Xanomeline-Trospium Chloride as a New Paradigm in the Treatment of Schizophrenia Through Muscarinic Modulation: A Renewed Hope in Psychiatric Care

Schizophrenia remains one of the most challenging clinical issues, despite the efforts made and the number of treatments available to date. This review examines xanomeline-trospium chloride, a novel therapeutic approach to treating schizophrenia by targeting muscarinic acetylcholine receptors (mAChRs). The drug consists of xanomeline, a selective M1/M4 receptor agonist, and trospium, a peripheral muscarinic antagonist, which are used, respectively, to meet central therapeutic needs and avoid peripheral side effects. Xanomeline-trospium chloride has demonstrated clinical efficacy. Moreover, xanomeline-trospium chloride exhibited a better safety profile compared to prior agents, with no major metabolic impact and low discontinuation rates. However, studies show transient mild to moderate gastrointestinal effects. Nevertheless, the clinical trials of this drug have shown that it is effective and well tolerated. Although xanomeline-trospium chloride is already approved for the treatment of schizophrenia, particularly for patients who need better metabolic and cognitive outcomes, future studies should aim to investigate its efficacy in treatment-resistant schizophrenia, early-stage intervention, and other neuropsychiatric disorders. This review aims to integrate the current evidence and assess the potential of xanomeline-trospium chloride as a novel therapeutic approach in the management of schizophrenia.