Evaluating the Role and Efficacy of Cobenfy (Xanomeline and Trospium Chloride) in Schizophrenia Treatment - review
DOI:
https://doi.org/10.12775/QS.2025.40.59815Keywords
Cobenfy, xanomeline-trospium, muscarinic receptor modulation, schizophrenia treatment, non-dopaminergic antipsychotics, EMERGENT trials, antipsychotic therapy.Abstract
Schizophrenia is a complex psychiatric disorder often resistant to dopamine-targeting antipsychotics. Cobenfy, a combination of xanomeline and trospium chloride, offers a novel approach by modulating muscarinic receptors while minimizing side effects. This review evaluates its efficacy and safety, particularly in treatment-resistant cases. Clinical trials show significant reductions in both positive and negative symptoms, positioning Cobenfy as a promising alternative.
References
André Aleman. Neurocognitive Basis of Schizophrenia: Information Processing Abnormalities and Clues for Treatment. Advances in Neuroscience. 2014;2014(1):1-15. https://doi.org/10.1155/2014/104920
Flaum, M., & Schultz, S. K. The Core Symptoms of Schizophrenia. Annals of Medicine. 1996;28(6):525–531. https://doi.org/10.3109/07853899608999116
Tandon R, Gaebel W, Barch DM, et al. Definition and description of schizophrenia in the DSM-5. Schizophrenia research. 2013;150(1):3-10. https://doi.org/10.1016/j.schres.2013.05.028
Williams, J., & First, M. Diagnostic and Statistical Manual of Mental Disorders. Encyclopedia of Social Work. 29 May 2020. https://doi.org/10.1093/acrefore/9780199975839.013.104
Gaebel W, Kerst A, Stricker J. Classification and diagnosis of schizophrenia or other primary psychotic disorders: changes from ICD-10 to ICD-11 and implementation in clinical practice. Psychiatr Danub. 2020;32(3-4):320-324. https://doi.org/10.24869/psyd.2020.320
Valle R. Schizophrenia in ICD-11: Comparison of ICD-10 and DSM-5. Revista de Psiquiatría y Salud Mental (English Edition). 2020;13(2):95-104. https://doi.org/10.1016/j.rpsmen.2020.01.002
First MB, Gaebel W, Maj M, et al. An organization- and category-level comparison of diagnostic requirements for mental disorders in ICD-11 and DSM-5. World Psychiatry. 2021;20(1):34-51. https://doi.org/10.1002/wps.20825
McCutcheon R A., Krystal JH, Howes OD. Dopamine and glutamate in schizophrenia: biology, symptoms and treatment. World Psychiatry. 2020;19(1):15-33. doi:https://doi.org/10.1002/wps.20693
Grace AA. Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression. Nature Reviews Neuroscience. 2016;17(8):524-532. doi:https://doi.org/10.1038/nrn.2016.57
Kaul I, Sawchak S, Walling DP, et al. Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia. JAMA Psychiatry. 2024;81(8). doi:https://doi.org/10.1001/jamapsychiatry.2024.0785
Scarr E, Dean B. Muscarinic receptors: do they have a role in the pathology and treatment of schizophrenia? Journal of Neurochemistry. 2008;107(5):1188-1195. doi:https://doi.org/10.1111/j.1471-4159.2008.05711.x
Velligan DI, Rao S. The Epidemiology and Global Burden of Schizophrenia. The Journal of Clinical Psychiatry. 2023;84(1). https://doi.org/10.4088/jcp.ms21078com5
Charlson FJ, Ferrari AJ, Santomauro DF, et al. Global Epidemiology and Burden of Schizophrenia: Findings From the Global Burden of Disease Study 2016. Schizophrenia Bulletin. 2018;44(6):1195-1203. doi:https://doi.org/10.1093/schbul/sby058
Stilo, S. A., & Murray, R. M. The epidemiology of schizophrenia: replacing dogma with knowledge. Schizophrenia. 2010;12(3):305-315. doi:https://doi.org/10.31887/dcns.2010.12.3/sstilo
Chen J, Cao H, Meyer-Lindenberg A, Schwarz E. Male increase in brain gene expression variability is linked to genetic risk for schizophrenia. Translational Psychiatry. 2018;8(1). doi:https://doi.org/10.1038/s41398-018-0200-0
Janoutová J, Janácková P, Serý O, et al. Epidemiology and risk factors of schizophrenia. Neuro Endocrinology Letters. 2016;37(1):1-8. Available at: https://www.nel.edu/userfiles/articlesnew/NEL370116R01.pdf
Kay SR, Fiszbein A, Opler LA. The Positive and Negative Syndrome Scale (PANSS) for Schizophrenia. Schizophrenia Bulletin. 1987;13(2):261-276. doi:https://doi.org/10.1093/schbul/13.2.261
Kay SR, Opler LA, Lindenmayer JP. The Positive and Negative Syndrome Scale (PANSS): Rationale and Standardisation. British Journal of Psychiatry. 1989;155(S7):59-65. doi:https://doi.org/10.1192/s0007125000291514
