Published: May 2008

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SSRI Use in Pregnancy - Collaborative Decision-Making is Key

Information on this subject has been updated. Read the most recent information.

Prescriber Update 29(1): 7-8
May 2008

Medsafe Editorial Team

Recent studies suggest that SSRI antidepressant use in pregnancy may increase the risk of congenital abnormalities.  There is also evidence to suggest that use of these medicines in later stages of pregnancy can lead to neonatal complications indicative of a withdrawal syndrome, and to persistent pulmonary hypertension of the newborn.  As untreated depression can adversely affect maternal and foetal well-being, decisions about the treatment of depression in pregnant women may be challenging for healthcare professionals and patients.  Prescribers are encouraged to discuss the potential benefits and risks of antidepressant treatment with patients who are pregnant or are contemplating pregnancy.

Prenatal exposure to SSRIs associated with increased risk of adverse pregnancy outcomes

Selective Serotonin Reuptake Inhibitors (SSRIs) are licensed in New Zealand for the treatment of depression, anxiety, and obsessive-compulsive disorders.  Recent evidence suggests that the use of these medicines in pregnancy may be uncommonly associated with an increased risk of adverse effects in the newborn.^1-6

Possible increased risk of congenital malformations with first trimester exposure

Recent studies have raised concerns about a possible association between maternal use of SSRIs and an increased risk of congenital malformations.  These include cleft palate, hypospadias, and cardiovascular abnormalities such as septal defects.^1-3  Data suggest that the risk of birth defects for women with first trimester paroxetine exposure may increase from 3% to around 4% for all congenital malformations, and from 1% to around 2% for congenital cardiac abnormalities. In studies of paroxetine, the majority of abnormalities observed have been cardiovascular in nature, of which ventricular septal defects were the most common.^1-3  As yet, there is insufficient evidence to ascertain whether the risk of such congenital abnormalities is lower with other antidepressants.

Whether this observed increase in risk is attributable to SSRIs or to other confounding factors requires further analysis.  Nonetheless, this new research suggests there may be an association between SSRIs and congenital malformations; this appears to be strongest for paroxetine and club foot, neural tube defects and cardiovascular abnormalities.⁴

Risk of neonatal complications following exposure in later stages of pregnancy

Complications in the acute neonatal period have been reported in association with maternal use of paroxetine and other SSRIs in the later stages of pregnancy.^5-8  In some instances, the reported symptoms have been described as neonatal withdrawal syndrome, characterised by convulsions, irritability, excessive crying, and tremor.^5,9  Other reported clinical findings have included respiratory distress, cyanosis, apnoea, hyperreflexia, lethargy, somnolence, temperature instability, feeding difficulties, hypoglycaemia, and muscle tone abnormalities.^8,9

In a recent case-control study, maternal use of SSRIs after the first 20 weeks of pregnancy was associated with an increase in the risk of persistent pulmonary hypertension of the newborn (PPHN).⁷  Further investigation of this association is warranted; however, on the basis of this study, the absolute risk of PPHN among those who use SSRIs late in pregnancy is approximately 6 to 12 per 1000 women.  This compares to 1 to 2 cases of PPHN per 1000 women in the general population.^{7, 8}

Patient-physician discussion about risks and benefits of antidepressant treatment during pregnancy is key

Decisions surrounding minimisation of risk to the foetus while limiting morbidity from untreated maternal depression may be challenging, and should be made collaboratively with the patient.  Prescribers are therefore encouraged to discuss the potential benefits and risks of antidepressant treatment during pregnancy with female patients of child-bearing age.  If a patient receiving SSRI antidepressant therapy is pregnant or planning to become pregnant, her history should be reviewed and options considered.  The risk of foetal exposure to antidepressant medication, untreated maternal depression, and depressive relapse associated with discontinuation of maintenance treatment should be discussed.  General Practitioners may wish to seek an expert opinion from a relevant specialist.  Prescribers should be particularly vigilant when reviewing ultrasound images for pregnant women who are taking an SSRI, and if necessary arrange for maternal serum alpha-fetoprotein levels to be checked.⁹

If a decision is taken to discontinue antidepressant treatment, or switch to another antidepressant, prescribers are reminded that this should be done in accordance with the prescribing information for the medicine to avoid possible withdrawal effects.  In addition, as untreated depression can adversely affect maternal and foetal well-being, patients should be closely observed for depressive relapse if antidepressant treatment is stopped.^10,11

Competing interests (authors): none declared.

References

1. GlaxoSmithKline Clinical Trial Register. Epidemiological Study: Updated preliminary report on bupropion and other antidepressants, including paroxetine, in pregnancy and the occurrence of cardiovascular and major congenital malformation. http://ctr.gsk.co.uk/summary/paroxetine/studylist.asp 13 December 2005.
2. Wogelius P, Norgaard M, Gislum M, et al. Maternal use of selective serotonin reuptake inhibitors and risk of congenital malformations. Epidemiology 2006;17(6):701-704.
3. Kallen B. Antidepressant drugs during pregnancy and infant congenital heart defect. Reproductive Toxicology 2006;21:221-222.
4. Louik C, Lin AE, Werler MM, et al. First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. NEJM 2007;356(26):2675-2683.
5. Sanz E, de Las Cuevas C, Kiuru A, et al. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. The Lancet 2005;365:482-487.
6. Oberlander T, Warburton W, Misri S, et al. Neonatal outcomes after prenatal exposure to selective serotonin reuptake inhibitor antidepressants and maternal depression using population-based linked health data. Archives of General Psychiatry 2006;63:898-906.
7. Chambers C, Hernandez-Diaz S, Van Marter L, et al. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. New England Journal of Medicine 2006;354(6):579-587.
8. GlaxoSmithKline NZ Limited Aropax (paroxetine) data sheet 2 June 2006. www.medsafe.govt.nz/profs/Datasheet/a/Aropaxtab.htm.
9. Mitchell LE, Adzick NS, Melchionne J, et al. Spina bifida. Lancet 2004;364(9448):1885-95.
10. Nonacs R, Cohen L. Assessment and treatment of depression during pregnancy: an update. Psychiatric Clinics of North America 2003;26(3):547-562.
11. Cohen L, Altshuler L, Harlow B, et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA 2006;295(5):499-507.