Optimizing Pharmacotherapy for Depression during Pregnancy (OPTI-MOM)

优化妊娠期抑郁症药物治疗 (OPTI-MOM)

• 批准号: 9119071
• 负责人: Alfred L. George
• 金额: $ 77.93万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9119071
• 关键词: Abstinence Syndrome; Accounting; Adverse effects; Antidepressive Agents; Biological Markers; Birth; CYP2C19 gene; CYP2D6 gene; CYP3A4 gene; Cessation of life; Characteristics; Citalopram; Clinical Research; Collaborations; Country; Cytochromes; Data; Development; Discipline of obstetrics; Dose; Drug Kinetics; Drug toxicity; Effectiveness; Environment; Escitalopram; Evaluation; Fluoxetine; Frequencies; Genes; Genetic; Genomics; Genotype; Goals; Guidelines; Illinois; Individual; Individual Differences; Isoenzymes; Laws; Left; Literature; Major Depressive Disorder; Medication Management; Mental Depression; Metabolism; Mothers; Neonatal; Neonatal Abstinence Syndrome; Netherlands; Neuraxis; New Jersey; New York; Newborn Infant; Observational Study; Obstetric Fetal Pharmacology; Outcome; P-Glycoprotein; Patients; Perinatal; Pharmaceutical Preparations; Pharmacodynamics; Pharmacogenetics; Pharmacogenomics; Pharmacology; Pharmacotherapy; Pilot Projects; Plasma; Postpartum Period; Postpartum Women; Pregnancy; Pregnancy Complications; Pregnant Women; Psychiatry; Psychopharmacology; Regimen; Research; Research Infrastructure; Research Project Grants; Risk; Safety; Selective Serotonin Reuptake Inhibitor; Sertraline; Suicide; Third Pregnancy Trimester; Time; Translational Research; Treatment Efficacy; United States; Woman; World Health Organization; anxiety symptoms; burden of illness; depressive symptoms; effective therapy; efficacy testing; fetal; hazard; interdisciplinary approach; medical complication; metabolic phenotype; mortality; peripartum depression; postnatal; public health priorities; public health relevance; reproductive; response; screening; tool

 DESCRIPTION (provided by applicant): Major Depressive Disorder is one of the most common complications of pregnancy, with 7.5% of women having an incident episode during the 9 months of pregnancy and 6.5% with an episode in the first 3 months postpartum. The overarching goal in this OPRC submission is to develop guidelines to optimize the safety and effectiveness of SSRI antidepressant treatment in pregnant women. This application responds to several priorities from the OPRC RFA, including establishing interdisciplinary approaches to understand the pharmacokinetics and/or pharmacodynamics of medications. The PI team includes Katherine L. Wisner, MD MS (psychiatry); Catherine Stika, MD (obstetrics), and Alfred George, MD (pharmacogenomics). The Administrative Core will provide the infrastructure for collaboration with the OPRC network and within the 3 main OPTI-MOM projects identified below, which have strong complementarity: 1. The Clinical Research Project. -Assess the safety and toxicity of drugs during pregnancy and the postpartum periods. The progressive changes in plasma SSRI and metabolite concentrations across pregnancy and after birth will be determined in an observational study. Serial evaluations of depressive and anxiety symptoms and side effects will be obtained to evaluate their association with plasma concentrations at monthly intervals during pregnancy and twice post-birth. To assess the subjects' metabolic phenotypes, a probe drug cocktail will be given to evaluate the activities of CYP2D6, 2C19, 2C9 and 3A4 during the third trimester (when activity change is maximal) compared to the non-pregnant state after birth. 2. The Basic/Translational Research Project -Perform clinical research to understand mechanisms of pregnancy related changes in drug response and disposition and --Identify biomarkers for safe and effective treatment of pregnancy-related conditions. In this study we will investigate the impact of genomic variability on inter-individual differences in SSRI dosing, plasma concentrations and pharmacodynamics during pregnancy, with a focus on genes involved in the metabolism of SSRIs, drug transporters responsible for SSRI access to the central nervous system, and genes encoding SSRI targets involved in therapeutic efficacy. 3. The Pilot Project -Assess the safety and toxicity of the drugs during pregnancy, postpartum, and in postnatal periods of development. This project will determine the maternal-fetal plasma concentrations and pharmacogenetic characteristics associated with neonatal SSRI abstinence syndrome. Maternal and fetal CYP and P-glycoprotein genotypes will be assessed for their relationship to SSRI drug concentrations and neonatal abstinence syndrome.

 描述（由申请人证明）：重度抑郁症是怀孕最大的并发症，在怀孕9个月内，NT发作的7.5％，产后最初三个月的发作中有6.5％。为了制定SSRI抗抑郁药在孕妇中的安全性和有效性。 ，MD MS（精神病学）；凯瑟琳·斯蒂卡（Catherine Stika），MD（妇产科）和Alfred George，MD（药物基因组学）。强大的编译：1。临床研究项目受试者的代谢表型，以评估CYP2D6出生后的活性2。在此研究中，与妊娠有关的治疗。 妊娠期间的SSRI剂量，血浆浓度和药效学的差异，重点是涉及SSRI代谢的基因，负责SSRI访问中枢神经系统的药物转运蛋白以及编码SSRI靶标的基因涉及的SSRI靶标Project-e发育后的药物和毒药。综合征。