Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.
Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada.
Expert Opin Pharmacother. 2024 Mar;25(4):467-476. doi: 10.1080/14656566.2024.2334424. Epub 2024 Mar 27.
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 ( = 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; < 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; < 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.
我们系统地回顾了评估 xanomeline 和 xanomeline-trospium（KarXT）治疗成人精神分裂症的疗效和耐受性的现有研究。
根据 PRISMA 指南，系统地在数据库和临床试验注册库中搜索文章。
本综述共纳入 4 项临床前试验和 3 项随机对照试验（RCT）。一项为期 4 周的 RCT 观察到 xanomeline 组和安慰剂组之间阳性和阴性综合征量表（PANSS）总分的差异为 24.0 分（SD 21.0）（ = 0.039）。一项为期 5 周的 RCT 观察到从基线到第 5 周的 PANSS 总分变化，KarXT 组和安慰剂组分别为-17.4 和-5.9 分（LSMD -11.6 分；95%CI -16.1 至 -7.1； < 0.001；d = 0.75）。另一项为期 5 周的 RCT 观察到从基线到第 5 周的 PANSS 总分变化，KarXT 组和安慰剂组分别为-21.2（SE 1.7）和-11.6（SE 1.6）分（LSMD -9.6；95%CI -13.9 至 -5.2； < 0.0001；d = 0.61）。副作用包括便秘、恶心、呕吐、消化不良和口干。
KarXT 提供了一种创新的非 D2 阻断方法，代表了精神分裂症治疗的一个有前途的途径。
