Skip to main content

Advertisement

Log in

Antidepressant use in pregnancy: are we closer to consensus?

  • Review Article
  • Published:
Archives of Women's Mental Health Aims and scope Submit manuscript

Abstract

We specify and summarize significant data from recent large studies in a tool with which to aim at consensus on the question of whether and how serotonin-reuptake antidepressants should be used in pregnancy, on the basis that concern for the mental health of the mother should not vie for primacy with concern for the short-, medium-, and long-term health of the child, but must be best served together. Side effects are small but significant over the majority of 11 categories, perinatal and into adolescence. In clinical practice, alternatives for serotonin-reuptake medication in pregnancy should be more actively pursued.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Notes

  1. An essay concerning human understanding. London, 1689

  2. An enquiry concerning human understanding. Clarendon Press, Oxford, UK, 2000, edited by Tom L. Beauchamp (EHU).

References

  • Akioyamen LE, Minhas H, Holloway AC, Taylor VH, Akioyamen NO, Sherifali D (2016) Effects of depression pharmacotherapy in fertility treatment on conception, birth, and neonatal health: a systematic review. J Psychosom Res 84:69–80

    Article  Google Scholar 

  • Almeida ND, Basso O, Abrahamowicz M, Gagnon R, Tamblyn R (2016) Risk of miscarriage in women receiving antidepressants in early pregnancy, correcting for induced abortions. Epidemiology 27(4):538–546

    Article  Google Scholar 

  • Ayd FJ Jr (1968) Phenothiazine therapy during pregnancy: effects on the newborn. Int Drug Ther Newsl 3:39

    Google Scholar 

  • Bérard A, Sheehy O, Zhao J-P, Vinet É, Bernatsky S, Abrahamowicz M (2017a) SSRI and SNRI use during pregnancy and the risk of persistent pulmonary hypertension of the newborn. Br J Clin Pharmacol 83:1126–1133. https://doi.org/10.1111/bcp.13194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bérard A, Zhao JP, Sheehy O (2017b) Antidepressant use during pregnancy and the risk of major congenital malformations in a cohort of depressed pregnant women: an updated analysis of the Quebec pregnancy cohort. BMJ Open 7:1

    Article  Google Scholar 

  • Boukhris T, Sheehy O, Mottron L, Bérard A (2016) Antidepressant use during pregnancy and the risk of autism spectrum disorder in children. JAMA Pediatr 170(2):117–124

    Article  Google Scholar 

  • Brown AS, Gyllenberg D, Malm H, McKeague IW, Hinkka-Yli-Salomäki S, Artama M, Gissler M, Cheslack-Postava K, Weissman MM, Gingrich JA, Sourander A (2016) Association of selective serotonin reuptake inhibitor exposure during pregnancy with speech, scholastic, and motor disorders in offspring. JAMA Psychiatry 73(11):1163–1170

    Article  Google Scholar 

  • Campagne DM (2007) Fact: antidepressants and anxiolytics are not safe during pregnancy. Eur J Obstet Gynecol Reprod Biol 135(2):145–148

    Article  CAS  Google Scholar 

  • Casey KF, Levesque ML, Szyf M, Ismaylova E, Verner M-P, Suderman M, Vitaro F, Brendgen M, Dionne G, Boivin M, Tremblay RE, Booij L (2016) Birth weight discordance, DNA methylation, and cortical morphology of adolescent monozygotic twins. Hum Brain Mapp 38:2037–2050. https://doi.org/10.1002/hbm.23503

    Article  PubMed  Google Scholar 

  • Castro VM, Kong SW, Clements CC, Brady R, Kaimal AJ, Doyle AE, Robinson EB, Churchill SE, Kohane IS, Perlis RH (2016) Absence of evidence for increase in risk for autism or attention-deficit hyperactivity disorder following antidepressant exposure during pregnancy: a replication study. Transl Psychiatry 6:e708

