Xanomeline/trospium improves cognition in acute schizophrenia patients with impairment

The use of xanomeline/trospium chloride brings significant cognitive improvements to acute schizophrenia patients with prespecified impairments compared with placebo, a study has shown.

“This benefit is not attributable to changes in symptoms despite substantial evidence of efficacy for psychosis,” the authors said.

In this study, the authors pooled data from two 5-week inpatient trials of xanomeline/trospium monotherapy in patients with acute schizophrenia. The statistical analysis plan prespecified comparisons of cognitive composite score changes between the study drug and placebo in the full sample (n=357) and the subgroup of cognitively impaired participants (n=71).

Xanomeline/trospium demonstrated no significant effect in the full sample, but it provided a significantly greater benefit for cognition in the impaired subgroup when compared with placebo (n=66; least squares mean difference, 0.31; d=0.54).

The effect size of xanomeline/trospium significantly increased with a more stringent baseline impairment threshold (≤−1.5 SD; d=0.80). Cognitive improvements showed a minimal association with concurrent changes in total, positive, and negative symptoms in both treatment groups.

“Evaluation of xanomeline/trospium’s potential for cognitive enhancement in a well-controlled trial of stable patients with cognitive impairment is warranted,” the authors said.

“Xanomeline and trospium chloride (formerly known as KarXT), a novel M₁/M₄ muscarinic receptor agonist, demonstrated efficacy across phase II and III trials as monotherapy for the treatment of inpatients with acute schizophrenia on the Positive and Negative Syndrome Scale total score primary endpoint,” they noted.