Is sertraline (Zoloft) safe during pregnancy?

From the Guidelines

Sertraline (Zoloft) is considered a relatively safe option for pregnant women with moderate to severe depression or anxiety disorders, as the benefits often outweigh the potential risks 1. When considering the use of sertraline during pregnancy, it's essential to weigh the individual factors, including the severity of depression, previous response to treatment, and personal medical history, in consultation with both an obstetrician and mental health provider.

• Typical dosing ranges from 50-200mg daily, with treatment continuing throughout pregnancy if needed.
• Women should not stop taking sertraline suddenly upon discovering pregnancy, as untreated depression carries significant risks for both mother and baby, including poor prenatal care, inadequate nutrition, increased substance use, and pregnancy complications.
• Some studies suggest a small increased risk of certain birth defects with first-trimester exposure, though the absolute risk remains very low 1.
• There may also be a slight risk of neonatal adaptation syndrome (temporary jitteriness, irritability, or feeding difficulties) in newborns when sertraline is taken late in pregnancy.
• Recent research has shown that intrauterine antidepressant exposure does not substantially increase the risk for neurodevelopmental problems, such as ASD and ADHD 1.
• The American Psychiatric Association and the American College of Obstetricians and Gynecologists recommend a stepped approach to treatment of depression during pregnancy, considering severity of current symptoms, previous mental health history, and patient treatment preferences 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 during pregnancy is associated with potential risks, including:

• Delayed ossification in fetuses
• Increased risk of stillborn pups and pup mortality
• Decreased pup body weights
• Complications in neonates, such as respiratory distress, cyanosis, and seizures
• Potential increased risk of persistent pulmonary hypertension of the newborn (PPHN) However, there are also benefits to consider, including the treatment of depression in pregnant women. The decision to use sertraline during pregnancy should be made on a case-by-case basis, weighing the potential benefits against the potential risks 2.

From the Research

Safety of Sertraline During Pregnancy

• The safety of sertraline during pregnancy is a topic of ongoing debate, with various studies providing different conclusions 3, 4, 5.
• A meta-review of meta-analyses found that sertraline was associated with an increased risk of congenital heart defects, but not major congenital malformations 3.
• Another study found that sertraline had a mixed association with negative outcomes, but this association was generally unsubstantiated when controlled for maternal depression and associated factors 5.
• A review of the literature found that sertraline and citalopram should be considered first-line drug treatments for anxiety and depression in pregnant women in the SSRI class, due to their relatively safer profiles compared to other SSRIs 5.

Comparison with Other SSRIs

• Paroxetine and fluoxetine have been found to have a stronger association with negative outcomes, such as significant malformations, persistent pulmonary hypertension of the newborn (PPHN), and neonatal abstinence syndrome (NAS) 3, 4, 5.
• The safety of escitalopram and fluvoxamine is less well-studied, with too few studies to draw definite conclusions 5.

Clinical Implications

• The use of antidepressants during pregnancy should be carefully considered, taking into account the potential risks and benefits 6, 3, 7.
• Clinicians should be aware of the different safety profiles of various SSRIs and consider these when making treatment decisions for pregnant women with anxiety and depression 5.
• Further research is needed to fully understand the safety of sertraline and other SSRIs during pregnancy, as well as to develop clinical protocols for treating anxiety and depression in pregnant women 5.