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Risks of antidepressants during pregnancy: Selective serotonin reuptake inhibitors (SSRIs)

Donna Stewart, CM, MD, FRCPC
Simone Vigod, MD, MSc, FRCPC
Section Editors
Peter P Roy-Byrne, MD
Charles J Lockwood, MD, MHCM
Deputy Editor
David Solomon, MD


Pregnant women with psychiatric illnesses are often treated with antidepressant drugs. As an example, studies of pregnant women in Europe have found that antidepressants were used by approximately 3 percent [1-5], and in the United States by 8 percent [6-9]. The most commonly used and studied drugs are selective serotonin reuptake inhibitors (SSRIs) [1,2,6-13].

Antidepressants cross the placenta and fetal blood brain barrier. Prenatal exposure thus involves potential risks of teratogenesis, preterm birth, low birth weight, and pregnancy complications (eg, spontaneous abortion and postpartum hemorrhage), as well as postnatal effects (eg, persistent pulmonary hypertension of the newborn).

This topic reviews the potential adverse consequences that may be associated with using SSRIs during pregnancy, including teratogenicity, preterm birth, low birth weight, pregnancy complications, and perinatal mortality. The potential adverse antenatal effects of antidepressants other than SSRIs, postnatal outcomes among infants exposed in utero to antidepressants, principles of teratology, choice of treatment for depressed pregnant patients, safety of antidepressants in lactating women, and treatment of postpartum depression are discussed separately:

(See "Risks of antidepressants during pregnancy: Drugs other than selective serotonin reuptake inhibitors".)

(See "Infants with antenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs)".)


