Comparative Effectiveness and Safety of Depression Treatments during Pregnancy

描述（由申请人提供）：抑郁症影响了所有孕妇的10-15%，其中许多人使用抗抑郁药治疗，如选择性血清素再摄取抑制剂（SSRIs）。然而，多项研究表明，产前暴露于SSRIs与心血管畸形、新生儿持续性肺动脉高压和新生儿戒断综合征风险增加之间存在关联。另一方面，与继续服用抗抑郁药的孕妇相比，停止服用抗抑郁药的重度抑郁症孕妇更容易出现症状复发。由于中度至重度抑郁症需要药物治疗，而且许多怀孕是计划外的，因此临床相关的问题是：1)向育龄妇女推荐哪种抗抑郁药或SSRI； 2)怀孕期间是否以及何时停止治疗。尽管患者和医生面临着困难的决定，但缺乏足够的相对安全性和有效性信息来指导怀孕期间抑郁症的治疗决策。我们的主要目标是提供直接证据，证明每种抗抑郁药在弱势人群（即低收入抑郁孕妇及其子女）中的相对有效性和安全性。我们假设并不是所有的SSRIs都是一样的，在怀孕早期停止可能会降低治疗的有效性，同时降低一些风险。我们建议量化与妊娠期间继续和停止使用特定SSRIs相关的母体和胎儿不良事件的风险。在医疗补助分析提取（MAX）中，一个大型的基于人口的索赔数据库，可链接到额外的产科、分娩和精神病学记录，我们将确定一个超过78,000名在2001年至2007年间分娩的孕前服用SSRIs的妇女队列。我们将比较妊娠期间继续和停止使用特定SSRIs的有效性和安全性。我们将采用倾向评分技术和嵌套病例控制分析的创新组合，并将从医疗记录中获取信息，以验证结果，并纳入详细的临床信息，包括抑郁症严重程度的测量。目前的提案是布里格姆妇女医院药物流行病学和药物经济学部门、哈佛大学公共卫生学院流行病学部门和马萨诸塞州总医院围产期精神病学项目之间的跨学科合作。

DESCRIPTION (PROVIDED BY APPLICANT): Depression affects 10-15% of all pregnant women and many of them are treated with antidepressants such as selective serotonin reuptake inhibitors (SSRIs). However, multiple studies have suggested an association between prenatal exposure to SSRIs and an increased risk of cardiovascular malformations, persistent pulmonary hypertension of the newborn and neonatal withdrawal syndrome. On the other hand, pregnant women with major depression who discontinue antidepressant therapy experience relapse of symptoms more often than those who continue on antidepressants. Because moderate to severe depression require pharmacologic treatment and many pregnancies are unplanned, the clinically relevant questions are 1) which antidepressant or SSRI 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 comparative safety and effectiveness information to guide therapeutic decisions for depression during pregnancy is lacking. Our primary objective is to provide direct evidence on the comparative effectiveness and safety of each antidepressant in a vulnerable segment of the population, i.e., low income depressed pregnant women and their children. We hypothesize that not all SSRIs are equal and that discontinuation early in pregnancy might reduce the effectiveness of treatment while reducing some risks. We propose to quantify the risk of maternal and fetal adverse events associated with continuing and discontinuing specific SSRIs during pregnancy. Within the Medicaid Analytic eXtract (MAX), a large population-based claims database linkable to additional obstetrical, birth, and psychiatric records, we will identify a cohort of over 78,000 women on SSRIs before conception who delivered between 2001 and 2007. We will compare the effectiveness and safety of continuing versus discontinuing specific SSRIs during pregnancy. We will apply an innovative combination of propensity score techniques and nested case control analyses and will obtain information from medical records to validate the outcomes and incorporate detailed clinical information, including measures of depression severity. The current proposal is an interdisciplinary collaboration between the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women's Hospital, the Department of Epidemiology at Harvard School of Public Health, and the Perinatal Psychiatry Program at Massachusetts General Hospital.