Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
Brain and Cognition Discovery Foundation, Toronto, ON, Canada.
Curr Psychiatry Rep. 2022 Aug;24(8):359-368. doi: 10.1007/s11920-022-01344-1. Epub 2022 Jul 8.
Lumateperone (LUM) is the U.S. Food and Drug Administration approved atypical antipsychotic agent for adults with schizophrenia (SCZ) and bipolar depression (for both bipolar I and bipolar II disorder as as monotherapy or as adjunctive treatment to lithium or valproate). LUM simultaneously modulates serotonin, dopamine, and glutamate neurotransmission. The foregoing pleiotropic mechanism of action is predictive of therapeutic benefits across multiple domains of psychopathology in SCZ (i.e., positive, negative, cognitive, and prosocial symptoms). Herein, the overarching aim is to synthesize the extant literature reporting on the efficacy, safety, and tolerability of LUM in adults with SCZ.
Four clinical studies (i.e., three RCTs and one open-label trial) were included in this synthesis. Overall, LUM significantly reduced the severity of SCZ compared with placebo. The open label study provided the real-world effectiveness of shifting stable patients with SCZ to LUM from other atypical antipsychotics. With respect to safety and tolerability profile, LUM demonstrated placebo-level rates of weight gain, metabolic shift, prolactin elevation, extrapyramidal side effects (EPS), and akathisia across short term trials (i.e., 4-6 weeks). Taken together, our results indicate that LUM significantly improves symptoms severity in adults with SCZ. LUM also exhibits a favorable tolerability and safety profile with placebo level rates of weight gain, metabolic disruption, akathisia, extrapyramidal side effects (excluding akathisia), and prolactin elevation. Lumateperone should be conceptualized as a first-line treatment strategy for adults with SCZ.
鲁玛特酮（LUM）是美国食品和药物管理局批准的用于治疗成人精神分裂症（SCZ）和双相情感障碍抑郁发作（包括双相 I 型和双相 II 型障碍，作为单药治疗或作为锂或丙戊酸盐的辅助治疗）的新型抗精神病药。LUM 同时调节 5-羟色胺、多巴胺和谷氨酸神经递质。上述多效作用机制预测 LUM 在 SCZ 的多个精神病理学领域（即阳性、阴性、认知和亲社会症状）具有治疗益处。在此，总体目标是综合现有文献报告 LUM 治疗成人 SCZ 的疗效、安全性和耐受性。
本综述纳入了四项临床研究（即三项 RCT 和一项开放标签试验）。总体而言，与安慰剂相比，LUM 显著降低了 SCZ 的严重程度。开放标签研究提供了将稳定的 SCZ 患者从其他非典型抗精神病药转换为 LUM 的真实世界疗效。关于安全性和耐受性，LUM 在短期试验（即 4-6 周）中显示出与安慰剂相似的体重增加、代谢变化、催乳素升高、锥体外系副作用（EPS）和静坐不能的发生率。综上所述，我们的结果表明 LUM 显著改善了成人 SCZ 的症状严重程度。LUM 还具有良好的耐受性和安全性，体重增加、代谢紊乱、静坐不能、锥体外系副作用（不包括静坐不能）和催乳素升高的发生率与安慰剂相似。鲁玛特酮应被视为成人 SCZ 的一线治疗策略。
