Xanomeline-Trospium for the Treatment of Schizophrenia

The objective of this review is to examine the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of the combination of xanomeline and trospium (XT) for the treatment of schizophrenia. A search was conducted of all publicly available information (including press releases) and specifically within the databases MEDLINE, Embase, and PsycINFO, from their inception to May 1, 2025, noting the keywords "muscarinic," "schizophrenia," "xanomeline," and "emraclidine." A first-in-class medication approved for the treatment of schizophrenia in adults, XT possesses no direct action on dopamine D₂ receptors. It is dosed twice daily without food and has demonstrated efficacy and safety in three 5-week double-blind, placebo-controlled trials and in two 52-week open-label studies. The pooled effect size of 0.61 (0.56 using the meta-analysis method) is greater than that for other agents approved for schizophrenia since 1996, with no risk for movement disorders, weight gain, and hyperprolactinemia. Post hoc analyses from the acute schizophrenia trials also indicate an impact on cognition among individuals with more significant baseline levels of cognitive impairment. Preliminary results of the adjunctive trial for adults with schizophrenia who are partial responders to other antipsychotics were not statistically significant, but ongoing studies are exploring XT for dementia-related psychosis and pediatric indications.