{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:33:24Z","timestamp":1790202804940,"version":"4.1.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T00:00:00Z","timestamp":1743724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014387","name":"Acadia Pharmaceuticals Inc","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014387","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Hypotheses<\/jats:title>\n                    <jats:p>Negative symptoms of schizophrenia (NSS) carry a substantial burden, and there are no treatments currently approved for NSS. The efficacy of pimavanserin, a selective 5-HT2A inverse agonist and antagonist, in treating NSS was assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design<\/jats:title>\n                    <jats:p>ADVANCE-2 was a phase 3, randomized, double-blind, placebo-controlled study of pimavanserin in patients with schizophrenia and predominantly negative symptoms. Patients were randomized (1:1) to receive pimavanserin (34 mg\/day) or placebo alongside ongoing background antipsychotic medication. Eligible adults were aged 18\u201355 years and had access to a caregiver. The primary and key secondary endpoints were the change from baseline to week 26 in the Negative Symptom Assessment\u201316 (NSA-16) total score and Clinical Global Impression\u2013Schizophrenia Scale-Severity (CGI-SCH-S) negative symptom score, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Results<\/jats:title>\n                    <jats:p>Of the 454 randomized patients, 71 (39 placebo; 32 pimavanserin) discontinued and 383 (188 placebo; 195 pimavanserin) completed the study. The safety and full analysis sets comprised 453 and 446 patients, respectively. The NSA-16 change from baseline to week 26 was not significantly different between groups (least squares mean difference: \u22120.67; SE, 0.95; [95% CI: \u22122.54, 1.20]; P\u2005=\u2005.48; Cohen\u2019s d effect size: 0.07). Treatment-emergent adverse events occurred in 30.4% with pimavanserin and 40.3% with placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this study, pimavanserin was well tolerated, and although it demonstrated a similar treatment effect as in the prior phase 2 study favoring pimavanserin, treatment with pimavanserin vs placebo did not result in significant differences for primary or other endpoints.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/schbul\/sbaf034","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T07:48:58Z","timestamp":1740469738000},"source":"Crossref","is-referenced-by-count":5,"title":["A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Pimavanserin as an Adjunctive Treatment for the Negative Symptoms of Schizophrenia (ADVANCE-2) in Patients With Predominant Negative Symptoms"],"prefix":"10.1093","volume":"52","author":[{"given":"Dragana","family":"Bugarski-Kirola","sequence":"first","affiliation":[{"name":"Clinical Research,\u00a0Acadia Pharmaceuticals GmbH , Basel ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Acadia Pharmaceuticals Inc. , San Diego, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso","family":"Arango","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, IiSGM, School of Medicine, Universidad Complutense , Madrid ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0288-309X","authenticated-orcid":false,"given":"Stephen R","family":"Marder","sequence":"additional","affiliation":[{"name":"Semel Institute for Neuroscience, University of California Los Angeles , Los Angeles, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,4,4]]},"reference":[{"key":"2026011701163226200_CIT0001","doi-asserted-by":"crossref","first-page":"519","DOI":"10.2147\/NDT.S225643","article-title":"Negative symptoms in schizophrenia: a review and clinical guide for recognition, assessment, and treatment","volume":"16","author":"Correll","year":"2020","journal-title":"Neuropsychiatr Dis Treat."},{"key":"2026011701163226200_CIT0002","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/S2215-0366(18)30050-6","article-title":"Negative symptoms of schizophrenia: new 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