NHS. Treatment - Schizophrenia. NHS. Published April 13, 2023. Available at: https://www.nhs.uk/mental-health/conditions/schizophrenia/treatment/
Shapiro DA, Renock S, Arrington E, et al. Aripiprazole, A Novel Atypical Antipsychotic Drug with a Unique and Robust Pharmacology. Neuropsychopharmacology. 2003;28(8):1400-1411. doi:https://doi.org/10.1038/sj.npp.1300203
Nucifora FC, Woznica E, Lee BJ, Cascella N, Sawa A. Treatment resistant schizophrenia: Clinical, biological, and therapeutic perspectives. Neurobiology of Disease. 2019;131:104-257. doi:https://doi.org/10.1016/j.nbd.2018.08.016
Oates JA, Wood AJJ, Baldessarini RJ, Frankenburg FR. Clozapine. New England Journal of Medicine. 1991;324(11):746-754. doi:https://doi.org/10.1056/nejm199103143241107
Sharif Z. Medication adherence in schizophrenia: patient perspectives and the clinical utility of paliperidone ER. Patient Preference and Adherence. 2008;2008(2):233-240. doi:https://doi.org/10.2147/ppa.s3346
Kreyenbuhl J, Buchanan RW, Dickerson FB, Dixon LB. The Schizophrenia Patient Outcomes Research Team (PORT): Updated Treatment Recommendations 2009. Schizophrenia Bulletin. 2009;36(1):94-103. doi:https://doi.org/10.1093/schbul/sbp130
Yıldız M. Psychosocial rehabilitation interventions in the treatment of schizophrenia and bipolar disorder. Archives of Neuropsychiatry. 2021;58(1):77-82. doi:https://doi.org/10.29399/npa.27430
Sinclair DJM, Zhao S, Qi F, Nyakyoma K, Kwong JSW, Adams CE. Electroconvulsive therapy for treatment-resistantschizophrenia. Cochrane Database of Systematic Reviews 2019, Issue 3. Art. No.: CD011847. doi:https://doi.org/10.1002/14651858.CD011847.pub2
Bodick NC, Offen WW, Levey AI, et al. Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease. Arch Neurol. 1997;54(4):465-473. doi: https://doi.org/10.1001/archneur.1997.00550160091022
IUPHAR/BPS Guide to Pharmacology. Xanomeline. Published 2024. Accessed March 16, 2025. Available at:https://www.guidetopharmacology.org
Bakker G, Vingerhoets C, Bloemen OJN, et al. The muscarinic M1 receptor modulates associative learning and memory in psychotic disorders. NeuroImage Clinical. 2020;27:102278. doi:https://doi.org/10.1016/j.nicl.2020.102278
Shekhar A, Potter WZ, Lightfoot J, et al. Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. The American journal of psychiatry. 2008;165(8):1033-1039. doi:https://doi.org/10.1176/appi.ajp.2008.06091591
Breier A, Brannan SK, Paul SM, Miller AC. Evidence of trospium’s ability to mitigate cholinergic adverse events related to xanomeline: phase 1 study results. Psychopharmacology. 2023;240(5):1191-1198. doi:https://doi.org/10.1007/s00213-023-06362-2
U.S. Food and Drug Administration. FDA approves drug with new mechanism of action for the treatment of schizophrenia. Published September 26, 2024. Accessed March 16, 2025. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-drug-new-mechanism-action-treatment-schizophrenia?utm_source=chatgpt.com
U.S. Food and Drug Administration. Drug trials snapshot: Cobenfy. Published September 26, 2024. Accessed March 16, 2025. Available at:https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot-cobenfy?utm_source=chatgpt.com
Correll CU, Angelov AS, Miller AC, Weiden PJ, Brannan SK. Safety and tolerability of KarXT (xanomeline–trospium) in a phase 2, randomized, double-blind, placebo-controlled study in patients with schizophrenia. Schizophrenia. 2022;8(1). doi:https://doi.org/10.1038/s41537-022-00320-1
Bristol Myers Squibb Presents New Long-term Data from the EMERGENT Program Evaluating COBENFYTM (xanomeline and trospium chloride) in Adults with Schizophrenia at Psych Congress 2024. Published 2024. Available at:https://news.bms.com/news/corporate-financial/2024/Bristol-Myers-Squibb-Presents-New-Long-term-Data-from-the-EMERGENT-Program-Evaluating-COBENFY-xanomeline-and-trospium-chloride-in-Adults-with-Schizophrenia-at-Psych-Congress-2024/default.aspx
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Copyright (c) 2025 Michał Mazur, Katarzyna Żak , Katarzyna Michalak , Krystian Zukierski , Weronika Jarych, Aleksandra Pliszka , Hubert Jucha , Katarzyna Madyniak , Agnieszka Kluz
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