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.

Public Health Relevance

Lay summary: Given the high prevalence of depression in pregnant women, the potential toxicity of antidepressant medications for the fetus, and the risk of relapse of major depression if untreated, it is critical to quantify the risks and benefits of alternative approaches used to manage depression during pregnancy. We propose to compare the effectiveness and safety of 1) specific selective serotonin reuptake inhibitors (SSRIs) and 2) continuing and discontinuing the medication for depression during pregnancy.

Agency
National Institute of Health (NIH)
Institute
Agency for Healthcare Research and Quality (AHRQ)
Type
Research Project (R01)
Project #
5R01HS018533-05
Application #
8505331
Study Section
Health Care Quality and Effectiveness Research (HQER)
Program Officer
Zhan, Chunliu
Project Start
2009-09-30
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2013
Total Cost
Indirect Cost
Name
Harvard University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
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Desai, Rishi J; Huybrechts, Krista F; Hernandez-Diaz, Sonia et al. (2015) Exposure to prescription opioid analgesics in utero and risk of neonatal abstinence syndrome: population based cohort study. BMJ 350:h2102
Bateman, Brian T; Huybrechts, Krista F; Maeda, Ayumi et al. (2015) Calcium Channel Blocker Exposure in Late Pregnancy and the Risk of Neonatal Seizures. Obstet Gynecol 126:271-8
Kim, Seoyoung C; Glynn, Robert J; Giovannucci, Edward et al. (2015) Risk of high-grade cervical dysplasia and cervical cancer in women with systemic inflammatory diseases: a population-based cohort study. Ann Rheum Dis 74:1360-7
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Bateman, Brian T; Hernandez-Diaz, Sonia; Fischer, Michael A et al. (2015) Statins and congenital malformations: cohort study. BMJ 350:h1035
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Oberg, Anna Sara; Hernandez-Diaz, Sonia; Palmsten, Kristin et al. (2014) Patterns of recurrence of postpartum hemorrhage in a large population-based cohort. Am J Obstet Gynecol 210:229.e1-8
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Palmsten, Kristin; Huybrechts, Krista F; Kowal, Mary K et al. (2014) Validity of maternal and infant outcomes within nationwide Medicaid data. Pharmacoepidemiol Drug Saf 23:646-55

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