Is Zoloft (sertraline) safe to use during pregnancy?

From the Guidelines

Zoloft (sertraline) can be used during pregnancy, but the decision should be made after weighing the benefits of treating maternal depression against potential risks to the developing baby, and it is recommended to continue treatment at the lowest effective dose 1. The use of Zoloft during pregnancy involves considering the potential risks and benefits, including the risk of neonatal adaptation syndrome, which can manifest with symptoms such as irritability, feeding difficulties, and respiratory distress 1. Some studies suggest a small increased risk of birth defects, particularly heart defects, though the absolute risk remains very low. It is essential to consult a healthcare provider to discuss the specific situation, considering factors like the severity of depression, previous response to treatment, and personal medical history. 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. Key points to consider include:

• The potential risks of Zoloft use during pregnancy, including neonatal adaptation syndrome and birth defects
• The benefits of treating maternal depression, including improved prenatal care and reduced risk of complications during delivery
• The importance of consulting a healthcare provider to discuss the specific situation and determine the best course of treatment
• The recommendation to continue treatment at the lowest effective dose to minimize potential risks to the developing baby. In terms of neurodevelopmental outcomes, research suggests that intrauterine antidepressant exposure does not substantially increase the risk for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) 1. However, it is crucial to provide services to women with depressive and anxiety disorders and their children to reduce the risk of offspring neurodevelopmental problems. A stepped approach to treatment of depression during pregnancy is recommended, which includes monitoring and encouraging exercise and social support for women with mild depression, and offering evidence-based treatment for women with moderate-to-severe depression 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

Zoloft (sertraline) use during pregnancy should be carefully considered, as there are potential risks to the fetus.

• The drug label indicates that there is no evidence of teratogenicity at any dose level in rats and rabbits.
• However, delayed ossification was observed in fetuses at certain doses, and increased stillborn pups and pup mortality were seen in rat studies.
• Neonates exposed to sertraline late in the third trimester may develop complications, including respiratory distress and 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.
• Physicians should carefully consider the potential risks and benefits of treatment with sertraline during pregnancy 2.
• Women who discontinue antidepressant medication during pregnancy may have an increased risk of relapse of major depression 2.

From the Research

Zoloft (Sertraline) Use in Pregnancy

• Zoloft, also known as sertraline, is a selective serotonin reuptake inhibitor (SSRI) commonly used to treat depression and other mental health conditions.
• The safety of using Zoloft during pregnancy has been studied extensively, with some studies suggesting that it may be associated with certain risks to the fetus, while others indicate that the benefits of treatment may outweigh these risks 3, 4, 5, 6, 7.

Risks Associated with Zoloft Use in Pregnancy

• Some studies have found that Zoloft use during pregnancy may be associated with an increased risk of congenital heart defects, preterm birth, and neonatal adaptation symptoms 5, 7.
• However, other studies have found no significant increase in the risk of major congenital malformations or other adverse outcomes associated with Zoloft use during pregnancy 3, 4.
• It is essential to note that untreated depression during pregnancy can also have negative consequences for both the mother and the fetus, including increased risk of preterm birth, low birth weight, and maternal suicide 3, 4, 6.

Benefits of Zoloft Use in Pregnancy

• Zoloft may be effective in treating depression and other mental health conditions during pregnancy, which can improve maternal and fetal outcomes 3, 4, 6.
• A systematic review of meta-analyses found limited evidence that Zoloft use during pregnancy may prevent relapse in severe or recurrent depression 5.

Clinical Decision-Making

• The decision to use Zoloft during pregnancy should be made on a case-by-case basis, taking into account the individual patient's medical history, the severity of their depression, and the potential risks and benefits of treatment 3, 4, 6.
• Clinicians should carefully evaluate the patient's psychopathological condition and weigh the risks of prenatal exposure to Zoloft against the potential risks of untreated depression 4, 6.