What is the safest Selective Serotonin Reuptake Inhibitor (SSRI) to use during pregnancy?

From the Guidelines

Sertraline (Zoloft) is generally considered the safest SSRI to use during pregnancy when antidepressant treatment is necessary. The typical starting dose is 25-50 mg daily, which can be gradually increased to 50-200 mg daily as needed. Sertraline has been extensively studied in pregnancy with a large safety database showing minimal risks to the developing fetus, as noted in a study published in the American Family Physician 1. It has lower placental transfer compared to other SSRIs and minimal association with congenital malformations.

While using any medication during pregnancy requires careful consideration of risks versus benefits, untreated depression itself poses significant risks to both mother and baby. Potential side effects of sertraline include nausea, insomnia, and sexual dysfunction. All SSRIs, including sertraline, carry a small risk of neonatal adaptation syndrome (temporary jitteriness, feeding difficulties) if used late in pregnancy, and there is a very slight increased risk of persistent pulmonary hypertension of the newborn, as discussed in a study published in Pediatrics 1.

Some key points to consider when prescribing sertraline during pregnancy include:

• Monitoring for signs of neonatal adaptation syndrome or serotonin syndrome in the newborn
• Regular prenatal care and communication with both an obstetrician and psychiatrist
• Counseling the mother on the risks and benefits of breastfeeding while taking an SSRI, as the transfer of antidepressants into breast milk is a consideration, with paroxetine and sertraline being the most commonly prescribed antidepressants during breastfeeding 1.
• Being aware that infants are at risk for manifesting clinical signs of drug toxicity or withdrawal over the first week of life and arranging for early follow-up after the initial hospital discharge 1.

Overall, the decision to use sertraline during pregnancy should be made on a case-by-case basis, taking into account the individual patient's needs and medical history, and with careful consideration of the potential risks and benefits.

From the FDA Drug Label

These doses correspond to approximately 4 times the maximum recommended human dose (MRHD) on a mg/m2 basis. There was no evidence of teratogenicity at any dose level. The clinical significance of these effects is unknown. There are no adequate and well-controlled studies in pregnant women. Sertraline hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus Infants exposed to SSRIs in pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN).

Safest SSRI in Pregnancy: Based on the available information, sertraline appears to be a safer option compared to paroxetine due to the lack of evidence of teratogenicity at any dose level. However, it is essential to note that:

• There are no adequate and well-controlled studies in pregnant women for sertraline.
• The clinical significance of the effects observed in animal studies is unknown.
• Sertraline should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.
• Infants exposed to sertraline in pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). It is crucial to carefully weigh the potential risks and benefits of using any SSRI during pregnancy, and paroxetine is generally not recommended due to its association with an increased risk of congenital malformations, particularly cardiovascular malformations 2 3.

From the Research

Overview of SSRI Safety in Pregnancy

• The safety of Selective Serotonin Reuptake Inhibitors (SSRIs) during pregnancy is a concern due to potential risks of birth defects and neonatal complications 4, 5.
• Untreated maternal depression also carries serious risks for both the mother and the baby, making the decision to use SSRIs during pregnancy a difficult one 4, 5.

Specific SSRIs and Associated Risks

• Sertraline use during the first trimester has been associated with an increased risk of atrial/ventricular defects and craniosynostosis 6.
• Citalopram use during the first trimester has been linked to an increased risk of vesicoureteric reflux 7.
• Paroxetine, fluoxetine, and other SSRIs have also been associated with various risks, including cardiac malformations and musculoskeletal defects 7, 6, 8.

Comparison of SSRIs

• A study found that children born to women dispensed sertraline had a higher mean birth weight than those born to women dispensed citalopram, paroxetine, or fluoxetine 7.
• However, another study found that sertraline use was associated with an increased risk of septal defects 8.

Considerations for SSRI Use in Pregnancy

• The decision to use SSRIs during pregnancy should be made after discussing the risks and benefits with a healthcare provider 4, 5.
• Women who require treatment for depression and are pregnant or planning to become pregnant should be closely monitored by their healthcare provider 4, 5.