Efficacy, safety, and tolerability of xanomeline for schizophrenia spectrum disorders: a systematic review
Alexia Leber, Ranuk Ramachandra, Felicia Ceban, Angela T.H. Kwan, Taeho Greg Rhee, Jie Wu, Bing Cao, Muhammad Youshay Jawad, Kayla M. Teopiz, Roger Ho, Gia Han Le, Diluk Ramachandra, Roger S. McIntyre
Abstract
Introduction We systematically reviewed extant studies evaluating the efficacy and tolerability of xanomeline and xanomeline-trospium (KarXT) for treatment of adults with schizophrenia.Methods In accordance with PRISMA guidelines, articles were systematically searched for in databases and clinical trial registries.Results 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.Conclusion KarXT offers an innovative non-D2 blocking approach, representing a promising treatment avenue for schizophrenia.