Relapse risk after Discontinuation of Antidepressants during Pregnancy (R-DAP study)

怀孕期间停用抗抑郁药后复发的风险（R-DAP 研究）

• 批准号: 10569044
• 负责人: Veerle Bergink
• 金额: $ 55.2万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-02 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10569044
• 关键词: Adverse effects; Antidepressive Agents; Anxiety Disorders; Bipolar Disorder; Birth; Child; Conceptions; Decision Making; Depressive disorder; Emotions; Endocrine; Event; Exposure to; Fathers; Female; Fetal Development; Fetus; General Population; Genetic; Genetic Predisposition to Disease; Genetic study; Goals; Health; Immune; Investigation; Life; Long-Term Effects; Mental Depression; Mental Health; Mental disorders; Mood Disorders; Moods; Mothers; Outcome; Outpatients; Perinatal; Pharmaceutical Preparations; Physiology; Population; Postpartum Period; Pregnancy; Pregnant Women; Process; Psychiatric therapeutic procedure; Relapse; Reporting; Residual state; Resources; Risk; Risk Factors; Risk Reduction; Sample Size; Sampling; Schizophrenia; Self-Injurious Behavior; Severities; Siblings; Sleep Deprivation; Suicide; Suicide attempt; Time; Woman; Work; aged; antidepressant effect; genetic information; health of the mother; in utero; interest; maternal depression; men; offspring; perinatal period; peripartum depression; pharmacologic; polygenic risk score; population based; predictive modeling; prenatal exposure; relapse risk; reproductive; secondary outcome; tool; unborn child

Project Summary Over the past decades, the use of antidepressants (ADs) as first-line treatment for both depressive and anxiety disorders has increased exponentially, with females in their reproductive years using ADs twice as often as men. Prior to conception or during pregnancy, approximately 50% of women on ADs (200,000 pregnant women in the US each year) decide to discontinue their medication. While the wish to avoid in utero AD exposure to the fetus is understandable, discontinuation of medication might lead to relapse, which can have a profound negative impact on the health of mother and child. Unfortunately, general information on relapse risks after AD discontinuation cannot be used during pregnancy and the postpartum period given the enormous changes in physiology and emotion. Further, women discontinue AD prior to or during pregnancy regardless of their mood stability, which has an impact on relapse risk. Only three small studies in highly selected populations have investigated relapse risks during pregnancy and not a single study on AD discontinuation during pregnancy has investigated the relapse risk postpartum. This study will quantify the relapse risk during pregnancy and postpartum after AD discontinuation, for the first time, in a large and representative population sample. We will use the unique Danish national longitudinal registers covering medication use since 1995 in the entire female population giving birth aged 15-49 years (N=1,098,137). With our sample size, we will be able to identify both pregnancy specific and non-pregnancy specific risk factors for relapse and timing to relapse. We will determine to which extent the perinatal period is different in terms of relapse risks after AD discontinuation compared to other periods in a woman’s life. In addition, we will explore if women with high genetic susceptibility for mood-disorders are more vulnerable for relapse after AD discontinuation. In our last aim we will determine the long-term effects (up to 24 years) of maternal relapse during pregnancy and the postpartum period on the offspring. We will conduct a sibling comparison, in which we compare the health outcomes in children exposed to maternal relapse to their siblings not exposed to maternal relapse in the perinatal period. We will explore if polygenic risk scores of the children influence the association between their exposure to maternal relapse and their long-term psychiatric outcome, considering in utero exposure to AD medication.

项目摘要 在过去的几十年里，抗抑郁药（AD）作为抑郁和焦虑的一线治疗药物， 疾病呈指数增长，女性在生育年龄使用AD的频率是男性的两倍。 在怀孕前或怀孕期间，大约50%的服用AD的妇女（200，000名孕妇） 美国每年）决定停止他们的药物。虽然希望避免胎儿在子宫内接触AD 是可以理解的，停药可能会导致复发，这可能会产生深远的负面影响。 对母婴健康的影响。不幸的是，关于AD后复发风险的一般信息 怀孕期间和产后期间不能使用停药，因为 生理和情感此外，妇女在怀孕前或怀孕期间停止AD，无论其情绪如何 稳定性，这对复发风险有影响。只有三个在高度选择的人群中进行的小型研究 研究了妊娠期间的复发风险，没有一项关于妊娠期间停用AD的研究 调查产后复发风险。 本研究将量化妊娠期间和AD停药后产后的复发风险， 第一次，在一个大的和有代表性的人口样本。我们将使用独特的丹麦国家纵向 1995年以来15-49岁生育妇女使用药物情况登记册 （N= 1 098 137）。根据我们的样本量，我们将能够识别妊娠特异性和非妊娠 复发的特定风险因素和复发时间。我们将确定围产期在多大程度上是 与女性生命中的其他时期相比，AD停药后的复发风险不同。在 此外，我们还将探讨情绪障碍遗传易感性高的女性是否更容易受到 AD停药后复发。在我们的最后一个目标中，我们将确定以下因素的长期影响（长达24年）： 母亲在怀孕期间和产后期间复发对后代的影响。我们会让一个兄弟姐妹 比较，我们将暴露于母亲复发的儿童的健康结果与其兄弟姐妹进行比较 在围产期没有暴露于母体复发。我们将探讨儿童的多基因风险评分 影响他们暴露于母亲复发和他们的长期精神病结果之间的关联， 考虑到子宫内暴露于AD药物