A 29-year-old woman at 10 weeks gestation is seen for follow-up of moderate major depressive disorder. Her PHQ-9 is 16 and she meets criteria for pharmacologic treatment. She has never taken an antidepressant before. Chart review shows normal prenatal labs and no prior psychiatric hospitalizations. Which of the following is the most appropriate first-line antidepressant?

Question

Accepted Answer

✅ C. Sertraline
Sertraline is the preferred SSRI in pregnancy. It has the largest body of real-world safety data, low placental transfer compared with other SSRIs, and is also preferred during lactation due to minimal infant serum levels. Untreated moderate-to-severe depression in pregnancy carries its own risks (preterm birth, low birth weight, impaired bonding, postpartum depression), so SSRI therapy is appropriate when indicated. Shared decision-making with the patient is standard.

❌ A. Paroxetine
Paroxetine is AVOIDED in pregnancy. First-trimester exposure has been associated with a small increase in cardiac malformations (particularly ventricular septal defects), and it has historically been classified category D. It is generally the one SSRI to explicitly avoid when initiating therapy in pregnancy.

❌ B. Bupropion
Bupropion is not a first-line agent in pregnancy for depression primarily because it lowers seizure threshold and the safety database is smaller than for SSRIs. It may be considered when smoking cessation is an additional goal or when SSRIs have failed, but it is not the first choice here.

❌ D. Venlafaxine
Venlafaxine (an SNRI) is not first-line in pregnancy. SNRIs are associated with neonatal adaptation syndrome (jitteriness, respiratory distress, feeding difficulty after delivery) and maternal hypertension. SSRIs — especially sertraline — are preferred as initial therapy.

:::pearl
Pregnancy SSRI of choice: SERTRALINE. Avoid PAROXETINE (cardiac defects). Fluoxetine is acceptable but has the longest half-life, meaning more neonatal exposure at delivery. Untreated depression is not benign — treat when clinically indicated.
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