Pham Huy, Warlick Halford, Bermudez Ricardo, Nguyen Quan, Rey Jose A
Nova Southeastern University College of Pharmacy, Davie, FL, USA.
Nova Southeastern University College of Osteopathic Medicine, Davie, FL, USA.
J Pharm Technol. 2022 Oct;38(5):304-313. doi: 10.1177/87551225221114281. Epub 2022 Jul 29.
To review the pharmacology, pharmacokinetics, and efficacy and safety data of a combination of olanzapine and samidorphan (OLZ/SAM) for the treatment of schizophrenia and bipolar I disorder, which mitigates the possible unwanted side effects of weight gain associated with olanzapine (OLZ).
The review was done with a bibliographic survey of studies using MEDLINE/PubMed (January 1999-May 2021) database using the keywords olanzapine and samidorphan. Abstracts, scientific posters, and information from the manufacturer's product labeling were evaluated for inclusion. Inclusion criteria: phase 2, phase 3, and open-labeled studies that evaluated the use of OLZ/SAM for the treatment of schizophrenia and bipolar I disorder.
We have included one phase 2 dose-ranging exploratory study, two phase 3 efficacy and safety studies, and several open-label extension studies without a comparator. For the treatment of schizophrenia, OLZ/SAM and OLZ alone were analyzed in 2 randomized, double-blind comparison studies of approximately 960 patients. Analysis indicated that OLZ (5-20 mg)/SAM (10 mg) significantly mitigated the side effect of weight gain compared with OLZ alone (control) while maintaining antipsychotic efficacy. For bipolar I disorder, OLZ/SAM was approved as an acute treatment for manic or mixed episodes, as well as an adjunct to valproate or lithium for manic/mixed episodes based on bridging strategy allowed by the Food and Drug Administration.
The combination of olanzapine and samidorphan demonstrated efficacy for the treatment of schizophrenia with a dosage range of 5 to 20 mg OLZ to a 10-mg fixed dose of samidorphan. Advantages of this drug combination include once-daily dosing, favorable tolerability, and most importantly, mitigation of weight gain, which may encourage adherence, when compared with OLZ alone.
The new combination treatment of OLZ/SAM is a unique antipsychotic formulation to provide the recognized efficacious treatment of OLZ, while mitigating the weight gain and possibly the weight-related adverse effects secondary to OLZ monotherapy.
综述奥氮平与沙米朵芬（OLZ/SAM）联合用药治疗精神分裂症和双相I型障碍的药理学、药代动力学、疗效及安全性数据，该联合用药可减轻奥氮平（OLZ）可能带来的体重增加等不良副作用。
通过使用MEDLINE/PubMed（1999年1月至2021年5月）数据库，以奥氮平和沙米朵芬为关键词进行文献检索，对检索到的研究进行综述。对摘要、科学海报以及来自制造商产品标签的信息进行评估以确定是否纳入。纳入标准：评估OLZ/SAM用于治疗精神分裂症和双相I型障碍的2期、3期及开放标签研究。
我们纳入了一项2期剂量范围探索性研究、两项3期疗效和安全性研究以及几项无对照的开放标签扩展研究。对于精神分裂症的治疗，在两项约960例患者的随机、双盲对照研究中分析了OLZ/SAM和单用OLZ的情况。分析表明，与单用OLZ（对照）相比，OLZ（5 - 20 mg）/SAM（10 mg）在维持抗精神病疗效的同时，显著减轻了体重增加的副作用。对于双相I型障碍，根据美国食品药品监督管理局允许的桥接策略，OLZ/SAM被批准用于躁狂或混合发作的急性治疗，以及作为丙戊酸盐或锂盐治疗躁狂/混合发作的辅助药物。
奥氮平与沙米朵芬联合用药在OLZ剂量范围为5至20 mg、SAM固定剂量为10 mg时，对精神分裂症的治疗显示出疗效。这种药物组合的优点包括每日一次给药、耐受性良好，最重要的是，与单用OLZ相比，减轻了体重增加，这可能会提高患者的依从性。
OLZ/SAM这种新的联合治疗方法是一种独特的抗精神病制剂，在提供OLZ公认的有效治疗的同时，减轻了体重增加以及可能由OLZ单药治疗引起的与体重相关的不良反应。
