Is it safe to use SSRIs during pregnancy?
Published in Health News and Evidence
Date published: About this date
Untreated depression is linked to adverse outcomes in pregnancy and management of major depressive disorder in pregnant women is important for the health and welfare of the mother and infant. Selective serotonin reuptake inhibitors (SSRIs) are the most frequently used antidepressants during pregnancy but their use in pregnancy has been controversial because of the lack of consistency in the literature about associations with adverse outcomes. Two recent studies that highlighted the importance of adjusting results for confounders indicate SSRIs are not linked with adverse events, including still births and malformations. Although further well-designed studies are needed to accurately determine the benefits and harms of individual SSRIs, all except paroxetine are currently considered relatively safe for use in pregnancy.
- Some studies1-5 have reported conflicting results for SSRIs and pregnancy-related outcomes, but many have not been adequately controlled.
- Two recent studies support the use of SSRIs during pregnancy and highlight that if results had not been adjusted for confounders, SSRI use would have been linked with adverse pregnancy outcomes.4,5
- The Australian Medicines Handbook considers SSRIs, with the exception of paroxetine, to be relatively safe for treatment of major depression during pregnancy, but highlights that the lowest effective dose should be used.6
- Australian Beyond Blue guidelines also support the use of SSRIs for depression during pregnancy.7
- Large prospective studies on the effects of individual SSRIs are needed. Studies should be adequately controlled and adjust for known confounders such as underlying depression, mental illness and smoking.
- When discussing the use of antidepressants during pregnancy, provide women with a detailed explanation of the baseline, absolute and relative risks to the foetus or infant, as well as the potential impact on the offspring of treatment versus non-treatment.8
Major depression affects up to 13% of women during pregnancy, and depression is associated with adverse outcomes for both the mother and infant, especially if untreated.9,10 These include increased rates of obstetric complications, stillbirth, suicide attempts, postnatal specialist care for the infants and low birth weight infants.8-10 Ideally, pharmacotherapy during pregnancy should be minimised, however it is important not to under treat psychiatric illness.10 Most women will relapse if treatment with an antidepressant or mood stabiliser medication is stopped on confirmation of pregnancy.10
The use of antidepressants is common during pregnancy with 1–8% of women reported to use them.4 SSRIs are the most frequently used antidepressants during pregnancy and are recommended by Australian Beyond Blue guidelines and considered relatively safe by the Australian Medicines Handbook (with the exception of paroxetine).6-8 The use of SSRIs during pregnancy has been controversial because of concerns over teratogenicity, spontaneous abortion and premature labour, low birth weight/small-for-date newborns, poor neonatal adaptation, persistent pulmonary hypertension in the neonate and neurodevelopmental difficulties in older children.10 Therapeutic Guidelines recommend that concern over teratogenicity should not deter prescription of SSRIs (with the exception of paroxetine) for treatment of major depression in pregnancy but highlight that the decision to prescribe SSRIs remains complex because of conflicting evidence and increased awareness of apparent risk.10
A recent meta-analysis of prospective studies reporting data on antenatal depression and at least 1 adverse birth outcome showed a significant risk of pre-term birth and low birth weight in women with depression regardless of whether antidepressants were used.9 This study also showed a similar incidence of pre-term births in studies which stratified the effects of antidepressants in these women with depression.9
Some studies report no effect of SSRI use on indicators such as infant mortality5, low birth weight or preterm birth4, whereas others have reported increases in certain pregnancy related adverse events including spontaneous abortion3, major malformations3 and low birth weight.2 A 2007 meta-analysis found that the levels of major congenital malformation seen in women taking the SSRIs fluoxetine, sertraline, citalopram or the serotonin–noradrenaline reuptake inhibitor venlafaxine in pregnancy is equivalent to that seen in the normal population but further evidence was needed to identify the risk associated with fluvoxamine, escitalopram and duloxetine.1 The authors advise caution in prescribing paroxetine based on positive associations with both major malformations and cardiac abnormalities in four retrospective studies.1
Issues contributing to these apparent conflicting results have been identified as: inadequate study size, lack of adjustment for confounding factors and inadequate control populations. Many studies which have linked SSRIs with adverse pregnancy outcomes have failed to account for the significant differences between individual drugs in this class, considering them as a homogenous class.3 Many studies have not accounted for known potential confounders such as the underlying depression, smoking and mental illness.2,3 Many studies have also inappropriately used healthy pregnant women2,3, rather than women with confirmed depressive disorder with no medicine use, as controls.2
A recent observational study highlighted the need to adjust for maternal level of depression either alone or together with sociodemographic and lifestyle factors.4 In this study, which adjusted data for potential confounders such as the level of maternal depression, maternal age at delivery and smoking, the use of an SSRI during the first trimester of pregnancy was not associated with an increased incidence of malformations, preterm birth or low birth weight.4
Similarly, another recent observational study of women with singleton births in Nordic countries reported that after adjustment for maternal characteristics such as maternal age, parity, birth year, country of birth and maternal smoking status, SSRI use during pregnancy was not associated with still birth, neonatal death or postneonatal death.5
Both studies reported that if results had not been adjusted for confounders, SSRI use would have been linked with adverse pregnancy outcomes.4,5 These studies also showed that women taking antidepressants during pregnancy were generally older and more likely to be smokers4,5, with a significantly higher use of other psychotropic drugs4 and were more likely to have been previously hospitalised for psychiatric illness.5
The influence of SSRIs on pregnancy is not clear at present because of conflicting results from studies. Recent studies that adjusted for confounders such as underlying depression, mental illness and smoking show no association with SSRI use in pregnancy and adverse outcomes of stillbirth, neonatal death, postneonatal death, increased incidence of malformations, preterm birth or low birth weight.4,5 In light of these recent studies current Australian Guidelines which support the use of SSRIs (with the exception of paroxetine) during pregnancy but acknowledge the complexity of the decision to prescribe, remain relevant. However, large prospective studies on the effects of individual SSRIs (which are adequately controlled and adjust for known confounders) are needed to bring further clarity.
- Bellantuono C, Migliarese G, Gentile S. Serotonin reuptake inhibitors in pregnancy and the risk of major malformations: a systematic review. Hum Psychopharmacol 2007;22:121–8. [Pubmed]
- Lattimore KA, Donn SM, Kaciroti N, et al. Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and effects on the fetus and newborn: a meta-analysis. J Perinatol 2005;25:595–604. [Pubmed]
- Nikfar S, Rahimi R, Hendoiee N, et al. Increasing the risk of spontaneous abortion and major malformations in newborns following use of serotonin reuptake inhibitors during pregnancy: A systematic review and updated meta-analysis. Daru 2012;20:75. [Pubmed]
- 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;32:186–94. [Pubmed]
- Stephansson O, Kieler H, Haglund B, et al. Selective serotonin reuptake inhibitors during pregnancy and risk of stillbirth and infant mortality. JAMA 2013;309:48–54. [Pubmed]
- Australian medicines handbook. Adelaide: Australian Medicines Handbook Pty Ltd, 2012.
- Beyond Blue. Beyond Baby Blues Perinatal depression and anxiety A guide for primary care health professionals, 2012.
- Beyond Blue. CLINICAL PRACTICE GUIDELINES Depression and related disorders –anxiety, bipolar disorder and puerperal psychosis in the perinatal period A guideline for primary care health professionals. 2011.
- Grote NK, Bridge JA, Gavin AR, et al. A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction. Arch Gen Psychiatry 2010;67:1012–24. [Pubmed]
- eTG complete [Internet]. General information on drug use in pregnancy: psychotropic drugs. Melbourne: Therapeutic Guidelines Ltd, 2008.