Comparative Safety of commonly prescribed Psychotropic Drugs in pregnant Women

摘要 精神疾病使超过15%的怀孕复杂化。这些疾病中的许多需要用 精神药物。然而，多项研究表明，产前暴露于 精神药物和重大畸形、生长受限、新生儿戒断的风险增加 新生儿的综合症和呼吸问题，以及妊娠期糖尿病、先兆子痫和 在母亲的剖腹产。另一方面，患有精神和/或神经疾病的孕妇 中断治疗的病情可能会复发，这些症状对他们来说可能是危险的 他们的后代。因为其中许多情况需要药物治疗，许多怀孕需要药物治疗 出乎意料的是，临床上相关的问题是1)为女性推荐哪种特定的药物 生育年龄和2)是否以及何时停止孕期治疗。尽管困难重重 患者和医生面临的决定，足够的信息来指导治疗建议 在怀孕期间缺乏精神药物的使用。即使这些药物可能是安全的，但缺乏 对知识的了解可能会给孕妇带来不必要的焦虑。我们的主要目标是提供 直接证据表明，用于治疗情绪障碍、精神病、 和注意缺陷多动障碍(ADHD)在一群孕妇中，包括 易受伤害的贫穷年轻女性。我们假设并不是所有的毒品都是平等的，风险-收益交易- 妊娠期间是否继续治疗因药物不同而不同。我们建议将母婴传播的风险量化 与继续和停用特定精神药物有关的胎儿不良事件 怀孕了。在医疗补助分析摘录(MAX)和UnitedHealth Research数据库中，有两个 大型基于人群的索赔数据库可以链接到额外的产科、出生和精神疾病记录，我们 将确定超过18,500名服用情绪稳定剂(抗癫痫药)的女性，6,500名服用抗精神病药物的女性，以及 在2000至2012年间分娩的受孕者中，有3000人服用精神刺激剂。相对风险和95% 将使用考虑了可能的相关性的回归模型来计算可信区间 由多胎妊娠引起的。我们将应用高维倾向分数的创新组合 技术、工具变量和外部调整，以最大限度地减少混淆的可能性 贝叶斯方法来解释先验信息并支持患者亚组分析。我们将获得 来自医疗记录的信息以验证特定结果和来自国家健康和营养部门的信息 检查调查，以获取有关吸烟、酒精和酒精等潜在混杂因素的信息 肥胖。目前的提议是布里格姆医院和妇女医院之间的跨学科合作 以及哈佛大学公共卫生学院的流行病学系。

ABSTRACT Mental illnesses complicate over 15% of all pregnancies. Many of these conditions require treatment with psychotropic drugs. However, multiple studies have suggested an association between prenatal exposure to psychotropic drugs and an increased risk of major malformations, growth restriction, neonatal withdrawal syndrome and respiratory problems in the newborn, as well as gestational diabetes, preeclampsia and cesarean section in the mother. On the other hand, pregnant women with mental and/or neurological conditions who discontinue therapy may experience relapse of symptoms that can be dangerous for them and their offspring. Because many of these conditions require pharmacologic treatment and many pregnancies are unplanned, the clinically relevant questions are 1) which specific medication to recommend for women of childbearing age and 2) whether and when to discontinue treatment during pregnancy. Despite the difficult decisions faced by patients and physicians, sufficient information to guide therapeutic recommendations for the use of psychotropic drugs during pregnancy is lacking. Even when these medications may be safe, the lack of knowledge may instill unnecessary anxiety in pregnant women. Our primary objective is to provide direct evidence on the comparative safety of specific strategies used to manage mood disorders, psychosis, and attention deficit hyperactivity disorders (ADHD) in a population of pregnant women, which includes vulnerable indigent young women. We hypothesize that not all drugs are equal and that the risk-benefit trade- off of continuing treatment during pregnancy will differ by drug. We propose to quantify the risk of maternal and fetal adverse events associated with continuing and discontinuing specific psychotropic drugs during pregnancy. Within both the Medicaid Analytic eXtract (MAX) and the UnitedHealth Research database, two large population-based claims databases linkable to additional obstetrical, birth, and psychiatric records, we will identify cohorts of over 18,500 women on mood stabilizers (antiepileptics), 6,500 on antipsychotics, and 3,000 on psychostimulants at conception who delivered between 2000 and 2012. Relative risks and 95% confidence intervals will be calculated using regression models that account for the possible correlation induced by multiple gestations. We will apply an innovative combination of high dimensional propensity score techniques, instrumental variables and external adjustment to minimize the potential for confounding, and Bayesian approaches to account for prior information and support patient subgroup analyses. We will obtain information from medical records to validate specific outcomes and from the National Health and Nutrition Examination Survey to obtain information on potential confounders such as smoking, alcohol and obesity. The current proposal is an interdisciplinary collaboration between the Brigham and Women's Hospital and the Department of Epidemiology at Harvard School of Public Health.