Efficacy, safety, and tolerability of xanomeline for schizophrenia spectrum disorders: a systematic review

We systematically reviewed extant studies evaluating the efficacy and tolerability of xanomeline and xanomeline-trospium (KarXT) for treatment of adults with schizophrenia. In accordance with PRISMA guidelines, articles were systematically searched for in databases and clinical trial registries. A total of 4 preclinical trials and 3 randomized controlled trials (RCTs) were included in this review. A 4-week RCT observed a difference of 24.0 points (SD 21.0) in the Positive and Negative Syndrome Scale (PANSS) total score between xanomeline and placebo groups (p = 0.039). A 5-week RCT observed PANSS total score changes from baseline to week 5, including −17.4 and −5.9 points in KarXT and placebo groups, respectively (LSMD −11.6 points; 95% CI −16.1 to −7.1; p < 0.001; d = 0.75). Another 5-week RCT observed PANSS total score changes from baseline to week 5, including −21.2 (SE 1.7) and −11.6 (SE 1.6) points in KarXT and placebo groups, respectively (LSMD −9.6; 95% CI −13.9 to −5.2; p < 0.0001; d = 0.61). Side effects include constipation, nausea, vomiting, dyspepsia, and dry mouth. KarXT offers an innovative non-D2 blocking approach, representing a promising treatment avenue for schizophrenia.