SynthesisThe international journal of neuropsychopharmacology2026
Efficacy and safety of the muscarinic receptor agonist KarXT (Xanomeline-Trospium) in schizophrenia: a systematic review, meta-analysis and Bayesian sensitivity analysis.
Synthesis in The international journal of neuropsychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed.
- Neurotransmitter Systems in Alzheimer's Disease.Current issues in molecular biology · 2026Review
- Beyond dopamine: KarXT and emerging mechanism-based therapies in schizophrenia.Frontiers in psychiatry · 2026Review
- Emerging non-DFrontiers in psychiatry · 2026Review
- Beyond dopamine blockade: mechanistic humility and the rise of muscarinic, TAAR1, and glutamatergic pathways in schizophrenia.Frontiers in psychiatry · 2026Article
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Authors and funding
15 authors.
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Abstract
backgroundSchizophrenia significantly impacts global health, with existing treatments primarily focusing on positive symptoms and often causing considerable side effects. KarXT (Xanomeline-Trospium), 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.
methodsWe 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.
resultsThree 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 [risk ratio (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.
conclusionKarXT 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.
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Registered trials
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