    Article  CAS  Google Scholar 

  • Chisolm MS, Payne JL (2016) Management of psychotropic drugs during pregnancy. BMJ 532:h5918

    Article  Google Scholar 

  • Clark DM (2011) Implementing NICE guidelines for the psychological treatment of depression and anxiety disorders: the IAPT experience. Int Rev Psychiatry 23:375–384

    Article  Google Scholar 

  • Cuijpers P, Sijbrandij M, Koole SL, Andersson G, Beekman AT, Reynolds CF (2013) The efficacy of psychotherapy and pharmacotherapy in treating depressive and anxiety disorders: a meta-analysis of direct comparisons. World Psychiatry 12:137–148

    Article  Google Scholar 

  • Duke JW, Gladstone IM, Sheel AW, Lovering AT (2017) Premature birth affects the degree of airway dysanapsis and mechanical ventilatory constraints. Experimental Physiology. https://doi.org/10.1113/EP086588

  • Durham E, Jen S, Wang L, Nasworthy J, Elsalanty M, Weinberg S, Yu J, Cray J (2015) Effects of citalopram on sutural and calvarial cell processes. PLoS One 10(10):e0139719

    Article  Google Scholar 

  • Dwyer T, Magnus T, Olsen J (2017) In the aftermath of the national children’s study. JAMA Pediatrics

  • Eke AC, Saccone G, Berghella V (2016) Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and risk of preterm birth: a systematic review and meta-analysis. BJOG 123(12):1900–1907

    Article  CAS  Google Scholar 

  • Etwel F, Koren G (2016) Bias against the null hypothesis in retrospective registries of gestational drug exposure. J Obstet Gynaecol Can 38(12):1120–1123

    Article  Google Scholar 

  • Food and Drug Administration (2017). Food and Drug Administration advise on drug safety. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm283375.htm. Accessed 4 Jan 2017

  • Forsberg L, Navér L, Gustafsson LL, Wide K (2014) Neonatal adaptation in infants prenatally exposed to antidepressants—clinical monitoring using neonatal abstinence score. PLoS One 9(11):e111327

    Article  Google Scholar 

  • Gentile S (2015) Prenatal antidepressant exposure and the risk of autism spectrum disorders in children. Are we looking at the fall of Gods? J Affect Disord 182:132–137

    Article  CAS  Google Scholar 

  • Gentile S, Fusco ML (2016) Placental and fetal effects of antenatal exposure to antidepressants or untreated maternal depression. J Matern Fetal Neonatal Med 21:1–11

    Article  Google Scholar 

  • Gjerde LC, Eilertsen EM, Reichborn-Kjennerud T, McAdams TA, Zachrisson HD, Zambrana IM, Røysamb E, Kendler KS, Ystrom E (2017) Maternal perinatal and concurrent depressive symptoms and child behavior problems: a sibling comparison study. J Child Psychol Psychiatry 58:779–786. https://doi.org/10.1111/jcpp.12704

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang H, Coleman S, Bridge JA, Yonkers K, Katon W (2014) A meta-analysis of the relationship between antidepressant use in pregnancy and the risk of preterm birth and low birth weight. Gen Hosp Psychiatry 36(1):13–18

    Article  Google Scholar 

  • Huybrechts KF, Bateman BT, Palmsten K, Desai RJ, Patorno E, Gopalakrishnan C, Levin R, Mogun H, Hernandez-Diaz S (2015) Antidepressant use late in pregnancy and risk of persistent pulmonary hypertension of the newborn. JAMA 313(21):2142–2151

    Article  CAS  Google Scholar 

  • Iliodromiti S, Mackay DF, Smith GCS, Pell JP, Sattar N, Lawlor DA, Nelson SM (2017) Customised and noncustomised birth weight centiles and prediction of stillbirth and infant mortality and morbidity: a cohort study of 979,912 term singleton pregnancies in Scotland. PLOS Med. https://doi.org/10.1371/journal.pmed.1002228

