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The following is a summary of “Does KarXT (xanomeline-trospium) represent a novel approach to schizophrenia management? A GRADE-assessed systematic review and meta-analysis of randomized controlled clinical trials,” published in the March 2025 issue of BMC Psychiatry by Mohammed et al. 

Schizophrenia involves positive, negative, and cognitive symptoms. KarXT (xanomeline-trospium) targets muscarinic receptors, avoiding dopamine blockade. 

Researchers conducted a prospective study to assess KarXT’s efficacy and safety through a systematic review and meta-analysis.  

They searched PubMed, Scopus, Web of Science, and Cochrane for RCTs until October 2024, including studies on adult patients with schizophrenia treated with KarXT. Evidence quality was assessed using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE), and bias was evaluated with Cochrane Risk of Bias 2.0. 

The results showed that four studies with 690 participants were included. KarXT significantly reduced positive and negative syndrome scale (PANSS) total scores versus placebo (mean difference (MD): -13.77, 95% CI [-22.33 to -5.20], P = 0.002) with improvements in positive and negative subscales. It increased the likelihood of ≥30% PANSS reduction (RR: 2.15, 95% CI [1.64 to 2.84], P < 0.00001). KarXT had a favorable safety profile, with mild, transient nausea and constipation, and no significant association with weight gain or extrapyramidal symptoms. 

Investigators highlighted KarXT’s potential in schizophrenia treatment due to its distinct mechanism and tolerability. They emphasized the need for future studies on long-term efficacy, delayed adverse effects, and comparative effectiveness. 

Source: bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-025-06696-5