A randomized clinical trial evaluated the efficacy and safety of xanomeline-trospium chloride (KarXT) in adults with schizophrenia experiencing acute psychosis. The trial, EMERGENT-3, involved 256 participants randomized to receive either xanomeline-trospium (maximum dose 125 mg xanomeline and 30 mg trospium) or placebo for 5 weeks. Xanomeline-trospium significantly reduced the Positive and Negative Syndrome Scale (PANSS) total score compared to placebo, with a mean difference of -8.4 points (95% CI, -12.4 to -4.3; P < .001). The effect size was moderate (Cohen d = 0.60). Xanomeline-trospium was generally well tolerated, with the most common adverse events being gastrointestinal (nausea, dyspepsia, vomiting, constipation), which were mild to moderate and transient. Discontinuation rates due to treatment-emergent adverse events (TEAEs) were similar between groups (6.4% vs 5.5%). No clinically meaningful changes in extrapyramidal symptoms, weight gain, or somnolence were observed between treatment groups. Xanomeline-trospium was associated with a significantly greater reduction in positive symptoms compared to placebo. The findings support the potential of xanomeline-trospium as a new class of antipsychotics with a different mechanism of action, targeting muscarinic receptors and not associated with the adverse effects of dopamine receptor antagonists, such as extrapyramidal symptoms, weight gain, or somnolence. These results are consistent with previous trials (EMERGENT-1 and EMERGENT-2), reinforcing the efficacy and safety of xanomeline-trospium in schizophrenia. The trial was conducted in accordance with ethical and regulatory standards, and data were analyzed using appropriate statistical methods. Limitations include the short duration of the trial and the absence of an active comparator group. Further long-term studies are needed to assess the durability of the treatment effect and safety.A randomized clinical trial evaluated the efficacy and safety of xanomeline-trospium chloride (KarXT) in adults with schizophrenia experiencing acute psychosis. The trial, EMERGENT-3, involved 256 participants randomized to receive either xanomeline-trospium (maximum dose 125 mg xanomeline and 30 mg trospium) or placebo for 5 weeks. Xanomeline-trospium significantly reduced the Positive and Negative Syndrome Scale (PANSS) total score compared to placebo, with a mean difference of -8.4 points (95% CI, -12.4 to -4.3; P < .001). The effect size was moderate (Cohen d = 0.60). Xanomeline-trospium was generally well tolerated, with the most common adverse events being gastrointestinal (nausea, dyspepsia, vomiting, constipation), which were mild to moderate and transient. Discontinuation rates due to treatment-emergent adverse events (TEAEs) were similar between groups (6.4% vs 5.5%). No clinically meaningful changes in extrapyramidal symptoms, weight gain, or somnolence were observed between treatment groups. Xanomeline-trospium was associated with a significantly greater reduction in positive symptoms compared to placebo. The findings support the potential of xanomeline-trospium as a new class of antipsychotics with a different mechanism of action, targeting muscarinic receptors and not associated with the adverse effects of dopamine receptor antagonists, such as extrapyramidal symptoms, weight gain, or somnolence. These results are consistent with previous trials (EMERGENT-1 and EMERGENT-2), reinforcing the efficacy and safety of xanomeline-trospium in schizophrenia. The trial was conducted in accordance with ethical and regulatory standards, and data were analyzed using appropriate statistical methods. Limitations include the short duration of the trial and the absence of an active comparator group. Further long-term studies are needed to assess the durability of the treatment effect and safety.