{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T03:38:13Z","timestamp":1783913893669,"version":"3.55.0"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K08082"],"award-info":[{"award-number":["19K08082"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropsychopharm Rep"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Whether histamine H3 receptor antagonists (H3R\u2010ANTs)\/inverse agonists (H3R\u2010IAs) provides benefit for the treatment of schizophrenia remains unclear. This meta\u2010analysis was conducted to address the above clinical question.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cognitive Function Scale's composite score (primary), seven domains of cognitive function (speed of processing, attention\/vigilance, working memory, verbal learning, visual learning, reasoning\/problem solving, and social cognition) score, University of California San Diego Performance\u2010Based Skills Assessment score, psychopathology scales score, discontinuation rate, and incidence of individual adverse events were among the study outcomes. The standardized mean differences (SMD) or risk ratios (RR) with 95% confidence intervals (CIs) were calculated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our meta\u2010analysis included 11 double\u2010blind, randomized, placebo\u2010controlled trials (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009754). Our study evaluated ABT\u2010288, betahistine, betahistine+reboxetine, GSK239512, MK\u20100249, and pitolisant. Betahistine has an H1\u2010receptor agonistic reaction and H3\u2010receptor antagonistic reaction, while other drugs only have an H3\u2010receptor antagonistic\/inverse agonistic reaction. Hence, we conducted a meta\u2010analysis for all outcomes divided by betahistine or other pooled H3R\u2010ANTs\/H3R\u2010IAs. The study results show that betahistine outperformed placebo in the improvement of overall cognitive symptoms (SMD [95% CI]\u2009=\u2009\u22120.61 [\u22121.03, \u22120.18]), speed of processing (\u22120.44 [\u22120.87, \u22120.02]), attention\/vigilance (\u22120.43 [\u22120.85, \u22120.01]), working memory (\u22120.48 [\u22120.90, \u22120.06]), verbal learning (\u22120.62 [\u22121.04, \u22120.19]), visual learning (\u22120.57 [\u22121.00, \u22120.15]), and betahistine+reboxetine was superior in the improvement of depressive symptoms (\u22124.04 [\u22125.10, \u22122.97]). Pitolisant outperformed placebo in depressive symptom improvement (\u22123.24 [\u22124.22, \u22122.26]). However, the results were derived from one betahistine, betahistine+reboxetine, or pitolisant study. Other pooled H3R\u2010ANTs\/H3R\u2010IAs revealed risk of insomnia (RR [95% CI]\u2009=\u20092.18 [1.05, 4.55]). However, no differences were observed in other any outcomes between betahistine or other pooled H3R\u2010ANTs\/H3R\u2010IAs and placebo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Some H3R\u2010ANTs\/H3R\u2010IAs might provide benefit for the treatment of cognitive symptoms and depressive symptoms in individuals afflicted with schizophrenia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/npr2.70034","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T04:29:34Z","timestamp":1750912174000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Efficacy and Safety of Histamine\n                    <scp>H3<\/scp>\n                    Receptor Antagonist\/Inverse Agonist Including Betahistine for Schizophrenia: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","volume":"45","author":[{"given":"Yasufumi","family":"Nishii","sequence":"first","affiliation":[{"name":"Department of Psychiatry Fujita Health University School of Medicine  Toyoake Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8830-0179","authenticated-orcid":false,"given":"Kenji","family":"Sakuma","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Fujita Health University School of Medicine  Toyoake Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Hamanaka","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Fujita Health University School of Medicine  Toyoake Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nakao","family":"Iwata","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Fujita Health University School of Medicine  Toyoake Aichi 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