Citrome Leslie, Graham Christine, Simmons Adam, Jiang Ying, Todtenkopf Mark S, Silverman Bernard, DiPetrillo Lauren, Cummings Hannah, Sun Lei, McDonnell David
Department of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, NY, USA.
Alkermes, Inc., Waltham, MA, USA.
Neuropsychiatr Dis Treat. 2021 Sep 9;17:2885-2904. doi: 10.2147/NDT.S313840. eCollection 2021.
Olanzapine effectively treats schizophrenia and bipolar I disorder (BD-I); however, its use is limited by the risk of significant weight gain and metabolic effects. OLZ/SAM, a combination of olanzapine and samidorphan, was recently approved in the United States for the treatment of adults with schizophrenia or BD-I. OLZ/SAM provides the efficacy of olanzapine while mitigating olanzapine-associated weight gain through opioid-receptor blockade. Here, we summarize OLZ/SAM clinical data characterizing pharmacokinetics, antipsychotic efficacy, weight mitigation efficacy, safety, and long-term treatment effects. In an acute exacerbation of schizophrenia, OLZ/SAM and olanzapine provided similar symptom improvements versus placebo at week 4. In stable outpatients with schizophrenia, OLZ/SAM treatment resulted in significantly less weight gain, reducing the risk for clinically significant weight gain and waist circumference increases of ≥5 cm by half, compared with olanzapine at week 24. Based on open-label extension studies, OLZ/SAM is safe and well tolerated for up to 3.5 years of treatment, while maintaining schizophrenia symptom control and stabilizing weight. The olanzapine component of OLZ/SAM was bioequivalent to branded olanzapine (Zyprexa); adjunctive OLZ/SAM had no clinically significant effects on lithium or valproate pharmacokinetics. Additionally, OLZ/SAM had no clinically relevant effect on electrocardiogram parameters in a dedicated thorough QT study. Overall, safety and tolerability findings from clinical studies with OLZ/SAM indicate a similar safety profile to that of olanzapine, with the exception of less weight gain. As OLZ/SAM contains the opioid antagonist samidorphan, it is contraindicated in patients using opioids and in those undergoing acute opioid withdrawal. Clinical trial results from more than 1600 subjects support the use of OLZ/SAM as a new treatment option for patients with schizophrenia or BD-I.
奥氮平可有效治疗精神分裂症和双相 I 型障碍（BD-I）；然而，其使用受到显著体重增加和代谢影响风险的限制。奥氮平/沙米朵芬（OLZ/SAM）是奥氮平和沙米朵芬的组合，最近在美国被批准用于治疗患有精神分裂症或 BD-I 的成人。OLZ/SAM 具有奥氮平的疗效，同时通过阿片受体阻断减轻与奥氮平相关的体重增加。在此，我们总结了 OLZ/SAM 的临床数据，这些数据描述了其药代动力学、抗精神病疗效、体重减轻疗效、安全性和长期治疗效果。在精神分裂症急性加重期，第 4 周时 OLZ/SAM 和奥氮平与安慰剂相比症状改善相似。在稳定的精神分裂症门诊患者中，与第 24 周时的奥氮平相比，OLZ/SAM 治疗导致的体重增加显著减少，将临床显著体重增加和腰围增加≥5 cm 的风险降低了一半。基于开放标签扩展研究，OLZ/SAM 在长达 3.5 年的治疗中是安全且耐受性良好的，同时维持精神分裂症症状控制并稳定体重。OLZ/SAM 中的奥氮平成分与品牌奥氮平（再普乐）生物等效；辅助使用 OLZ/SAM 对锂或丙戊酸盐的药代动力学没有临床显著影响。此外，在一项专门的全面 QT 研究中，OLZ/SAM 对心电图参数没有临床相关影响。总体而言，OLZ/SAM 的临床研究安全性和耐受性结果表明，除体重增加较少外，其安全性与奥氮平相似。由于 OLZ/SAM 含有阿片类拮抗剂沙米朵芬，在使用阿片类药物的患者和正在进行急性阿片类药物戒断的患者中禁用。来自 1600 多名受试者的临床试验结果支持将 OLZ/SAM 作为精神分裂症或 BD-I 患者的一种新治疗选择。