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Literature review current through: Sep 2016. | This topic last updated: Jan 3, 2016.
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  1. Petersen I, Gilbert RE, Evans SJ, et al. Pregnancy as a major determinant for discontinuation of antidepressants: an analysis of data from The Health Improvement Network. J Clin Psychiatry 2011; 72:979.
  2. Bakker MK, Kölling P, van den Berg PB, et al. Increase in use of selective serotonin reuptake inhibitors in pregnancy during the last decade, a population-based cohort study from the Netherlands. Br J Clin Pharmacol 2008; 65:600.
  3. Munk-Olsen T, Gasse C, Laursen TM. Prevalence of antidepressant use and contacts with psychiatrists and psychologists in pregnant and postpartum women. Acta Psychiatr Scand 2012; 125:318.
  4. Jimenez-Solem E, Andersen JT, Petersen M, et al. Prevalence of antidepressant use during pregnancy in Denmark, a nation-wide cohort study. PLoS One 2013; 8:e63034.
  5. Malm H, Sourander A, Gissler M, et al. Pregnancy Complications Following Prenatal Exposure to SSRIs or Maternal Psychiatric Disorders: Results From Population-Based National Register Data. Am J Psychiatry 2015; 172:1224.
  6. Mitchell AA, Gilboa SM, Werler MM, et al. Medication use during pregnancy, with particular focus on prescription drugs: 1976-2008. Am J Obstet Gynecol 2011; 205:51.e1.
  7. Huybrechts KF, Palmsten K, Mogun H, et al. National trends in antidepressant medication treatment among publicly insured pregnant women. Gen Hosp Psychiatry 2013; 35:265.
  8. Andrade SE, Raebel MA, Brown J, et al. Use of antidepressant medications during pregnancy: a multisite study. Am J Obstet Gynecol 2008; 198:194.e1.
  9. Hayes RM, Wu P, Shelton RC, et al. Maternal antidepressant use and adverse outcomes: a cohort study of 228,876 pregnancies. Am J Obstet Gynecol 2012; 207:49.e1.
  10. Byatt N, Deligiannidis KM, Freeman MP. Antidepressant use in pregnancy: a critical review focused on risks and controversies. Acta Psychiatr Scand 2013; 127:94.
  11. Huybrechts KF, Palmsten K, Avorn J, et al. Antidepressant use in pregnancy and the risk of cardiac defects. N Engl J Med 2014; 370:2397.
  12. Alwan S, Reefhuis J, Rasmussen SA, et al. Patterns of antidepressant medication use among pregnant women in a United States population. J Clin Pharmacol 2011; 51:264.
  13. Nordeng H, van Gelder MM, Spigset O, et al. Pregnancy outcome after exposure to antidepressants and the role of maternal depression: results from the Norwegian Mother and Child Cohort Study. J Clin Psychopharmacol 2012; 32:186.
  14. Stewart DE. Clinical practice. Depression during pregnancy. N Engl J Med 2011; 365:1605.
  15. Yonkers KA, Wisner KL, Stewart DE, et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Gen Hosp Psychiatry 2009; 31:403.
  16. Bar-Oz B, Einarson T, Einarson A, et al. Paroxetine and congenital malformations: meta-Analysis and consideration of potential confounding factors. Clin Ther 2007; 29:918.
  17. Koren G. The effect of ascertainment bias in evaluating gestational antidepressant exposure. J Popul Ther Clin Pharmacol 2011; 18:e174.
  18. Kulin NA, Pastuszak A, Sage SR, et al. Pregnancy outcome following maternal use of the new selective serotonin reuptake inhibitors: a prospective controlled multicenter study. JAMA 1998; 279:609.
  19. Greene MF. Teratogenicity of SSRIs--serious concern or much ado about little? N Engl J Med 2007; 356:2732.
  20. Louik C, Lin AE, Werler MM, et al. First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. N Engl J Med 2007; 356:2675.
  21. Ban L, Gibson JE, West J, et al. Maternal depression, antidepressant prescriptions, and congenital anomaly risk in offspring: a population-based cohort study. BJOG 2014; 121:1471.
  22. Simon GE, Cunningham ML, Davis RL. Outcomes of prenatal antidepressant exposure. Am J Psychiatry 2002; 159:2055.
  23. Reis M, Källén B. Combined use of selective serotonin reuptake inhibitors and sedatives/hypnotics during pregnancy: risk of relatively severe congenital malformations or cardiac defects. A register study. BMJ Open 2013; 3.
  24. Vasilakis-Scaramozza C, Aschengrau A, Cabral H, Jick SS. Antidepressant use during early pregnancy and the risk of congenital anomalies. Pharmacotherapy 2013; 33:693.
  25. Furu K, Kieler H, Haglund B, et al. Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: population based cohort study and sibling design. BMJ 2015; 350:h1798.
  26. Alwan S, Reefhuis J, Rasmussen SA, et al. Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. N Engl J Med 2007; 356:2684.
  27. Grigoriadis S, VonderPorten EH, Mamisashvili L, et al. Antidepressant exposure during pregnancy and congenital malformations: is there an association? A systematic review and meta-analysis of the best evidence. J Clin Psychiatry 2013; 74:e293.
  28. National Institute for Health and Care Excellence (NICE). Antenatal and postnatal mental health: clinical management and service guidance. NICE clinical guideline 192. December 2014. http://www.nice.org.uk/guidance/cg192 (Accessed on October 18, 2015).
  29. Reis M, Källén B. Delivery outcome after maternal use of antidepressant drugs in pregnancy: an update using Swedish data. Psychol Med 2010; 40:1723.
