Is sertraline (Zoloft) safe to use during pregnancy?

From the Guidelines

Sertraline is generally considered one of the safer antidepressant options during pregnancy, though no medication is completely risk-free, and its use should be decided on a case-by-case basis considering the severity of maternal depression and the potential risks to the fetus 1. When considering the use of sertraline during pregnancy, it's essential to weigh the benefits of treating maternal depression against the potential risks to the fetus.

• The benefits of treating maternal depression often outweigh the potential risks of the medication, as untreated depression can lead to poor prenatal care, inadequate nutrition, increased substance use, preterm birth, low birth weight, and postpartum depression 1.
• Research suggests that sertraline has a relatively low risk of birth defects compared to some other antidepressants, although some studies have noted a small increased risk of certain heart defects 1.
• There is also a small risk of neonatal adaptation syndrome (temporary withdrawal symptoms in newborns) and a possible slight increase in the risk of persistent pulmonary hypertension of the newborn 1.
• A recent review of maternal antidepressant use during pregnancy found that intrauterine antidepressant exposure does not substantially increase the risk for neurodevelopmental problems such as autism spectrum disorder and attention-deficit/hyperactivity disorder 1.
• The American Psychiatric Association and the American College of Obstetricians and Gynecologists recommend that women and their doctors work together to consider the severity of current symptoms, previous mental health history, and patient treatment preferences when making decisions about antidepressant use during pregnancy 1.
• Ultimately, the decision to use sertraline during pregnancy should be made in consultation with a healthcare provider, taking into account the individual woman's circumstances and the potential risks and benefits of treatment 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). The no effect dose for rat pup mortality was 10 mg/kg (0. 5 times the MRHD on a mg/m2 basis). The decrease in pup survival was shown to be due to in utero exposure to sertraline. 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 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. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome (see WARNINGS: Serotonin Syndrome). Infants exposed to SSRIs in pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1 to 2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality Several recent epidemiologic studies suggest a positive statistical association between SSRI use (including sertraline) in pregnancy and PPHN. Other studies do not show a significant statistical association Physicians should also note the results of a prospective longitudinal study of 201 pregnant women with a history of major depression, who were either on antidepressants or had received antidepressants less than 12 weeks prior to their last menstrual period, and were in remission Women who discontinued antidepressant medication during pregnancy showed a significant increase in relapse of their major depression compared to those women who remained on antidepressant medication throughout pregnancy When treating a pregnant woman with sertraline, the physician should carefully consider both the potential risks of taking an SSRI, along with the established benefits of treating depression with an antidepressant. The decision can only be made on a case by case basis

Sertraline use in pregnancy should be carefully considered, as there are potential risks to the fetus.

• The drug label indicates that sertraline should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus 2.
• There are no adequate and well-controlled studies in pregnant women, but reproduction studies in rats and rabbits have shown some adverse effects on fetuses and pups at doses similar to or higher than the maximum recommended human dose.
• Neonates exposed to sertraline in the third trimester may be at risk for complications, including respiratory distress and persistent pulmonary hypertension of the newborn (PPHN).
• However, a prospective longitudinal study suggests that discontinuing antidepressant medication during pregnancy may increase the risk of relapse of major depression in women 2. Therefore, the decision to use sertraline during pregnancy should be made on a case-by-case basis, weighing the potential benefits and risks.

From the Research

Sertraline Use in Pregnancy

• Sertraline, also known as Zoloft, is a selective serotonin reuptake inhibitor (SSRI) commonly prescribed to treat depression and anxiety in pregnant women 3, 4.
• The literature suggests that sertraline has a relatively safe profile compared to other SSRIs, with paroxetine and fluoxetine having stronger associations with negative outcomes such as significant malformations, persistent pulmonary hypertension (PPHN), and poor neonatal adaptation syndrome (PNAS) 3.
• Studies have shown that sertraline can be continued during breastfeeding, as the concentration found in breast milk is very low and has not been linked to infant complications 3, 4.

Risks and Benefits

• The use of sertraline during pregnancy has been associated with some risks, including sex-specific effects on behavior in adult offspring, such as impacted stress response, anxiety-like behavior, and cognitive performance in female offspring, and impulsivity in females and exploratory behavior in males 5.
• However, the benefits of sertraline treatment during pregnancy may outweigh the risks, particularly for women with moderate to severe depression or anxiety 4, 6.
• It is essential to monitor sertraline plasma concentrations during pregnancy, as they may decrease, particularly in women with poor or intermediate CYP2C19 activity, which may lead to subtherapeutic concentrations 6, 7.

Pharmacokinetics and Transfer to Infants

• Sertraline concentrations in pregnant women are relatively steady, but the 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 7.
• The interindividual variation in maternal sertraline concentrations during pregnancy is significant, highlighting the need for therapeutic drug monitoring to ensure safe treatment 7.