Efficacy and safety of xanomeline-trospium chloride in schizophrenia: A systematic review and meta-analysis.

Abstract

Introduction: Schizophrenia is one of the psychiatric illnesses with a higher mortality rate. Xanomeline, an oral muscarinic receptor agonist, combined with Trospium, a pan-muscarinic receptor antagonist, represents a promising new treatment for schizophrenia that has been tested in clinical trials. Herein, we aimed to perform a meta-analysis assessing Xanomeline-Trospium Chloride's (XTC) safety and efficacy for treating schizophrenia.

Materials and methods: MEDLINE, EMBASE, and Cochrane databases were searched for randomized clinical trials testing XTC safety and efficacy in patients with schizophrenia on May 03, 2024. The research protocol was registered with the International Prospective Register of Systematic Reviews (CRD42024547487). Data were examined using the Mantel-Haenszel method and 95% CIs. Heterogeneity was assessed using I² statistics. R, version 4.3.2, was used for statistical analysis.

Results: 3 RCTs and 674 patients were included, of whom 332 (49%) received XTC. The change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score was significantly higher in the XTC arm (MD -13.17; 95% CI -20.16 to -6.18; P = 0.0002; I² = 100%). Treatment with XTC resulted in improvements across all subscales of the PANSS. Additionally, XTC was associated with the occurrence of cholinergic adverse events, including nausea (18,52% vs. 3,79%; RR 4.37; 95% CI 2.43 to 7.84; P < 0.000001; I² = 19%) but was not associated with akathisia (MD -0.00; 95% CI -0.13 to 0.13; P = 0.9; I² = 0%) or body weight gain (MD -0.36; 95% CI -1.18 to 0.46; P = 0.38; I² = 51%).

Conclusion: XTC is effective in improving schizophrenia symptoms. However, it is associated with some bothersome AEs that may undermine its tolerability and lead to increased discontinuation rates, despite its efficacy.