What are the options for antidepressants in pregnancy?

Antidepressant Options in Pregnancy

First-Line Recommendation

Sertraline is the preferred first-line antidepressant for pregnant women requiring pharmacological treatment, due to minimal breast milk excretion, low infant-to-maternal plasma ratios, and no demonstrated increased risk of cardiac malformations in large population studies. 1, 2

Treatment Algorithm by Depression Severity

Mild Depression (Recent Onset)

• Begin with monitoring, exercise, and social support before initiating medication 3
• If symptoms persist beyond 2 weeks, escalate to evidence-based treatment 3
• Consider cognitive therapy as first-line for mild-to-moderate depression, which is roughly equally effective as antidepressants 3

Moderate-to-Severe Depression

• Antidepressants are recommended as first-line pharmacological treatment 3
• SSRIs are the most commonly prescribed class for pregnant women 3
• Start sertraline at 25-50 mg daily and titrate slowly while monitoring the newborn 1

High-Risk Scenarios Requiring Antidepressants

• History of severe suicide attempts or severe depression with good prior medication response 3
• Previous relapse when discontinuing antidepressant treatment 3
• Failed psychotherapy without adequate symptom reduction 3

Specific SSRI Recommendations

Preferred Agents

• Sertraline: First-line choice - provides infant with less than 10% of maternal daily dose through breast milk, can be continued during breastfeeding 1
• Paroxetine: Alternative first-line for breastfeeding - transfers to breast milk in lower concentrations than other antidepressants 3, 2
• Citalopram: Second-line alternative if sertraline is not tolerated or ineffective 1

Agents to Avoid

• Paroxetine should be avoided in first trimester due to FDA pregnancy category D classification and cardiac malformation concerns 1
• Fluoxetine should be avoided due to higher risk for birth defects and cardiac defects 4, 5

Alternative Non-SSRI Option

Bupropion

• Can be considered for co-occurring depression, particularly if SSRIs are not tolerated 1
• FDA data shows no increased risk of congenital malformations overall in 675 first-trimester exposures from international Pregnancy Registry 6
• Cardiovascular malformation rate of 1.3% is similar to background rate of approximately 1% 6
• Very limited breastfeeding data (only 21 cases) with two case reports of seizures in breastfed infants, though causality uncertain 1
• Less efficacious than SSRIs for anxiety disorders 1

Critical Safety Information

Neonatal Adaptation Syndrome

• Occurs in approximately 30% of third-trimester SSRI exposures 3
• Symptoms include crying, irritability, tremors, poor feeding, hypertonia, tachypnea, sleep disturbance, hypoglycemia 3
• Typically self-limiting, resolving within 1-4 weeks 3, 1
• Arrange early follow-up after hospital discharge and monitor infants over first week of life 1
• In severely affected infants with persistent symptoms, short-term chlorpromazine has provided relief 1

Persistent Pulmonary Hypertension of the Newborn (PPHN)

• Late pregnancy SSRI exposure has possible association with PPHN 1
• Number needed to harm: 286-351 3, 1
• FDA revised 2006 advisory in 2011 stating conflicting findings make it unclear whether SSRIs cause PPHN 3

Neurodevelopmental Outcomes

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

Other Pregnancy Risks

• Antidepressant use may increase risk of preterm delivery compared to untreated depressed women 3
• No increased risk of cardiac malformations with first-trimester sertraline use in large population-based studies 1

Critical Treatment Principles

Continue Treatment Through Pregnancy

• SSRI treatment should be continued during pregnancy at the lowest effective dose 1
• Withdrawal of medication may have harmful effects on the mother-infant dyad 1
• Women who discontinued antidepressants during pregnancy were more likely to experience relapse than those who continued 6

Risks of Untreated Depression

• Premature birth 3
• Decreased initiation of breastfeeding 3
• Harm to mother-infant relationship 1
• Untreated maternal depression carries substantial documented risks to both mother and infant 1

Treatment Duration

• Continue for at least 4-9 months after satisfactory response for first episode 2
• For recurrent depression, treatment beyond initial 4-9 months may be beneficial 2
• If no adequate response within 6-8 weeks, modify treatment 2

Monitoring Requirements

Maternal Monitoring

• About two-thirds of patients receiving SSRIs experience at least one adverse effect 2
• Nausea and vomiting are most common reasons for discontinuation 2
• Regular follow-up essential to assess treatment response and adjust dosage 2

Infant Monitoring

• Monitor breastfed infants for irritability, poor feeding, sleep disturbances 2
• Watch for signs of drug toxicity or withdrawal over first week of life 1

Common Pitfalls to Avoid

• Do not discontinue treatment due to fear of medication risks - untreated depression carries greater documented risks 1
• Do not use paroxetine in first trimester despite its favorable breastfeeding profile 1
• Do not avoid breastfeeding if already taking sertraline - benefits of breastfeeding are well-documented and risks are minimal 1
• Do not fail to screen - screen all pregnant women for depression using validated tools (PHQ, HADS, Edinburgh Postnatal Depression Scale) 3