What are the effects of paroxetine (selective serotonin reuptake inhibitor, SSRI) on pregnancy?

From the Guidelines

Paroxetine should be used with caution during pregnancy, and alternative treatments such as sertraline or citalopram may be considered due to potential risks of birth defects and pregnancy complications. According to the most recent and highest quality study, 1, the research suggests that intrauterine antidepressant exposure does not substantially increase the risk for neurodevelopmental problems, but other risk factors such as having a mother with an indication for antidepressant treatment may contribute to the increased occurrence of these problems.

Key Considerations

• The American Psychiatric Association and the American College of Obstetricians and Gynecologists recommend that women and their doctors consider severity of current symptoms, previous mental health history, and patient treatment preferences when making decisions about antidepressant use during pregnancy 1.
• A population-based cohort study of nearly 1 million pregnant women suggested that there is no link between first-trimester antidepressant use and cardiac malformations, but a meta-analysis of five trials supported the link between late pregnancy exposure to SSRIs and persistent pulmonary hypertension of the newborn (PPHN) 1.
• Paroxetine is the only SSRI for which the ratio of infant to maternal plasma concentrations is low and uniformly <0.10, making it a safer option for breastfeeding mothers 1.

Recommendations

• For women with mild depression, monitoring and encouragement to exercise and seek social support may be sufficient, while women with moderate-to-severe depression may require evidence-based treatment such as cognitive therapy or antidepressants 1.
• If paroxetine is used during pregnancy, the lowest effective dose should be used with careful monitoring, and abrupt discontinuation should be avoided to minimize withdrawal symptoms and potential relapse of depression or anxiety.
• Alternative treatments such as sertraline or citalopram may be considered due to potential risks of birth defects and pregnancy complications associated with paroxetine.

From the FDA Drug Label

Epidemiological studies have shown that infants exposed to paroxetine in the first trimester of pregnancy have an increased risk of congenital malformations, particularly cardiovascular malformations The findings from these studies are summarized below: A study based on Swedish national registry data demonstrated that infants exposed to paroxetine during pregnancy (n = 815) had an increased risk of cardiovascular malformations (2% risk in paroxetine-exposed infants) compared to the entire registry population (1% risk), for an odds ratio (OR) of 1.8 (95% confidence interval 1.1 to 2. 8). If a patient becomes pregnant while taking paroxetine, she should be advised of the potential harm to the fetus. Unless the benefits of paroxetine to the mother justify continuing treatment, consideration should be given to either discontinuing paroxetine therapy or switching to another antidepressant

Paroxetine use in pregnancy is associated with an increased risk of congenital malformations, particularly cardiovascular malformations. The available data suggest that infants exposed to paroxetine in the first trimester of pregnancy have a higher risk of cardiovascular malformations, with an odds ratio of 1.8 compared to the general population.

• Key points:
  • Increased risk of congenital malformations, particularly cardiovascular malformations
  • Infants exposed to paroxetine in the first trimester of pregnancy are at higher risk
  • Benefits of paroxetine to the mother should be weighed against potential harm to the fetus
• Recommendation: Consider discontinuing paroxetine therapy or switching to another antidepressant if a patient becomes pregnant while taking paroxetine, unless the benefits to the mother justify continuing treatment 2.

From the Research

Paroxetine Use During Pregnancy

• Paroxetine is a selective serotonin reuptake inhibitor (SSRI) that has been associated with an increased risk of congenital malformations, particularly cardiac malformations, when used during pregnancy 3, 4, 5, 6.
• Studies have shown that paroxetine use during the first trimester of pregnancy is associated with a higher risk of major cardiac malformations, including bulbus cordis anomalies, anomalies of cardiac septal closure, atrial septal defects, and right ventricular outflow track defect 6.
• The risk of major congenital malformations associated with paroxetine use during pregnancy has been estimated to be around 1.23-1.38 times higher than non-exposure to paroxetine 6.
• Some studies have suggested that paroxetine may cause adverse outcomes in the neonate when used during pregnancy, including neonatal withdrawal symptoms such as respiratory distress, irritability, lethargy, and tremors 5.
• The use of paroxetine during pregnancy has been discouraged by some guidelines due to the potential risks associated with its use 3, 4.

Comparison with Other SSRIs

• Other SSRIs, such as sertraline and fluoxetine, have also been associated with an increased risk of congenital malformations, although the evidence is not as strong as it is for paroxetine 3, 4.
• Citalopram and sertraline are considered to be safer options for use during pregnancy, although the evidence is still limited 3.
• Fluvoxamine and escitalopram have limited data available, but current evidence does not indicate a specific risk associated with their use during pregnancy 3.

Clinical Recommendations

• Paroxetine should be used with caution during pregnancy, and alternative treatments should be considered whenever possible 3, 4.
• Women who are pregnant or trying to become pregnant should be closely monitored for any potential adverse effects associated with paroxetine use 5.
• The benefits and risks of paroxetine use during pregnancy should be carefully weighed, and patients should be informed of the potential risks associated with its use 4.