Efficacy and Safety of the Muscarinic Receptor Agonist KarXT (Xanomeline-Trospium) in Schizophrenia: A Systematic Review, Meta-Analysis and Bayesian Sensitivity Analysis.
Nikhil Sharma, Mahalaqua Nazli Khatib, R Roopashree, Mandeep Kaur, Manish Srivastava, Amit Barwal, G V Siva Prasad, Pranchal Rajput, Vinamra Mittal, Muhammed Shabil, Amit Kumar, Ganesh Bushi, Rachana Mehta, Prakasini Satapathy, Sanjit Sah
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引用次数: 0
Abstract
Background: Schizophrenia significantly impacts global health, with existing treatments primarily focusing on positive symptoms and often causing considerable side effects. KarXT, a novel treatment combining xanomeline, a muscarinic M1/M4 receptor agonist, and trospium, targets a broader range of symptoms including negative and cognitive deficits, potentially with fewer side effects. This systematic review and meta-analysis evaluates the efficacy and safety of KarXT in treating schizophrenia, assessing symptom reduction and safety profiles compared to placebo.
Methods: We searched PubMed, Embase, and Web of Science up to November 10, 2024, for randomized controlled trials (RCTs) assessing the efficacy and safety of KarXT in schizophrenia. Data were pooled using a random-effects model, assessing outcomes like Positive and Negative Syndrome Scale (PANSS) scores and incidence of treatment-emergent adverse events (TEAEs). R software (Version 4.4.) was used for meta-analysis.
Results: Three RCTs involving 674 participants were included. KarXT significantly reduced total PANSS scores of mean difference (MD) -9.707 (95% CI: -12.329 to -7.085), with notable improvements in both negative (MD = -1.623; 95% CI: -2.461 to -0.785) and positive symptom subscales (MD = -3.213; 95% CI: -4.033 to -2.393). The treatment was associated with a higher incidence of TEAEs, predominantly constipation (RR: 2.77; 95% CI: 1.72-4.45) and nausea (RR: 4.87; 95% CI: 2.73-8.68) compared to placebo. Bayesian meta-analysis confirmed the results.
Conclusion: KarXT offers significant improvements in both negative and positive symptoms of schizophrenia with a manageable safety profile. Its potential as a transformative treatment for schizophrenia highlights the need for further research to confirm these findings and to fully understand its long-term efficacy and safety.
期刊介绍：
The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.
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