Is citalopram (Celexa) safe to use during pregnancy?

Citalopram Use During Pregnancy

Citalopram can be used during pregnancy when clinically indicated, as the benefits of treating maternal depression generally outweigh the potential risks to the fetus, though it should be used at the lowest effective dose with awareness of neonatal adaptation syndrome risk in late pregnancy. 1

Risk-Benefit Assessment

The FDA classifies citalopram as Pregnancy Category C, meaning there are no adequate and well-controlled studies in pregnant women, and the drug should be used only if potential benefits justify potential risks to the fetus. 1 However, clinical guidelines emphasize that untreated severe depression during pregnancy poses significant risks that often exceed the minimal risks associated with antidepressant use. 2

Risks of Untreated Depression

• Untreated depression is associated with premature birth, decreased breastfeeding initiation, and harmful effects on the mother-infant relationship 3
• Women who discontinued antidepressants during pregnancy showed significantly increased relapse rates of major depression compared to those who continued treatment 1
• The American Psychiatric Association and American College of Obstetricians and Gynecologists recommend that women with severe depression who previously responded to antidepressants should continue treatment during pregnancy 4, 2

Fetal and Neonatal Safety Profile

Congenital Malformations

• Animal studies showed teratogenic effects only at maternally toxic doses approximately 18 times the maximum recommended human dose, with no effects observed in rabbits 1
• A prospective study of 132 pregnant women exposed to citalopram found only 1 major malformation (0.9%) among 108 live-born infants exposed in the first trimester, which is not significantly elevated above baseline rates 5
• Citalopram use during embryogenesis is not associated with apparent major teratogenic risk 5
• Current evidence suggests citalopram and sertraline can be used during pregnancy, with reassuring safety data 6, 7

Neonatal Adaptation Syndrome

• Third-trimester exposure carries risk of neonatal adaptation syndrome, presenting with respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, jitteriness, irritability, and constant crying 1
• These complications can arise immediately upon delivery and may require prolonged hospitalization, respiratory support, and tube feeding 1
• A prospective study found a 4.2-fold increased risk (95% CI 1.71-10.26) of special-care nursery admission for neonates exposed to citalopram close to term 5
• Symptoms typically resolve within 1-2 weeks and represent either direct drug effects or withdrawal syndrome 3

Persistent Pulmonary Hypertension of the Newborn (PPHN)

• SSRI exposure may increase PPHN risk, though epidemiologic studies show conflicting results 1
• PPHN occurs in 1-2 per 1,000 live births in the general population and carries substantial morbidity and mortality 1

Clinical Management Recommendations

Dosing Strategy

• Use the lowest effective dose throughout pregnancy 3, 1
• Standard initial dose is 20 mg once daily, with maximum of 40 mg/day 1
• Doses above 40 mg/day are not recommended due to QT prolongation risk 1
• Therapeutic drug monitoring should be considered to minimize fetal exposure, as pregnancy induces CYP2D6 metabolism, potentially lowering drug levels 8

Treatment Decision Algorithm

1. For women with mild depression of recent onset (<2 weeks): Monitor and encourage exercise and social support 4
2. For women with mild depression not improving within 2 weeks or moderate-to-severe depression: Offer evidence-based treatment 4
3. For women with history of severe depression or suicide attempts who previously responded to antidepressants: Continue medication during pregnancy 4, 2
4. For women who relapsed when discontinuing antidepressants previously: Continue treatment during pregnancy 4
5. For women already on citalopram when pregnancy is discovered: Continue at lowest effective dose if clinically indicated 3, 1

Monitoring Requirements

• Arrange early follow-up after hospital discharge to monitor newborns for adaptation syndrome 3
• Monitor maternal symptoms closely, with follow-up within 1-2 weeks after any medication changes 2
• Consider adding cognitive behavioral therapy, which has similar effectiveness to antidepressants and can be used in combination 4, 2

Third Trimester Considerations

• When treating during the third trimester, carefully weigh potential risks against benefits, but do not automatically discontinue effective treatment 1
• Inform neonatal care team of maternal SSRI use to ensure appropriate monitoring at delivery 3
• Be prepared for potential neonatal complications requiring short-term management 3

Common Pitfalls to Avoid

• Do not abruptly discontinue citalopram: Gradual dose reduction is recommended to avoid withdrawal symptoms in the mother 1
• Do not assume all SSRIs have identical safety profiles: Paroxetine and fluoxetine have stronger associations with negative outcomes compared to citalopram and sertraline 7
• Do not overlook the need for dose adjustment: Pregnancy-induced metabolic changes may require therapeutic drug monitoring 8
• Do not fail to document shared decision-making: Treatment decisions must consider depression severity, previous mental health history, and patient preferences 4

Comparative Evidence Quality

Recent systematic reviews provide reassurance that prenatal antidepressant exposure is unlikely to substantially increase risk of neurodevelopmental problems like autism spectrum disorder or ADHD, with observed associations largely explained by confounding factors rather than direct drug effects 4. Growing evidence from studies assessing unmeasured confounding suggests that associations between prenatal antidepressant exposure and adverse outcomes are largely explained by maternal illness and associated factors rather than medication exposure itself. 4

Human observational data is more reassuring than animal studies, and citalopram and sertraline should be considered first-line SSRI treatments for depression in pregnant women based on their favorable safety profiles. 7