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