What are the effects of sertraline (selective serotonin reuptake inhibitor) on the brain and fetal development during pregnancy?

From the Guidelines

Sertraline should be used during pregnancy and breastfeeding only when the benefits outweigh the risks, as determined by a healthcare provider. Sertraline is a selective serotonin reuptake inhibitor (SSRI) that works by increasing serotonin levels in the brain, which helps regulate mood. When taken during pregnancy, sertraline crosses the placenta and may affect the developing fetus. Research suggests a small increased risk of certain birth defects when taken in early pregnancy, though the absolute risk remains low 1. Some infants exposed to sertraline late in pregnancy may experience temporary withdrawal symptoms after birth, including irritability, feeding difficulties, and respiratory distress.

Key Considerations

• The decision to use sertraline during pregnancy or breastfeeding should involve careful consideration of the mother's mental health needs balanced against potential risks to the infant, with ongoing monitoring by healthcare providers 1.
• During breastfeeding, small amounts of sertraline pass into breast milk, but studies indicate these levels are generally too low to cause significant effects in most infants 1.
• However, each situation is unique, and untreated maternal depression also poses risks to infant development.

Potential Risks

• Infants with prenatal exposure to SSRIs, such as sertraline, may be at risk for manifesting clinical signs of drug toxicity or withdrawal over the first week of life 1.
• Clinicians should be aware of these potential risks and arrange for early follow-up after the initial hospital discharge.

Benefits and Risks

• The benefits of sertraline use during pregnancy and breastfeeding must be weighed against the potential risks to the infant, and healthcare providers should closely monitor the mother and infant to minimize any adverse effects 1.

From the FDA Drug Label

Pregnancy-Pregnancy Category C Reproduction studies have been performed in rats and rabbits at doses up to 80 mg/kg/day and 40 mg/kg/day, respectively 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. When pregnant rats and rabbits were given sertraline during the period of organogenesis, delayed ossification was observed in fetuses at doses of 10 mg/kg (0. 5 times the MRHD on a mg/m2 basis) in rats and 40 mg/kg (4 times the MRHD on a mg/m2 basis) in rabbits. When female rats received sertraline during the last third of gestation and throughout lactation, there was an increase in the number of stillborn pups and in the number of pups dying during the first 4 days after birth. Pup body weights were also decreased during the first four days after birth These effects occurred at a dose of 20 mg/kg (1 times the MRHD on a mg/m2 basis).

Pregnancy-Nonteratogenic Effects Neonates exposed to sertraline and other SSRIs or serotonin and norepinephrine reuptake inhibitors (SNRIs), late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying.

The use of sertraline in pregnancy may affect the development of an infant. Key points to consider are:

• Delayed ossification in fetuses at certain doses
• Increased risk of stillborn pups and pup mortality in animal studies
• Complications in neonates, including respiratory distress, seizures, and temperature instability, when exposed to sertraline in the third trimester
• Possible increased risk of persistent pulmonary hypertension of the newborn (PPHN) The decision to use sertraline during pregnancy should be made on a case-by-case basis, weighing the potential benefits against the potential risks to the fetus 2.

From the Research

Effects of Sertraline on the Brain and Infant Development

• Sertraline, a selective serotonin reuptake inhibitor (SSRI), is commonly used to treat depression during pregnancy 3.
• The drug's transfer to infants is low, with median concentrations in infants being 33% and 25% of their mothers' concentrations, measured in cord blood and infant plasma, respectively 3.
• However, the interindividual variation in maternal concentrations during pregnancy is significant, highlighting the need for therapeutic drug monitoring to ensure safety 3.

Potential Risks to Infant Development

• Some studies suggest that SSRI use during pregnancy may be associated with an increased risk of congenital malformations, particularly cardiac malformations 4, 5.
• A study found that sertraline exposure was associated with an increased risk of atrial/ventricular defects and craniosynostosis 6.
• Another study found that SSRI use during pregnancy was associated with an increased risk of major congenital malformations, congenital heart defects, preterm birth, and neonatal adaptation symptoms 7.

Considerations for Treatment

• The use of SSRIs during pregnancy should be carefully weighed against the potential risks and benefits, particularly for women with mild depression 4.
• Alternative treatments, such as psychotherapy, may be considered as a first-line treatment during pregnancy 7.
• Therapeutic drug monitoring may be necessary to ensure the safe use of sertraline during pregnancy, particularly in women with poor metabolizing capabilities 3.