Edinoff, Wu, Tzoneva, Louisiana State University Health Science Center Shreveport, Department of Psychiatry, and Behavioral Medicine. deBoisblanc, Feltner, Norder, Louisiana State University Shreveport School of Medicine. Kaye, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Department of Pharmacy Practice, Stockton, CA. Cornett, Kaye, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA. Viswanath, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, Creighton University School of Medicine, Department of Anesthesiology, Omaha, NE, Valley Anesthesiology and Pain Consultants - Envision Physician Services, Phoenix, AZ. Urits, Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA. Beth Israel Deaconess Medical Center, Department of Anesthesiology, Critical Care, and Pain Medicine, Harvard Medical School, Boston, MA.
Psychopharmacol Bull. 2020 Sep 14;50(4):32-59.
Schizophrenia is a severe psychotic disorder that is diagnosed by the presence of hallucinations or delusions along with disorganized speech, disorganized thought, or negative symptoms that are present for at least six months. Roughly 1 in 10,000 people a year are diagnosed with this psychiatric disorder. It is a chronic disorder requiring a lifetime of treatment of which antipsychotics have been the mainstay of this treatment. First-generation antipsychotics have dystonia, parkinsonism, and development of Tardive Dyskinesia as major side effects, and they are also nonspecific in terms of their actions. Second Generation antipsychotics target more specific dopamine and sometimes serotonin receptors with less dystonic side effects; however, there are additional concerns for the development of metabolic syndrome. This review aims to look at new medication on the market, lumateperone, for the treatment of Schizophrenia.
In one four week study with 60mg and 120mg of Lumateperone compared, 4mg of Risperdal, and a placebo found that Lumateperone significantly decreased the total Positive and Negative Syndrome Scale (PANSS) from baseline. Safety analysis of this study also found that Lumateperone was not associated with EPS or significant weight gain. Another study found that 42mg of Lumateperone significantly decreased PANSS score over placebo and 28mg of Lumateperone with associated TEAEs of somnolence, sedation, fatigue, and constipation. In an open-label safety, patients were switched from their current antipsychotic to Lumateperone and then switched back to their previous treatment after six weeks. PATIENTS were found to have statistically significant improvements in metabolic parameters, weight, and endocrine parameters, which were all lost when they were switched back to their previous treatment and their schizophrenic symptoms at pre-trial levels or improved them while on Lumateperone. In a continuation of the previous study over 12 months, 4 TEAEs occurred in 5% or more of the participants: diarrhea, dry mouth, weight decrease, and headache. Prolactin, metabolic labs, BMI, and weight all decreased as compared to the standard of care. Pooled studies revealed EPS related TEAEs were less frequent in patients receiving 42 mg lumateperone over Risperdal. Another pooled study looked at the safety profile; they found patients treated with lumateperone, two TEAEs occurred at twice the placebo rate and at a rate of 5% or more: dry mouth (5% vs. 2.2%) and sedation (24.1% vs. 10.0%) though TEAE discontinuation rates were lower than with Risperdal.
Taken together, data from these trials suggest that lumateperone can effectively treat positive symptoms, negative symptoms, and cognitive dysfunction in schizophrenia. Lumateperone entrance to the market introduces an innovative way to treat schizophrenia featuring both a novel mechanism of action and a markedly reduced side effect profile. Further research is needed to determine the efficacy of Lumateperone in treating bipolar disorder in addition to schizophrenia.
精神分裂症是一种严重的精神障碍，其诊断标准为存在幻觉或妄想，以及言语紊乱、思维紊乱或阴性症状，这些症状至少持续六个月。每年大约有 1/10000 的人被诊断出患有这种精神疾病。它是一种需要终身治疗的慢性疾病，其中抗精神病药一直是治疗的主要方法。第一代抗精神病药有肌张力障碍、帕金森病和迟发性运动障碍等主要副作用，而且它们的作用也不具有特异性。第二代抗精神病药针对多巴胺和有时是 5-羟色胺受体，副作用较小；然而，它们也存在代谢综合征发展的额外问题。本综述旨在研究市场上的新药物，即鲁拉西酮，用于治疗精神分裂症。
在一项为期四周的研究中，将 60mg 和 120mg 的鲁拉西酮与 4mg 的利培酮和安慰剂进行了比较，结果发现鲁拉西酮能显著降低阳性和阴性综合征量表（PANSS）的总分。这项研究的安全性分析还发现，鲁拉西酮与 EPS 或明显体重增加无关。另一项研究发现，42mg 的鲁拉西酮与安慰剂相比显著降低了 PANSS 评分，而 28mg 的鲁拉西酮与嗜睡、镇静、疲劳和便秘等治疗相关不良事件相关。在一项开放性安全性研究中，患者从目前的抗精神病药物转换为鲁拉西酮，然后在六周后转回之前的治疗。结果发现，患者的代谢参数、体重和内分泌参数都有统计学意义的改善，当他们转回之前的治疗时，这些参数都丢失了，而在使用鲁拉西酮时则有所改善。在之前研究的 12 个月的延续中，5%或更多的参与者出现了 4 种治疗相关不良事件：腹泻、口干、体重下降和头痛。与标准治疗相比，催乳素、代谢实验室、BMI 和体重均有所下降。汇总研究显示，接受 42mg 鲁拉西酮治疗的患者 EPS 相关治疗相关不良事件的频率低于利培酮。另一项汇总研究观察了安全性概况；他们发现，接受鲁拉西酮治疗的患者有两种治疗相关不良事件的发生率是安慰剂的两倍，发生率为 5%或更高：口干（5%比 2.2%）和镇静（24.1%比 10.0%），但与利培酮相比，治疗相关不良事件的停药率较低。
综上所述，这些试验的数据表明，鲁拉西酮可以有效治疗精神分裂症的阳性症状、阴性症状和认知功能障碍。鲁拉西酮进入市场为治疗精神分裂症提供了一种创新的方法，具有新颖的作用机制和明显减少的副作用特征。需要进一步研究来确定鲁拉西酮在治疗双相情感障碍方面除了精神分裂症之外的疗效。