  • Jha SC, Meltzer-Brody S, Steiner RJ, Cornea E, Woolson S, Ahn M, Verde AR, Hamer RM, Zhu H, Styner M, Gilmore JH, Knickmeyer RC (2016) Antenatal depression, treatment with selective serotonin reuptake inhibitors, and neonatal brain structure: a propensity-matched cohort study. Psychiatry Res 253:43–53

    Article  Google Scholar 

  • Jordan S, Morris JK, Davies GI, Tucker D, Thayer DS, Luteijn JM, Morgan M, Garne E, Hansen AV, Klungsøyr K, Engeland A, Boyle B, Dolk H (2016) Selective serotonin reuptake inhibitor (SSRI) antidepressants in pregnancy and congenital anomalies: analysis of linked databases in Wales, Norway and Funen, Denmark. PLoS One 11(12):e0165122

    Article  Google Scholar 

  • Júlíusson PB, Roelants M, Eide GE, Moster D, Juul A, Hauspie R, Waaler PE, Bjerknes R (2009) Growth charts for Norwegian children. Tidsskr Nor Legefore 129:281–286

    Article  Google Scholar 

  • Kaltenbach K, Jones HE (2016) Neonatal abstinence syndrome: presentation and treatment considerations. J Addict Med 10:217–223

    Article  Google Scholar 

  • Khan A, Faucett J, Lichtenberg P, Kirsch I, Brown WA (2012) A systematic review of comparative efficacy of treatments and controls for depression. PLoS One 7(7):e41778. https://doi.org/10.1371/journal.pone.0041778 Epub 2012 Jul 30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kieler H, Artama M, Engeland A, Ericsson O, Furu K, Gissler M, Nielsen RB, Nørgaard M, Stephansson O, Valdimarsdottir U, Zoega H, Haglund B (2012) Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries. BMJ 344:d8012

    Article  Google Scholar 

  • Kieviet N, Dolman KM, Honig A (2013) The use of psychotropic medication during pregnancy: how about the newborn? Neuropsychiatr Dis Treat 9:1257–1266

    Article  Google Scholar 

  • Kieviet N, van Ravenhorst M, Dolman KM, van de Ven PM, Heres M, Wennink H, Honig A (2015) Adapted Finnegan scoring list for observation of anti-depressant exposed infants. J Matern Fetal Neonatal Med 28(17):2010–2014

    Article  Google Scholar 

  • Klinger G, Frankenthal D, Merlob P, Diamond G, Sirota L, Levinson-Castiel R, Linder N, Stahl B, Inbar D (2011) Long-term outcome following selective serotonin reuptake inhibitor induced neonatal abstinence syndrome. J Perinatol 31:615–620

    Article  CAS  Google Scholar 

  • Ko JY, Farr SL, Dietz PM, Robbins CL (2012) Depression and treatment among U.S. pregnant and nonpregnant women of reproductive age, 2005–2009. J Womens Health (Larchmt) 21(8):830–836. https://doi.org/10.1089/jwh.2011.3466

    Article  Google Scholar 

  • Koren G, Nordeng H (2012) Antidepressant use during pregnancy: the benefit-risk ratio. Am J Obstet Gynecol 207(3):157–163

    Article  Google Scholar 

  • Levinson-Castiel R, Merlob P, Linder N, Sirota L, Klinger G (2006) Neonatal abstinence syndrome after in utero exposure to selective serotonin reuptake inhibitors in term infants. Arch Pediatr Adolesc Med 160:173–176

    Article  Google Scholar 

  • Malm H, Sourander A, Gissler M, Gyllenberg D, Hinkka-Yli-Salomäki S, McKeague IW, Artama M, Brown AS (2015) Pregnancy complications following prenatal exposure to SSRIs or maternal psychiatric disorders: results from population-based national register data. Am J Psychiatry 172(12):1224–1232

