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RCT: Xanomeline-trospium reduces psychosis symptoms in patients with schizophrenia – JAMA Psychiatry

2 May, 2024 | 23:24h | UTC

Study Design and Population:

This study, titled EMERGENT-3 (NCT04738123), is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial conducted to evaluate the efficacy and safety of xanomeline-trospium chloride in adults with schizophrenia experiencing acute psychosis. It involved 256 participants across 30 inpatient sites in the US and Ukraine, with the study period running from April 1, 2021, to December 7, 2022. Data analysis occurred from February to June 2023.

 

Main Findings:

The primary outcome was the change from baseline to week 5 in the Positive and Negative Syndrome Scale (PANSS) total score. Xanomeline-trospium significantly reduced the PANSS total score compared to placebo, with a least squares mean difference of -8.4 and a Cohen’s d effect size of 0.60. The most common adverse events were gastrointestinal, mild to moderate in intensity, and generally transient. Safety and tolerability profiles were favorable, with similar discontinuation rates due to adverse events between the xanomeline-trospium and placebo groups.

 

Implications for Practice:

The results of EMERGENT-3, alongside the consistent findings from earlier phases of the trial, affirm xanomeline-trospium’s potential as a novel class of antipsychotic medication. Its mechanism of action, which does not involve D2 dopamine receptor blocking, offers a promising alternative to traditional antipsychotics, particularly for patients who may benefit from different therapeutic approaches due to issues with current treatments.

 

Commentary on X:

 

Reference (link to free full-text):

Kaul, I. et al. (2024). Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. Published online May 1, 2024. doi:10.1001/jamapsychiatry.2024.0785

 


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