Is muscarinic receptor agonist effective and tolerant for schizophrenia?

Abstract Background Several randomized clinical trials (RCTs) have recently examined the efficacy and tolerability of muscarinic receptor agonists in schizophrenia. However, whether therapeutics targeting muscarinic receptors improve symptom management and reduce side effects remains systemically un...

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Main Authors: Xiaonan Guo, Rongshan Deng, Jianbo Lai, Shaohua Hu
Format: Article
Language:English
Published: BMC 2025-04-01
Series:BMC Psychiatry
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Online Access:https://doi.org/10.1186/s12888-025-06662-1
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author Xiaonan Guo
Rongshan Deng
Jianbo Lai
Shaohua Hu
author_facet Xiaonan Guo
Rongshan Deng
Jianbo Lai
Shaohua Hu
author_sort Xiaonan Guo
collection DOAJ
description Abstract Background Several randomized clinical trials (RCTs) have recently examined the efficacy and tolerability of muscarinic receptor agonists in schizophrenia. However, whether therapeutics targeting muscarinic receptors improve symptom management and reduce side effects remains systemically unexplored. Methods Embase, PubMed, and Web of Science were searched from inception until Jan 9, 2025. Altogether, the efficacy and safety outcomes of four RCTs (397 individuals in the muscarinic receptor agonists group, and 374 in the placebo control group) were meta-analyzed. To compare scores of positive and negative syndrome scale (PANSS), response rate, discontinuation rate, and adverse events with muscarinic receptor agonists vs. placebo in patients with schizophrenia, scale changes were pooled as mean difference (MD) for continuous outcomes and risk ratio (RR) for categorical outcomes. Results It revealed that muscarinic receptor agonists were superior to placebo in terms of decrease in the total PANSS score (MD, − 9.92; 95% CI, -12.46 to -7.37; I2 = 0%), PANSS positive symptom subscore (MD, − 3.21; 95% CI, -4.02 to -2.40; I2 = 0%), and PANSS negative symptom subscore (MD, -1.79; 95% CI, -2.47 to -1.11; I2 = 48%). According to the study-defined response rate, the pooled muscarinic receptor agonists vs. placebo RR was 2.08 (95% CI, 1.59 to 2.72; I2 = 0%). No significance was found in the discontinuation rate. Muscarinic receptor agonists were associated with a higher risk of nausea (RR = 4.61, 95% CI, 2.65 to 8.02; I2 = 3%), and in particular, xanomeline-trospium was associated with risks of dyspepsia, vomiting, and constipation. Conclusions The findings highlighted an efficacy advantage with tolerated adverse event profiles for muscarinic receptor agonists in schizophrenia.
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spelling doaj-art-e7eabd08464141cfa2bd1151058108982025-08-20T03:07:44ZengBMCBMC Psychiatry1471-244X2025-04-0125111010.1186/s12888-025-06662-1Is muscarinic receptor agonist effective and tolerant for schizophrenia?Xiaonan Guo0Rongshan Deng1Jianbo Lai2Shaohua Hu3Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Psychiatry, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Psychiatry, the First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Psychiatry, the First Affiliated Hospital, Zhejiang University School of MedicineAbstract Background Several randomized clinical trials (RCTs) have recently examined the efficacy and tolerability of muscarinic receptor agonists in schizophrenia. However, whether therapeutics targeting muscarinic receptors improve symptom management and reduce side effects remains systemically unexplored. Methods Embase, PubMed, and Web of Science were searched from inception until Jan 9, 2025. Altogether, the efficacy and safety outcomes of four RCTs (397 individuals in the muscarinic receptor agonists group, and 374 in the placebo control group) were meta-analyzed. To compare scores of positive and negative syndrome scale (PANSS), response rate, discontinuation rate, and adverse events with muscarinic receptor agonists vs. placebo in patients with schizophrenia, scale changes were pooled as mean difference (MD) for continuous outcomes and risk ratio (RR) for categorical outcomes. Results It revealed that muscarinic receptor agonists were superior to placebo in terms of decrease in the total PANSS score (MD, − 9.92; 95% CI, -12.46 to -7.37; I2 = 0%), PANSS positive symptom subscore (MD, − 3.21; 95% CI, -4.02 to -2.40; I2 = 0%), and PANSS negative symptom subscore (MD, -1.79; 95% CI, -2.47 to -1.11; I2 = 48%). According to the study-defined response rate, the pooled muscarinic receptor agonists vs. placebo RR was 2.08 (95% CI, 1.59 to 2.72; I2 = 0%). No significance was found in the discontinuation rate. Muscarinic receptor agonists were associated with a higher risk of nausea (RR = 4.61, 95% CI, 2.65 to 8.02; I2 = 3%), and in particular, xanomeline-trospium was associated with risks of dyspepsia, vomiting, and constipation. Conclusions The findings highlighted an efficacy advantage with tolerated adverse event profiles for muscarinic receptor agonists in schizophrenia.https://doi.org/10.1186/s12888-025-06662-1SchizophreniaMuscarinic receptor agonistXanomeline-trospium
spellingShingle Xiaonan Guo
Rongshan Deng
Jianbo Lai
Shaohua Hu
Is muscarinic receptor agonist effective and tolerant for schizophrenia?
BMC Psychiatry
Schizophrenia
Muscarinic receptor agonist
Xanomeline-trospium
title Is muscarinic receptor agonist effective and tolerant for schizophrenia?
title_full Is muscarinic receptor agonist effective and tolerant for schizophrenia?
title_fullStr Is muscarinic receptor agonist effective and tolerant for schizophrenia?
title_full_unstemmed Is muscarinic receptor agonist effective and tolerant for schizophrenia?
title_short Is muscarinic receptor agonist effective and tolerant for schizophrenia?
title_sort is muscarinic receptor agonist effective and tolerant for schizophrenia
topic Schizophrenia
Muscarinic receptor agonist
Xanomeline-trospium
url https://doi.org/10.1186/s12888-025-06662-1
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