What are the effects of Selective Serotonin Reuptake Inhibitors (SSRIs) during pregnancy?

From the Guidelines

Selective serotonin reuptake inhibitors (SSRIs) can be used during pregnancy when the benefits outweigh the risks, particularly for women with moderate to severe depression or anxiety, as the potential risks to the fetus are generally outweighed by the risks of untreated depression to both mother and baby. Common SSRIs prescribed during pregnancy include sertraline (Zoloft), which is often considered first-line at 25-200 mg daily, and fluoxetine (Prozac) at 10-80 mg daily 1. While there are some concerns about potential risks, including a small increased risk of persistent pulmonary hypertension in newborns (1-2 per 1,000 births) and a possible slight increase in the risk of birth defects with paroxetine specifically, untreated depression during pregnancy carries significant risks for both mother and baby, such as poor prenatal care, inadequate nutrition, increased substance use, preterm birth, low birth weight, and postpartum depression 1.

Some key points to consider when prescribing SSRIs during pregnancy include:

• The potential for neonatal drug withdrawal, which can manifest with symptoms such as continuous crying, irritability, jitteriness, and/or restlessness; shivering; fever; tremors; hypertonia or rigidity; tachypnea or respiratory distress; feeding difficulty; sleep disturbance; hypoglycemia; and seizures 1
• The importance of continuing SSRI treatment during pregnancy at the lowest effective dose, as withdrawal of medication may have harmful effects on the mother-infant dyad 1
• The need for early follow-up after the initial hospital discharge to monitor for potential adverse effects in the newborn 1
• The consideration of the differences among drugs in a therapeutic class vis-à-vis the ratio of human milk to maternal plasma drug concentration, the likely total daily infant drug dose, and the ratio of infant to maternal plasma drug concentration when making recommendations about lactation and breastfeeding 1

Treatment decisions should be individualized, considering the severity of the mother's condition and potential risks of medication. Women already on SSRIs who become pregnant should not abruptly discontinue their medication, as this could lead to withdrawal symptoms and depression relapse. Instead, they should consult with their healthcare provider to discuss the appropriate course of action based on their specific situation 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. 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. Infants exposed to SSRIs in pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN).

SSRI use during pregnancy may be associated with an increased risk of persistent pulmonary hypertension of the newborn (PPHN) and other complications, such as respiratory distress, cyanosis, apnea, seizures, and temperature instability.

• The decision to use sertraline during pregnancy should be made on a case-by-case basis, considering the potential benefits and risks.
• Sertraline should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus 2.
• Similar findings were observed with citalopram, another SSRI, which also carries a risk of PPHN and other complications in newborns 3.
• Physicians should carefully consider the potential risks and benefits of SSRI use during pregnancy.

From the Research

SSRIs During Pregnancy: Risks and Benefits

• The use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy has been associated with various risks, including miscarriage, premature delivery, neonatal complications, birth defects, and neurodevelopmental disorders in childhood 4, 5.
• Studies have shown that exposure to SSRIs in pregnancy may increase the risk of birth defects, specifically cardiac defects, and neurodevelopmental disorders such as autism spectrum disorders 4, 5.
• However, untreated maternal depression also carries serious risks for both the mother and the baby, and SSRIs are one of the best available treatments 5, 6.
• The risk-benefit balance of SSRI use during pregnancy should be carefully considered, taking into account the potential risks and benefits of treatment, as well as the risks of untreated depression 6, 7.

Specific Risks Associated with SSRI Use During Pregnancy

• Maternal SSRI treatment during the first trimester has been implicated in increased risks of birth defects, specifically cardiac abnormalities, in the infant 5.
• Third-trimester treatment has been linked to various neonatal complications, including symptoms of neonatal withdrawal and toxicity, prematurity, low birth weight, and persistent pulmonary hypertension of the newborn 5.
• SSRI use during pregnancy has also been associated with an increased risk of preterm birth, with a systematic review and meta-analysis finding a significantly higher incidence of preterm birth in women treated with SSRIs compared to controls 8.

Management of SSRI Use During Pregnancy

• Pregnant women exposed to any SSRI in early pregnancy should be offered options for prenatal diagnosis through ultrasound examinations and fetal echocardiography to detect the presence of birth defects 4.
• Tapering off or switching to other therapy in early pregnancy, if appropriate for the individual, may also be considered on a case-by-case basis 4.
• Treatment with SSRIs before and during pregnancy should only be considered in case of real necessity, and milder forms of depression should be treated with alternative methods 7.