{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:34:40Z","timestamp":1792629280342,"version":"4.5.0"},"reference-count":31,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"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":["Ann Pharmacother"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>This review describes a novel combination muscarinic agonist and antagonist, xanomeline-trospium, which was recently approved by the Food and Drug Administration (FDA) for schizophrenia. Efficacy and safety evidence from phase II and III clinical trials are reviewed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Sources:<\/jats:title>\n                    <jats:p>The MEDLINE and EMBASE databases were searched in 2024; terms included \u201cxanomeline trospium\u201d OR \u201cxanomelinetrospium\u201d OR \u201cKarXT\u201d OR \u201cCobenfy\u201d AND \u201cschizophrenia.\u201d The search was repeated in January 2025. Clinicaltrials.gov was used to review ongoing or unpublished studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Selection and Data Extraction:<\/jats:title>\n                    <jats:p>Human subject studies of xanomeline-trospium were included.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Synthesis:<\/jats:title>\n                    <jats:p>\n                      In phase III trials, xanomeline-trospium was superior to placebo for acute exacerbation of schizophrenia. EMERGENT-2 and EMERGENT-3 found patients improved by 9.6 and 8.4 points on the Positive and Negative Symptom Scale (PANSS), respectively, compared with placebo (95% confidence interval \u201313.9 to \u20135.2,\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001 and \u201312.4 to \u20134.3,\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001). Participants in EMERGENT-4, a long-term open-label extension study, who received the intervention in the randomized phases experienced a 9-point decrease in PANSS from the last result.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:<\/jats:title>\n                    <jats:p>Xanomeline-trospium is a novel antipsychotic that is effective for treatment of schizophrenia and may have a favorable adverse effect profile in comparison with other antipsychotics due to its lack of dopamine receptor antagonism. Efficacy for improvement in negative symptoms and cognitive function in schizophrenia is promising.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Xanomeline-trospium shows promising results for treatment of schizophrenia. Further studies with active comparators, larger sample sizes, and more patients with prominent negative symptoms are needed to corroborate efficacy and determine place in therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10600280251324642","type":"journal-article","created":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T06:55:02Z","timestamp":1743058502000},"page":"937-950","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Xanomeline-Trospium: A Novel Therapeutic for the Treatment of Schizophrenia"],"prefix":"10.1177","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6149-1366","authenticated-orcid":false,"given":"Olivia L.","family":"Ramey","sequence":"first","affiliation":[{"name":"Division of Pharmacotherapy and Translational Sciences, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA"},{"name":"University Health, San Antonio, TX, USA"},{"name":"Long School of Medicine, Pharmacotherapy Education and Research Center, University of Texas Health Science Center, San Antonio, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9601-9413","authenticated-orcid":false,"given":"Armando","family":"Silva Almod\u00f3var","sequence":"additional","affiliation":[{"name":"PharmPix Corp., Guaynabo, Puerto Rico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"e_1_3_3_2_2","unstructured":"National Institute of Mental Health. Schizophrenia. Accessed November 19 2024. https:\/\/www.nimh.nih.gov\/health\/statistics\/schizophrenia#part_2543"},{"key":"e_1_3_3_3_2","unstructured":"National Institute of Mental Health (NIMH). Suicide. Published February 2024. Accessed January 15 2025. https:\/\/www.nimh.nih.gov\/health\/statistics\/suicide"},{"key":"e_1_3_3_4_2","unstructured":"NHS. Symptoms\u2014Schizophrenia. Published April 13 2023. Accessed November 19 2024. https:\/\/www.nhs.uk\/mental-health\/conditions\/schizophrenia\/symptoms\/"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2020.177901"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.2147\/nedt.2006.2.4.531"},{"key":"e_1_3_3_7_2","volume-title":"Cobenfy (Xanomeline-Trospium). Package Insert","author":"Bristol-Myers Squibb Company","year":"2024","unstructured":"Bristol-Myers Squibb Company. Cobenfy (Xanomeline-Trospium). Package Insert. Bristol-Myers Squibb Company; 2024."},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-023-06362-2"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2017015"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)02190-6"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2024.0785"},{"key":"e_1_3_3_12_2","unstructured":"Bristol-Myers Squibb. An extension study to assess long-term safety tolerability and efficacy of KarXT in adult patients with Schizophrenia (EMERGENT-4). Clinicaltrials.gov identifier: NCT04659174. Updated October 28 2024. Accessed January 20 2025. https:\/\/clinicaltrials.gov\/study\/NCT04659174?intr=Xanomeline%20and%20Trospium%20Chloride%20Capsules&rank=1"},{"key":"e_1_3_3_13_2","unstructured":"Bristol-Myers Squibb. An open-label study to assess the long-term safety tolerability and efficacy of KarXT in adult patients with Schizophrenia (EMERGENT-5). Clinicaltrials.gov identifier: NCT04820309. Updated August 20 2024. Accessed January 20 2025. https:\/\/clinicaltrials.gov\/study\/NCT04820309?intr=Xanomeline%20and%20Trospium%20Chloride%20Capsules&rank=2#study-overview"},{"issue":"10","key":"e_1_3_3_14_2","first-page":"43","article-title":"Xanomeline and trospium: a potential fixed drug combination (FDC) for schizophrenia-a brief review of current data","volume":"19","author":"Singh A.","year":"2022","unstructured":"Singh A. Xanomeline and trospium: a potential fixed drug combination (FDC) for schizophrenia-a brief review of current data. Innov Clin Neurosci. 2022;19(10-12):43-47.","journal-title":"Innov Clin Neurosci"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST20220525"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.21101083"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.11m07162"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.21m14316"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-02254-9"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41537-022-00320-1"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/arclin\/acp010"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(19)30416-X"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2024.08.001"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S225643"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41537-024-00525-6"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.5498\/wjp.v2.i5.74"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-016-4450-3"},{"key":"e_1_3_3_28_2","unstructured":"Bristol-Myers Squibb. 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