In a pregnant woman with depression or anxiety, what is the recommended selective serotonin reuptake inhibitor (SSRI) choice, dosing, and overall management strategy, including considerations for continuation, initiation, avoidance of paroxetine, psychotherapy, alternative agents, and breastfeeding?

SSRI Use in Pregnancy for Depression and Anxiety

First-Line Agent

Sertraline should be the first-line SSRI for treating depression and anxiety in pregnant women due to its well-established safety profile, minimal breast milk excretion, and low infant-to-maternal plasma concentration ratios. 1

Medication Selection Algorithm

Preferred Agent

• Sertraline is recommended as first-line therapy based on:
  • No demonstrated increased risk of cardiac malformations in large population-based studies 1
  • Minimal excretion in breast milk (infant receives <10% of maternal daily dose) 1
  • Well-established safety profile with extensive clinical experience 1, 2

Alternative Agent

• Citalopram can be considered if sertraline is not tolerated or ineffective 1
• Both sertraline and citalopram have mixed and generally unsubstantiated associations with negative outcomes when controlled for maternal depression 3

Agent to Avoid

• Paroxetine must be avoided due to FDA pregnancy category D classification and documented increased risk of cardiac malformations 1, 4
• The FDA label specifically warns of 2- to 3-fold increased risk of right ventricular outflow tract obstructions 4
• If a patient is already taking paroxetine, transition directly to sertraline without a washout period to prevent depressive relapse 1

Treatment Continuation vs. Discontinuation

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, 5

Evidence Supporting Continuation

• Women who discontinue antidepressants during pregnancy show significantly increased relapse risk of major depression 1, 4
• Untreated depression carries substantial risks including premature birth, decreased breastfeeding initiation, and harm to the mother-infant relationship 1, 2

Indications for Continuation

• Women with severe depression or history of relapse when discontinuing treatment should continue antidepressant use 1
• Women with history of severe suicide attempts or severe depression who previously responded well to medication 2
• Women who have previously relapsed when discontinuing antidepressant treatment 2

Dosing Strategy

• Start with 25-50 mg daily of sertraline and slowly titrate upward while carefully monitoring 1
• Use the lowest effective dose throughout pregnancy and postpartum 1
• Maintain steady dosing rather than tapering in third trimester 5

Risk-Benefit Considerations

Risks of SSRI Treatment

Third-trimester exposure risks (manageable and typically self-limiting):

• Neonatal adaptation syndrome occurs in approximately 30% of third-trimester exposures 2
• Symptoms include irritability, jitteriness, tremors, feeding difficulty, sleep disturbance, respiratory distress, hypoglycemia 1, 5
• Symptoms typically appear within hours to days after birth and resolve within 1-4 weeks 1, 2

Rare but serious risks:

• Persistent Pulmonary Hypertension of the Newborn (PPHN) with late pregnancy exposure has a number needed to harm of 286-351 1, 2
• This represents a small absolute risk increase from baseline PPHN rate of 1-2 per 1000 live births 6, 4

Reassuring neurodevelopmental data:

• Multiple reviews have not identified adverse neurodevelopmental outcomes among infants born to women treated with SSRIs during pregnancy 1, 5
• Converging evidence suggests associations between prenatal antidepressant exposure and autism spectrum disorder or ADHD are largely due to confounding factors (maternal psychiatric illness) rather than causal medication effects 1, 2

Risks of Untreated Depression

• Premature birth 1, 2
• Decreased breastfeeding initiation 1, 2
• Maternal morbidity including hypertension, preeclampsia 7
• Suicide attempts and ideation 7
• Negative impact on infant emotional development 8

Psychotherapy Considerations

Evidence-based psychotherapies (such as cognitive therapy) are roughly equally effective as antidepressants for treating depression and should be considered first-line treatment for mild-to-moderate depression. 2

Treatment Algorithm by Severity

Mild depression with recent onset:

• Begin with monitoring, encourage exercise and social support 2
• If no improvement within 2 weeks, offer evidence-based treatment 2

Moderate-to-severe depression:

• Consider antidepressants as first-line treatment 2
• Psychotherapy alone may be insufficient 2

Women who have tried psychotherapy without adequate symptom reduction:

• Should be considered for antidepressants 2

Breastfeeding Management

Continue sertraline during breastfeeding—do not discontinue either breastfeeding or medication. 1

• Sertraline transfers to breast milk in very low concentrations 1, 2
• Both sertraline and paroxetine are considered suitable first-line agents during lactation, though paroxetine should be avoided in pregnancy 1
• Benefits of breastfeeding for both mother and infant are well-documented, and untreated maternal anxiety/depression poses significant risks 1

Monitoring and Follow-up

Neonatal Monitoring

• Arrange early follow-up after initial hospital discharge for infants exposed to SSRIs 1
• Monitor infants for signs of drug toxicity or withdrawal over the first week of life 1, 5
• Inform pediatric team about maternal sertraline use so they can anticipate and manage neonatal adaptation syndrome 5

Specific Signs to Monitor

• Irritability, feeding difficulties, respiratory symptoms 5
• Crying, tremors, poor feeding, hypertonia, tachypnea, sleep disturbance, hypoglycemia 2, 5

Management of Severe Symptoms

• In severely affected infants with persistent symptoms, a short-term course of chlorpromazine has provided measurable relief 1

Screening Recommendations

Screen all pregnant women for depression using validated tools such as the Patient Health Questionnaire, Hospital Anxiety and Depression Scale, or Edinburgh Postnatal Depression Scale 2

Common Pitfalls to Avoid

• Do not discontinue treatment due to fear of medication risks—untreated maternal depression carries substantial documented risks to both mother and infant 1
• Do not use paroxetine in pregnancy or switch to it from another agent 1, 4
• Do not taper or discontinue SSRIs in third trimester in an attempt to avoid neonatal adaptation syndrome—this increases maternal relapse risk without eliminating neonatal symptoms 5
• Do not avoid treatment altogether in women with moderate-to-severe depression—the risks of untreated illness outweigh medication risks 2, 9