Maternal Opioid Treatment: Human Experimental Research

大约三分之一的阿片成瘾者是育龄妇女。阿片类药物依赖期妊娠 提出了一系列复杂的治疗挑战。美沙酮是唯一的维持剂 目前推荐用于怀孕的阿片依赖妇女的药物治疗。美沙酮 与持续的未经治疗的海洛因成瘾或药物戒毒相比，提供了许多好处，但它的使用 怀孕期间继续存在争议，部分原因是有很大比例的新生儿患有 阿片类药物戒断的迹象需要医疗干预和延长住院时间。与非 接触药物的婴儿、接触阿片的婴儿的新生儿住院时间更长、费用更高 显示出神经生理和行为障碍。据估计，55%-94%的婴儿暴露在 子宫内的阿片类药物会显示出阿片类药物戒断的迹象。正在接受FDA审查的新药丁丙诺啡 用于治疗阿片类药物依赖，据报道只会产生轻微的戒断症状 成年人的突然戒断。丁丙诺啡减少新生儿禁欲症状的疗效观察 将在阿片类药物依赖孕妇中评估新生儿(NAS)与美沙酮的比较 采用随机、平行分组、多点设计。多学科的专业知识 范德比尔特大学医学中心和田纳西州中部治疗中心的小组在 成瘾药物、精神病学、儿科、产科、新生儿科和对照临床试验 汇聚在一起，为受试者提供全面的关怀和严格的科学诚信 学习。约翰霍普金斯大学的站点将作为这项涉及六个美国站点和两个站点的多站点试验的牵头站点 国际的。受试者随机接受同等剂量的美沙酮(N=30)或丁丙诺啡治疗 (n=30)将在整个妊娠期间进行随访。主要结果指标是NAS，全面反撤资 给予的药物，以及治疗的新生儿数量。二次胎儿/新生儿结局衡量标准为： 标准产前检查、无应激试验、生物物理资料和住院天数。 次级孕产妇结果衡量标准包括：治疗保留率、客观和主观标准 包括酒精在内的药物使用情况、全球评估、剂量充分性和安全性数据。这将是第一次 研究开发具有进行对照试验的专门知识的基础设施和站点网络 药物滥用和依赖孕妇的药物治疗。该网络的利用率将 确保研究参与者在难以招募的人群(即怀孕)中成功获得收益 女性)。

Approximately 1/3 of opioid addicts are women of childbearing age. Pregnancy during opioid dependence presents a complex array of therapeutic challenges. Methadone is the only maintenance pharmacotherapy currently recommended for use in pregnant opioid-dependent women. Methadone offers many benefits relative to continued untreated heroin addiction or medical detoxification, but its use during pregnancy continues to be controversial due in part to the large percentage of newborns having signs of opioid withdrawal requiring medical intervention and extended hospitalization. Compared to non- drug exposed infants, opioid exposed infants have longer and more costly neonatal hospitalizations and display neurophysiological and behavioral disruptions. It is estimated that 55%-94% of infants exposed to opioids in utero will show signs of opioid withdrawal. Buprenorphine, a new medication under FDA review for the treatment of opioid dependence, is reported to produce only a mild abstinence syndrome following abrupt withdrawal in adults. The efficacy of buprenorphine to produce less neonatal abstinence signs (NAS) in the neonate, compared to methadone, will be assessed in opioid-dependent pregnant women utilizing a randomized, parallel group, multi-site design. The professional expertise of a multi-disciplinary group at Vanderbilt University Medical Center and Middle Tennessee Treatment Center trained in addiction medicine, psychiatry, pediatrics, obstetrics, neonatology, and controlled clinical trials has been brought together to provide comprehensive care for the subjects and rigorous scientific integrity for the study. The Johns Hopkins site will act as the Lead Site of this multi-site trial involving six US sites and two International. Subjects randomized to equivalent opioid doses of methadone (N=30) or buprenorphine (N=30) will be followed through pregnancy. Primary outcome measures are NAS, total anti-withdrawal medication given, and number of neonates treated. Secondary fetal/neonatal outcome measures are: standard antenatal measures, non-stress test, biophysical profile, and length (days) of hospital stay. Secondary maternal outcome measures include: treatment retention, objective and subjective measures of drug use including alcohol, global assessments, dose-adequacy and safety data. This will be the first study to develop an infrastructure and network of sites with expertise in conducting controlled trials with pharmacotherapies for substance abusing and dependent pregnant women. Utilization of this network will ensure the successful accrual of study participants in a difficult to recruit population (i.e., pregnant women).