  30. Huang H, Coleman S, Bridge JA, et al. A meta-analysis of the relationship between antidepressant use in pregnancy and the risk of preterm birth and low birth weight. Gen Hosp Psychiatry 2014; 36:13.
  31. Ross LE, Grigoriadis S, Mamisashvili L, et al. Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis. JAMA Psychiatry 2013; 70:436.
  32. Lindqvist PG, Nasiell J, Gustafsson LL, Nordstrom L. Selective serotonin reuptake inhibitor use during pregnancy increases the risk of postpartum hemorrhage and anemia: a hospital-based cohort study. J Thromb Haemost 2014; 12:1986.
  33. Huybrechts KF, Sanghani RS, Avorn J, Urato AC. Preterm birth and antidepressant medication use during pregnancy: a systematic review and meta-analysis. PLoS One 2014; 9:e92778.
  34. Kjaersgaard MI, Parner ET, Vestergaard M, et al. Prenatal antidepressant exposure and risk of spontaneous abortion - a population-based study. PLoS One 2013; 8:e72095.
  35. Andersen JT, Andersen NL, Horwitz H, et al. Exposure to selective serotonin reuptake inhibitors in early pregnancy and the risk of miscarriage. Obstet Gynecol 2014; 124:655.
  36. Palmsten K, Huybrechts KF, Michels KB, et al. Antidepressant use and risk for preeclampsia. Epidemiology 2013; 24:682.
  37. Palmsten K, Setoguchi S, Margulis AV, et al. Elevated risk of preeclampsia in pregnant women with depression: depression or antidepressants? Am J Epidemiol 2012; 175:988.
  38. Palmsten K, Hernández-Díaz S, Huybrechts KF, et al. Use of antidepressants near delivery and risk of postpartum hemorrhage: cohort study of low income women in the United States. BMJ 2013; 347:f4877.
  39. Grzeskowiak LE, McBain R, Dekker GA, Clifton VL. Antidepressant use in late gestation and risk of postpartum haemorrhage: a retrospective cohort study. BJOG 2015.
  40. Jimenez-Solem E, Andersen JT, Petersen M, et al. SSRI use during pregnancy and risk of stillbirth and neonatal mortality. Am J Psychiatry 2013; 170:299.
  41. Stephansson O, Kieler H, Haglund B, et al. Selective serotonin reuptake inhibitors during pregnancy and risk of stillbirth and infant mortality. JAMA 2013; 309:48.
  42. Ericson A, Källén B, Wiholm B. Delivery outcome after the use of antidepressants in early pregnancy. Eur J Clin Pharmacol 1999; 55:503.
  43. Malm H, Klaukka T, Neuvonen PJ. Risks associated with selective serotonin reuptake inhibitors in pregnancy. Obstet Gynecol 2005; 106:1289.
  44. Sivojelezova A, Shuhaiber S, Sarkissian L, et al. Citalopram use in pregnancy: prospective comparative evaluation of pregnancy and fetal outcome. Am J Obstet Gynecol 2005; 193:2004.
  45. Reefhuis J, Devine O, Friedman JM, et al. Specific SSRIs and birth defects: Bayesian analysis to interpret new data in the context of previous reports. BMJ 2015; 351:h3190.
  46. Malm H, Artama M, Gissler M, Ritvanen A. Selective serotonin reuptake inhibitors and risk for major congenital anomalies. Obstet Gynecol 2011; 118:111.
  47. Pedersen LH, Henriksen TB, Vestergaard M, et al. Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: population based cohort study. BMJ 2009; 339:b3569.
  48. Briggs GG, Freeman RK. Citalopram. In: Drugs in Pregnancy and Lactation, Tenth Edition, Wolters Kluwer, Philadelphia 2015. p.281.
  49. De Vera MA, Bérard A. Antidepressant use during pregnancy and the risk of pregnancy-induced hypertension. Br J Clin Pharmacol 2012; 74:362.
  50. Addis A, Koren G. Safety of fluoxetine during the first trimester of pregnancy: a meta-analytical review of epidemiological studies. Psychol Med 2000; 30:89.
  51. Briggs GG, Freeman RK. Fluoxetine. In: Drugs in Pregnancy and Lactation, Tenth Edition, Wolters Kluwer, Philadelphia 2015. p.563.
  52. Myles N, Newall H, Ward H, Large M. Systematic meta-analysis of individual selective serotonin reuptake inhibitor medications and congenital malformations. Aust N Z J Psychiatry 2013; 47:1002.
  53. Briggs GG, Freeman RK. Paroxetine. In: Drugs in Pregnancy and Lactation, Tenth Edition, Wolters Kluwer, Philadelphia 2015. p.1060.
  54. Cole JA, Ephross SA, Cosmatos IS, Walker AM. Paroxetine in the first trimester and the prevalence of congenital malformations. Pharmacoepidemiol Drug Saf 2007; 16:1075.
  55. Diav-Citrin O, Shechtman S, Weinbaum D, et al. Paroxetine and fluoxetine in pregnancy: a prospective, multicentre, controlled, observational study. Br J Clin Pharmacol 2008; 66:695.
  56. Einarson A, Pistelli A, DeSantis M, et al. Evaluation of the risk of congenital cardiovascular defects associated with use of paroxetine during pregnancy. Am J Psychiatry 2008; 165:749.
  57. Wurst KE, Poole C, Ephross SA, Olshan AF. First trimester paroxetine use and the prevalence of congenital, specifically cardiac, defects: a meta-analysis of epidemiological studies. Birth Defects Res A Clin Mol Teratol 2010; 88:159.
  58. Briggs GG, Freeman RK. Sertraline. In: Drugs in Pregnancy and Lactation, Tenth Edition, Wolters Kluwer, Philadelphia 2015. p.1253.
  59. Oberlander TF, Warburton W, Misri S, et al. Major congenital malformations following prenatal exposure to serotonin reuptake inhibitors and benzodiazepines using population-based health data. Birth Defects Res B Dev Reprod Toxicol 2008; 83:68.