Which selective serotonin reuptake inhibitors (SSRIs) and other antidepressants are considered safe for use during pregnancy, and what are the recommended starting doses?

Antidepressants Safe in Pregnancy

Sertraline should be considered the first-line antidepressant during pregnancy, with starting doses of 25-50 mg daily, titrated slowly while monitoring the newborn. 1

Primary Recommendation: Sertraline

Sertraline is the preferred SSRI during pregnancy and breastfeeding due to its minimal excretion in breast milk (providing infants with less than 10% of maternal daily dose) and low infant-to-maternal plasma concentration ratios. 1 Large population-based studies have demonstrated no increased risk of cardiac malformations with first-trimester sertraline use. 1

Dosing Strategy

• Start at 25-50 mg daily 1
• Titrate slowly upward as needed 1
• Use the lowest effective dose throughout pregnancy 1

Key Safety Points

• Continue treatment through pregnancy rather than discontinuing, as withdrawal carries significant risks including increased relapse of major depression, premature birth, decreased breastfeeding initiation, and harm to the mother-infant relationship. 1
• Third-trimester exposure may cause transient neonatal adaptation symptoms (irritability, jitteriness, tremors, feeding difficulty, sleep disturbance, respiratory distress) appearing within hours to days after birth, typically resolving within 1-2 weeks. 1
• The possible association with persistent pulmonary hypertension of the newborn (PPHN) has a number needed to harm of 286-351, representing a very small absolute risk. 1

Alternative SSRI: Citalopram

If sertraline is not tolerated or ineffective, citalopram should be considered as the second-line SSRI. 1

Non-SSRI Options

Bupropion (First-Line Non-SSRI)

Bupropion is the primary non-SSRI antidepressant option for pregnancy, particularly useful for patients with co-occurring ADHD or those requiring an alternative to SSRIs. 2, 3

Dosing

• SR formulation: Start 100-150 mg daily, maintenance 100-150 mg twice daily 2, 3
• XL formulation: Start 150 mg daily, maintenance 150-300 mg daily 2, 3
• Maximum dose: 450 mg per day 2, 3

Safety Profile

• Does not appear associated with major congenital malformations or significant adverse obstetrical outcomes in most studies 2, 3
• Small absolute increase in two specific cardiovascular malformations reported (left ventricular outflow tract obstruction and ventricular septal defects), but confounding by indication cannot be ruled out and other studies have not replicated these findings 2, 3
• Possible increased risk for spontaneous abortion, though confounding by indication is likely 2

Breastfeeding Considerations

• Very limited data (21 cases) 2
• Present in breast milk at very low levels, sometimes undetectable 2
• Two case reports of seizures in breastfed infants exist, though causality uncertain 2, 1
• Generally no adverse events reported in most cases 1

Atomoxetine (Alternative for ADHD-Related Depression)

Atomoxetine serves as an alternative for patients with ADHD and comorbid depression. 3

Dosing

• Start 40 mg daily 2, 3
• Adjust every 7-14 days to 60 mg, then 80 mg 2, 3
• Maximum: lesser of 1.4 mg/kg/day or 100 mg/day 2, 3

Safety Profile

• Does not appear associated with major congenital malformations, including cardiac malformations 2, 3
• Possible increased risk for spontaneous abortion, though confounding by indication cannot be ruled out 2, 3
• Recent large, well-controlled study demonstrated no increased risks for long-term neurodevelopmental outcomes 2

Breastfeeding Considerations

• Caution advised: No published studies on atomoxetine while breastfeeding 2
• Based on pharmacokinetics (low molecular weight, long half-life), likely present in human milk with unknown effects on nursing infants 2

Medications to Avoid

Paroxetine should be avoided in pregnancy due to FDA pregnancy category D classification and demonstrated increased risk of cardiac malformations. 1

Fluoxetine carries higher risk than sertraline and should not be first-line, though it does not appear to cause autism spectrum disorder or ADHD (observed associations are due to confounding factors). 1

Critical Monitoring Requirements

During Pregnancy

• Serial ultrasound examinations for fetal growth 3
• Maternal blood pressure monitoring 1
• Appropriate maternal weight gain assessment 1

Neonatal Period

• Arrange early follow-up after initial hospital discharge 1
• Monitor for signs of drug toxicity or withdrawal over first week of life 1
• Watch for irritability, insomnia, feeding difficulty, jitteriness, tremors, respiratory distress 1
• In severely affected infants with persistent symptoms, short-term chlorpromazine has provided measurable relief 1
• Monitor for adequate weight gain and developmental milestone achievement 1

Neurodevelopmental Outcomes

Converging evidence from multiple study designs demonstrates that observed associations between prenatal antidepressant exposure and neurodevelopmental problems (autism spectrum disorder, ADHD) are largely due to confounding factors such as maternal psychiatric illness rather than causal medication effects. 1, 4 Several recent reviews have not identified adverse neurodevelopmental outcomes among infants born to women treated with SSRIs during pregnancy. 1

Clinical Decision Algorithm

1. For depression without ADHD: Start sertraline 25-50 mg daily 1
2. If sertraline not tolerated: Switch to citalopram 1
3. For depression with ADHD or requiring non-SSRI: Consider bupropion SR 100-150 mg daily 3
4. For ADHD with comorbid depression: Consider atomoxetine 40 mg daily 3
5. Never discontinue treatment abruptly: Continue at lowest effective dose through pregnancy 1
6. If switching from paroxetine: Transition directly to sertraline without washout period to prevent depressive relapse 1

Common Pitfalls to Avoid

• Do not discontinue antidepressants due to fear of medication risks: Untreated maternal depression carries substantial documented risks to both mother and infant, including preterm birth, poor maternal-infant bonding, and increased maternal substance use. 1, 5
• Do not use paroxetine or fluoxetine as first-line agents: These carry higher risks than sertraline. 1, 4
• Do not fail to counsel about transient neonatal adaptation symptoms: These are common but self-limited and should not deter necessary treatment. 1
• Do not combine multiple serotonergic agents without careful monitoring: Risk of serotonin syndrome increases substantially. 6