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Use of antidepressants near delivery and risk of postpartum hemorrhage: cohort study of low income women in the United States

BMJ 2013; 347 doi: (Published 21 August 2013) Cite this as: BMJ 2013;347:f4877
  1. Kristin Palmsten, postdoctoral research fellow1,
  2. Sonia Hernández-Díaz, associate professor1,
  3. Krista F Huybrechts, instructor2,
  4. Paige L Williams, senior lecturer3,
  5. Karin B Michels, associate professor145,
  6. Eric D Achtyes, assistant professor6,
  7. Helen Mogun, programmer2,
  8. Soko Setoguchi, associate professor17
  1. 1Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
  2. 2Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA 02120, USA
  3. 3Department of Biostatistics, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
  4. 4Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA
  5. 5Institute for Prevention and Cancer Epidemiology, University of Freiburg Medical Center, Freiburg, Germany
  6. 6Division of Psychiatry and Behavioral Medicine, College of Human Medicine, Michigan State University, 100 Cherry Street SE, Grand Rapids, MI 49503, USA
  7. 7Duke Clinical Research Institute, Duke University School of Medicine, 2400 Pratt Street, Durham, NC 27705, USA
  1. Correspondence to: K Palmsten kkp762{at}
  • Accepted 25 July 2013


Objective To determine whether use of serotonin or non-serotonin reuptake inhibitors near to delivery is associated with postpartum hemorrhage.

Design Cohort study.

Setting 2000-07 nationwide Medicaid data (Medicaid Analytic eXtract).

Population 106 000 pregnant women aged 12-55 with a diagnosis of mood or anxiety disorder. Women were categorized into four mutually exclusive exposure groups according to pharmacy dispensing data: current (delivery date), recent (1-30 days before delivery date), past (1-5 months before delivery date), and no exposure (reference group).

Main outcome measures Risk of postpartum hemorrhage by timing of exposure and by serotonin or non-serotonin reuptake inhibitors, classes of antidepressant, and antidepressant types. Relative risks and 95% confidence intervals adjusted for delivery year, risk factors for postpartum hemorrhage, indicators of severity of mood/anxiety disorder, other indications for antidepressants, and other drugs. High dimensional propensity score (hdPS) methods were used to empirically identify and adjust for additional factors.

Results 12 710 (12%) women had current exposure to serotonin reuptake inhibitor monotherapy, and 1495 (1.4%) women had current exposure to non-serotonin reuptake inhibitor monotherapy. The risk of postpartum hemorrhage was 2.8% among women with mood/anxiety disorders but no exposure to antidepressants, 4.0% in the current users of serotonin reuptake inhibitors, 3.8% in the current users of non-serotonin reuptake inhibitors, 3.2% in the recent users of serotonin reuptake inhibitors, 3.1% in the recent users of non-serotonin reuptake inhibitors, 2.5% in the past users of serotonin reuptake inhibitors, and 3.4% in the past users of non-serotonin reuptake inhibitors. Compared with no exposure, women with current exposure to serotonin reuptake inhibitors had a 1.47-fold increased risk of postpartum hemorrhage (95% confidence interval 1.33 to 1.62) and women with current non-serotonin reuptake inhibitor exposure had a 1.39-fold increased risk (1.07 to 1.81). Results were similar with hdPS adjustment. Women with current exposure to serotonin reuptake inhibitors had an adjusted excess risk of 1.26% (0.90% to 1.62%), with a number needed to harm of 80, and for women with current exposure to non-serotonin reuptake inhibitors the excess risk was 1.03% (0.07% to 1.99%), with a number needed to harm of 97. For exposure to serotonin reuptake inhibitors the relative risk was 1.19 (1.03 to 1.38) for recent exposure and 0.93 (0.82 to 1.06) for past exposure; for non-serotonin reuptake inhibitors the figures were 1.17 (0.80 to 1.70) and 1.26 (1.00 to 1.59), respectively. Current exposure to selective serotonin reuptake inhibitor monotherapy was also associated with postpartum hemorrhage (1.42, 1.27 to 1.57), as was current serotonin norepinephrine (noradrenaline) reuptake inhibitor (1.90, 1.37 to 2.63) and tricyclic monotherapy (1.77, 0.90 to 3.47). All types of selective serotonin reuptake inhibitors available for analysis and venlafaxine, a serotonin norepinephrine reuptake inhibitor, were significantly associated with postpartum hemorrhage.

Conclusions Exposure to serotonin and non-serotonin reuptake inhibitors, including selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclics, close to the time of delivery was associated with a 1.4 to 1.9-fold increased risk for postpartum hemorrhage. While potential confounding by unmeasured factors cannot be ruled out, these findings suggest that patients treated with antidepressants during late pregnancy are more likely to experience postpartum hemorrhage.


  • Contributors: KP, SH-D, KFH, PLW, KBM, EDA, and SS were responsible for conception and design. SH-D and SS acquired the data which were analyzed and interpreted by KP, SH-D, KFH, PLW, KBM, HM, and SS. All authors critically revised the manuscript for important intellectual content. SH-D and SS obtaining funding. KP and HM provided administrative, technical, and material support. KP drafted the manuscript and is guarantor.

  • Funding: This work was supported by the Agency for Healthcare Research and Quality (AHRQ) (grant R01HS018533 to SH-D). KP was supported by training grant T32HD060454 in reproductive, perinatal, and pediatric epidemiology from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. SS was supported by a mid-career development award grant K02-HS017731 from the AHRQ. The AHRQ had no role in the study design and the collection, analysis, and interpretation of data and writing of the article and the decision to submit it for publication. Research was conducted independently of the sponsor and funders.

  • Ethical approval: This project was approved by Brigham and Women’s Hospital and Harvard School of Public Health Institutional Review Boards and a data use agreement was approved by the Centers for Medicare and Medicaid Services (CMS).

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: the Pharmacoepidemiology Program at the Harvard School of Public Health receives funding from Pfizer and Asisa; SH-D has consulted for GSK and Novartis; EA received research funding from the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Mental Health (NIMH), the National Institute on Drug Abuse (NIDA), Pfizer, Otsuka, Janssen, (all schizophrenia), Pine Rest Foundation (ECT/dementia), University of Chicago, Michigan State University, Pine Rest Foundation (depression screening tool, biomarkers of depression and suicidality), Novartis (antidepressant development), Pine Rest Foundation, AssureRx, Priority Health (pharmacogenomic testing in depression).

  • Data sharing: No additional data available.

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