    Article  Google Scholar 

  • Malm H, Brown AS, Gissler M, Gyllenberg D, Hinkka-Yli-Salomäki S, McKeague IW, Weissman M, Wickramaratne P, Artama M, Gingrich JA, Sourander A (2016) Gestational exposure to selective serotonin reuptake inhibitors and offspring psychiatric disorders: a national register-based study. J Am Acad Child Adolesc Psychiatry 55(5):359–366

    Article  Google Scholar 

  • Manber R, Schnyer RN, Lyell D, Chambers AS, Caughey AB, Druzin M, Carlyle E, Celio C, Gress JL, Huang MI, Kalista T, Martin-Okada R, Allen JJB (2010) Acupuncture for depression during pregnancy: a randomized controlled trial. Obstet Gynecol 115(3):511–520. https://doi.org/10.1097/AOG.0b013e3181cc0816

    Article  PubMed  Google Scholar 

  • Mao Y, Pedersen LH, Christensen J, Vestergaard M, Zhou W, Olsen J, Sun Y (2016) Prenatal exposure to antidepressants and risk of epilepsy in childhood. Pharmacoepidemiol Drug Saf 25(11):1320–1330

    Article  CAS  Google Scholar 

  • El Marroun H, Jaddoe VW, Hudziak JJ, Roza SJ, Steegers EA, Hofman A, Verhulst FC, White TJ, Stricker BH, Tiemeier H (2012) Maternal use of selective serotonin reuptake inhibitors, fetal growth, and risk of adverse birth outcomes. Arch Gen Psychiatry 69(7):706–714

    Article  Google Scholar 

  • El Marroun H, White TJ, van der Knaap NJ, Homberg JR, Fernández G, Schoemaker NK, Jaddoe VW, Hofman A, Verhulst FC, Hudziak JJ, Stricker BH, Tiemeier H (2014) Prenatal exposure to selective serotonin reuptake inhibitors and social responsiveness symptoms of autism: population-based study of young children. Br J Psychiatry 205(2):95–102

    Article  Google Scholar 

  • McQueen K, Murphy-Oikonen J (2016) Neonatal abstinence syndrome. N Engl J Med 375:2468–2479

    Article  Google Scholar 

  • Molenaar NM, Brouwer ME, Bockting CL, Bonsel GJ, van der Veere CN, Torij HW, Hoogendijk WJ, Duvekot JJ, Burger H, Lambregtse-van den Berg MP (2016) Stop or go? Preventive cognitive therapy with guided tapering of antidepressants during pregnancy: study protocol of a pragmatic multicentre non-inferiority randomized controlled trial. BMC Psychiatry 16(72)

  • Moncrieff J, Wessely S, Hardy R (2004) Active placebos versus antidepressants for depression. Cochrane Database Syst Rev:CD003012

  • Nezvalová-Henriksen K, Spigset O, Brandlistuen RE, Ystrom E, Koren G, Nordeng H (2016) Effect of prenatal selective serotonin reuptake inhibitor (SSRI) exposure on birthweight and gestational age: a sibling-controlled cohort study. Int J Epidemiol

  • O'Connor E, Rossom RC, Henninger M, Groom HC, Burda BU (2016) Primary care screening for and treatment of depression in pregnant and postpartum women: evidence report and systematic review for the US preventive services task force. JAMA 315(4):388–406

    Article  CAS  Google Scholar 

  • O’Donnell KJ, Bugge Jensen A, Freeman L, Khalife N, O’Connor TG, Glover V (2012) Maternal prenatal anxiety and downregulation of placental 11β-HSD2. Psychoneuroendocrinology 37(6):818–826

    Article  Google Scholar 

  • Olivier JD, Åkerud H, Skalkidou A, Kaihola H, Sundström-Poromaa I (2015) The effects of antenatal depression and antidepressant treatment on placental gene expression. Front Cell Neurosci 8:465

