What is the FDA pregnancy category of sertraline?

FDA Pregnancy Category of Sertraline

Sertraline is classified as FDA Pregnancy Category C. 1

Understanding Category C Classification

The FDA Category C designation means that either studies in animals have revealed adverse effects on the fetus and there are no controlled studies in women, or studies in women and animals are not available. 2 Drugs in this category should be given only if potential benefits justify the potential risk to the fetus. 2

Specific Evidence for Sertraline's Category C Classification

The FDA drug label explicitly states that sertraline is Pregnancy Category C based on animal reproduction studies showing adverse effects. 1

Animal Study Findings Supporting Category C:

• Reproduction studies in rats and rabbits at doses up to 80 mg/kg/day and 40 mg/kg/day (approximately 4 times the maximum recommended human dose) showed delayed ossification in fetuses at doses of 10 mg/kg in rats and 40 mg/kg in rabbits. 1
• When female rats received sertraline during the last third of gestation and throughout lactation, there was an increase in stillborn pups and pup deaths during the first 4 days after birth at doses of 20 mg/kg (1 times the maximum recommended human dose). 1
• Recent mouse studies (2020) demonstrated that sertraline at 25 and 60 mg/kg was embryotoxic, teratogenic, and fetotoxic, with cleft palate observed in 2.99% and 2.5% of fetuses at these doses, exceeding historical control ranges. 3

Human Data Limitations:

• There are no adequate and well-controlled studies in pregnant women, which is a key criterion for Category C classification. 1
• The FDA label explicitly states: "Sertraline hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus." 1

Clinical Implications of Category C Status

Neonatal Complications:

Neonates exposed to sertraline late in the third trimester have developed complications including:

• Respiratory distress, cyanosis, apnea, seizures 1
• Temperature instability, feeding difficulty, vomiting, hypoglycemia 1
• Hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability 1
• These complications can arise immediately upon delivery and may require prolonged hospitalization, respiratory support, and tube feeding. 1

Persistent Pulmonary Hypertension Risk:

• Infants exposed to SSRIs including sertraline in pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN), which occurs in 1-2 per 1000 live births and is associated with substantial neonatal morbidity and mortality. 1
• Several epidemiologic studies suggest a positive statistical association between SSRI use (including sertraline) in pregnancy and PPHN, though other studies do not show significant association. 1

Important Distinction from Category B

It is critical to note that sertraline is NOT Category B, despite some confusion in the literature. 1 Category B would indicate that animal reproduction studies have failed to demonstrate fetal risk, which is not the case for sertraline given the documented adverse effects in animal studies. 2

Clinical Decision-Making Framework

When prescribing sertraline during pregnancy, physicians must:

• Carefully weigh the potential risks of taking an SSRI against the established benefits of treating depression, as untreated maternal depression itself carries significant risks. 1
• Consider that women who discontinued antidepressants during pregnancy showed a significant increase in relapse of major depression compared to those who remained on medication. 1
• Make decisions on a case-by-case basis, as the decision can only be individualized based on severity of maternal illness and available alternatives. 1

Comparative Safety Profile

Among SSRIs, the literature suggests that sertraline and citalopram have more mixed and generally unsubstantiated associations with negative outcomes when controlled for maternal depression effects, compared to paroxetine and fluoxetine which have stronger associations with significant malformations. 4 This makes sertraline a reasonable first-line option within the SSRI class when antidepressant treatment is necessary during pregnancy, despite its Category C classification. 4