Maternal Opioid Treatment: Human Experimental Research

大约三分之一的阿片类药物成瘾者是育龄妇女。阿片类药物依赖期间妊娠 提出了一系列复杂的治疗挑战。美沙酮是唯一的维持剂 目前推荐用于妊娠阿片类药物依赖妇女的药物治疗。美沙酮 提供了许多好处相对于持续未经治疗的海洛因成瘾或医疗戒毒，但其使用 在怀孕期间仍然是有争议的，部分原因是新生儿的比例很大， 需要医疗干预和延长住院时间的阿片类药物戒断体征。与非- 药物暴露婴儿、阿片类药物暴露婴儿的新生儿住院时间更长，费用更高， 表现出神经生理和行为上的紊乱据估计，55%-94%的婴儿接触 子宫内的阿片类药物将显示阿片类药物戒断的迹象。丁丙诺啡，一种正在接受FDA审查的新药 用于治疗阿片类药物依赖，据报道， 成年人突然戒断。丁丙诺啡减少新生儿戒断症状的疗效观察 (NAS)在新生儿中，与美沙酮相比，将在阿片类药物依赖的孕妇中进行评估 采用随机、平行组、多中心设计。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一个小组接受了以下培训： 成瘾医学，精神病学，儿科，产科，妇科和对照临床试验已经被 聚集在一起，为受试者提供全面的护理，并为受试者提供严格的科学诚信。 study.约翰霍普金斯研究中心将作为该多中心试验的牵头研究中心，涉及6家美国研究中心和2家 国际化.受试者随机接受等效阿片类药物剂量的美沙酮（N=30）或丁丙诺啡 （N=30）将在整个妊娠期间进行随访。主要结局指标为NAS、总抗戒断 给予的药物和接受治疗的新生儿人数。次要胎儿/新生儿结局指标为： 标准产前测量、无应激试验、生物物理特征和住院时间（天数）。 次要的母体结局指标包括：治疗保留率、客观和主观指标 包括酒精在内的药物使用、全球评估、剂量充足性和安全数据。这将是第一 研究开发具有开展对照试验专业知识的基础设施和研究中心网络， 药物滥用和依赖药物的孕妇的药物治疗。该网络的使用将 确保在难以招募的人群中成功招募研究参与者（即，怀孕 妇女）。

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).