    Article  Google Scholar 

  • Patrick SW, Dudley J, Martin PR, Harrell FE, Warren MD, Hartmann KE, Ely EW, Grijalva CG, Cooper WO (2015) Prescription opioid epidemic and infant outcomes. Pediatrics 135:842–850

    Article  Google Scholar 

  • Paz-Levy D, Shainer E, Wainstock T, Sergienko R, Landau D, Walfisch A (2017) Evidence that children born at early term (37-38 6/7 weeks) are at increased risk for diabetes and obesity-related disorders. AJOG. https://doi.org/10.1016/j.ajog.2017.07.015

  • Pedersen LH (2015) Prenatal antidepressant exposure and childhood autism spectrum disorders: cause for concern? Paediatr Drugs 17(6):443–448

    Article  Google Scholar 

  • Robinson GE (2015) Controversies about the use of antidepressants in pregnancy. J Nerv Ment Dis 203(3):159–163

    Article  Google Scholar 

  • Seth S, Lewis AJ, Saffery R, Lappas M, Galbally M (2015) Maternal prenatal mental health and placental 11β-HSD2 gene expression: initial findings from the mercy pregnancy and emotional wellbeing study. Int J Mol Sci 16(11):27482–27496

    Article  CAS  Google Scholar 

  • Sockol LE, Epperson CN, Barber JP (2011) A meta-analysis of treatments for perinatal depression. Clin Psychol Rev 31(5):839–849 Epub Mar 27, 2011

    Article  Google Scholar 

  • Uebel H, Wright IM, Burns L, Hilder L, Bajuk B, Breen C, Abdel-Latif ME, Feller JM, Falconer J, Clews S, Eastwood J, Oei JL (2015) Reasons for rehospitalization in children who had neonatal abstinence. Syndrome Pediatrics 136(4):e811–e820

    Article  Google Scholar 

  • Venkatesh KK, Riley L, Castro VM, Perlis RH, Kaimal AJ (2016) Association of antenatal depression symptoms and antidepressant treatment with preterm birth. Obstet Gynecol 127(5):926–933

    Article  CAS  Google Scholar 

  • Venkatesh KK, Castro VM, Perlis RH, Kaimal AJ (2017) Impact of antidepressant treatment during pregnancy on obstetric outcomes among women previously treated for depression: an observational cohort study. J Perinatol 37(9):1003–1009. https://doi.org/10.1038/jp.2017.92

    Article  CAS  PubMed  Google Scholar 

  • Viktorin A, Lichtenstein P, Lundholm C, Almqvist C, D’Onofrio BM, Larsson H, Landén M, Magnusson PK (2016) Selective serotonin re-uptake inhibitor use during pregnancy: association with offspring birth size and gestational age. Int J Epidemiol 45(1):170–177

    Article  Google Scholar 

  • Viuff AC, Pedersen LH, Kyng K, Staunstrup NH, Børglum A, Henriksen TB (2016, 7) Antidepressant medication during pregnancy and epigenetic changes in umbilical cord blood: a systematic review. Clin Epigenetics 8(1):94

    Article  Google Scholar 

  • Yonkers KA, Wisner KL, Stewart DE, Oberlander TF, Dell DL, Stotland N et al (2009) The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Gen Hosp Psychiatry 31(5):403–413. Also in Obstet Gynecol. 2009; 114(3): 703–13. https://doi.org/10.1097/AOG.0b013e3181ba0632

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Daniel M. Campagne.

Ethics declarations

Ethical approval

This article does not contain any studies with human participants performed by the author.

Conflict of interest

The author declares that he has no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Campagne, D.M. Antidepressant use in pregnancy: are we closer to consensus?. Arch Womens Ment Health 22, 189–197 (2019). https://doi.org/10.1007/s00737-018-0906-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00737-018-0906-2

Keywords

Navigation