What are the guidelines for using Selective Serotonin Reuptake Inhibitors (SSRIs), such as Lexapro (escitalopram), in a female patient of childbearing age with a history of depression or anxiety who is pregnant or planning to become pregnant?

SSRI Use During Pregnancy

Sertraline should be the first-line SSRI for pregnant women or those planning pregnancy, used at the lowest effective dose, and continued throughout pregnancy and breastfeeding rather than discontinued. 1, 2

First-Line Agent Selection

• Sertraline is the preferred SSRI due to minimal excretion in breast milk, low infant-to-maternal plasma concentration ratios, and the most favorable safety profile among SSRIs. 1, 2
• Citalopram can be considered as a second-line alternative if sertraline is not tolerated or ineffective. 1
• Avoid paroxetine specifically - it carries FDA pregnancy category D classification due to cardiac malformation concerns and has the strongest association with negative outcomes. 3, 4
• Escitalopram (Lexapro) has limited pregnancy data compared to sertraline, though the FDA label acknowledges use during pregnancy requires careful risk-benefit assessment. 5, 4

Treatment Decision Algorithm

For mild depression with recent onset:

• Begin with monitoring, exercise, and social support before initiating pharmacological treatment. 3
• If no improvement within two weeks, proceed to evidence-based treatment. 3

For moderate-to-severe depression:

• Antidepressants are recommended as first-line treatment alongside or instead of psychotherapy. 3
• Consider antidepressants for women with history of severe suicide attempts, severe depression with prior medication response, or previous relapse when discontinuing treatment. 3

Critical principle: Continue SSRI treatment during pregnancy at the lowest effective dose rather than discontinuing, as withdrawal may have harmful effects on the mother-infant dyad. 1, 2

Risks of SSRI Use During Pregnancy

Third-trimester exposure (Neonatal Adaptation Syndrome):

• Occurs in approximately 30% of third-trimester exposures, presenting with irritability, jitteriness, tremors, feeding difficulty, sleep disturbance, respiratory distress, crying, hypertonia, tachypnea, and hypoglycemia. 1, 3
• Symptoms typically appear within hours to days after birth and are self-limiting, resolving within 1-4 weeks. 1, 3
• In severely affected infants with persistent symptoms, short-term chlorpromazine has provided measurable relief. 1

Persistent Pulmonary Hypertension of the Newborn (PPHN):

• Late pregnancy SSRI exposure has a possible association with PPHN, with number needed to harm of 286-351. 1, 2, 3
• The FDA revised its 2006 advisory in 2011, stating conflicting findings make it unclear whether SSRIs cause PPHN. 3

Cardiac malformations:

• Large population-based studies have demonstrated no increased risk of cardiac malformations with first-trimester sertraline use. 1, 2, 3
• Paroxetine and fluoxetine show stronger associations with cardiac defects and should be avoided. 3, 4

Neurodevelopmental outcomes:

• Several recent reviews have not identified adverse neurodevelopmental outcomes among infants born to women treated with SSRIs during pregnancy. 1
• Recent evidence provides reassurance that antidepressant use is unlikely to substantially increase risk of autism spectrum disorder or ADHD. 3

Risks of Untreated Depression

Maternal and fetal consequences of untreated depression include:

• Premature birth and preterm delivery. 1, 2, 3
• Decreased breastfeeding initiation. 1, 2, 3
• Harm to the mother-infant relationship. 1

The documented risks of untreated maternal depression are substantial and must be weighed against medication risks. 1, 2

Breastfeeding Recommendations

• Sertraline should be continued during breastfeeding as it transfers in very low concentrations into breast milk, providing the infant with less than 10% of the maternal daily dose. 1, 2, 3
• Sertraline and paroxetine are the most commonly prescribed antidepressants during breastfeeding, though sertraline is preferred given paroxetine's pregnancy concerns. 1, 3
• Start with low doses (25-50 mg daily) and slowly titrate upward while monitoring the newborn. 1
• Monitor breastfed infants for excess sedation, restlessness, agitation, poor feeding, and poor weight gain. 5

Monitoring and Follow-up

• Arrange early follow-up after initial hospital discharge for infants exposed to SSRIs in the third trimester. 1, 2
• Monitor infants for signs of drug toxicity or withdrawal over the first week of life. 1
• Screen all pregnant women for depression using validated tools (Patient Health Questionnaire, Hospital Anxiety and Depression Scale, or Edinburgh Postnatal Depression Scale). 3
• Monitor maternal mental health closely throughout pregnancy. 2

Critical Pitfalls to Avoid

• Do not discontinue SSRI treatment abruptly - this poses significant relapse risk and withdrawal symptoms including anxiety, irritability, mood changes, headache, sweating, nausea, dizziness, and electric shock-like sensations. 5
• Do not avoid treatment altogether due to fear of medication risks - untreated maternal depression carries substantial documented risks to both mother and infant. 1, 2
• Do not switch from sertraline to escitalopram during pregnancy without compelling clinical reason, as sertraline has more robust safety data. 1, 4
• Escitalopram use later in pregnancy may lead to increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, tube feeding, and/or PPHN. 5