open-Label Extension in Children and Adolescents"],"prefix":"10.1177","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4857-7397","authenticated-orcid":false,"given":"Caroline","family":"Ward","sequence":"first","affiliation":[{"name":"Otsuka Pharmaceutical Development &amp; Commercialization, Inc., Rockville, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5782-7891","authenticated-orcid":false,"given":"Ann","family":"Childress","sequence":"additional","affiliation":[{"name":"Center for Psychiatry and Behavioral Medicine, Inc, Las Vegas, Nevada, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista","family":"Martinko","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development &amp; Commercialization, Inc., Rockville, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalei","family":"Chen","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development &amp; Commercialization, Inc., Rockville, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus Groes","family":"Larsen","sequence":"additional","affiliation":[{"name":"H. Lundbeck A\/S, Valby, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alpesh","family":"Shah","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development &amp; Commercialization, Inc., Rockville, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Sheridan","sequence":"additional","affiliation":[{"name":"Lundbeck US, Deerfield, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanco","family":"Hefting","sequence":"additional","affiliation":[{"name":"H. Lundbeck A\/S, Valby, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Knutson","sequence":"additional","affiliation":[{"name":"Core Clinical Research, Everett, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"e_1_3_5_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/frcha.2024.1393231"},{"issue":"5","key":"e_1_3_5_3_1","first-page":"485","article-title":"The aberrant behavior checklist: A behavior rating scale for the assessment of treatment effects","volume":"89","author":"Aman MG","year":"1985","unstructured":"Aman MG, , Singh NN, , Stewart AW, et al. The aberrant behavior checklist: A behavior rating scale for the assessment of treatment effects. 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