Is Prozac (fluoxetine) safe to use during pregnancy, especially in women with a history of depression?

Is Prozac Safe During Pregnancy?

Prozac (fluoxetine) can be used during pregnancy when clinically indicated, particularly for women with moderate-to-severe depression or those with a history of severe depression who previously responded well to medication, though it carries some risks that require careful consideration. 1

When Prozac Should Be Used

The decision to use Prozac during pregnancy depends primarily on depression severity:

• For moderate-to-severe depression, antidepressants including fluoxetine are recommended by the American College of Obstetricians and Gynecologists, as the benefits typically outweigh the risks 1, 2
• Women with a history of severe suicide attempts or severe depression who previously responded well to medication should continue treatment during pregnancy 1
• Women who have previously relapsed when discontinuing antidepressants should be considered for continued treatment 1
• For mild, recent-onset depression, begin with monitoring, exercise, and social support before initiating pharmacological treatment 1

Safety Profile and Risks

Teratogenic Risk (Birth Defects)

• The FDA label indicates no evidence of teratogenicity in animal studies at doses up to 1.5 times the maximum recommended human dose 3
• Fluoxetine is classified as FDA Pregnancy Category C, meaning it should be used only if potential benefit justifies potential risk to the fetus 3
• Some older studies suggested possible associations with cardiovascular malformations, though this remains controversial 4, 5
• A prospective study of 228 pregnant women taking fluoxetine found no significant increase in major structural anomalies (5.5% vs 4.0% in controls) 6

Third Trimester Complications

Third trimester exposure to fluoxetine carries specific risks that require monitoring:

• Neonatal adaptation syndrome occurs in approximately 30% of third-trimester exposures, presenting with crying, irritability, tremors, poor feeding, hypertonia, tachypnea, sleep disturbance, and hypoglycemia 1
• These symptoms are typically self-limiting and resolve within 1-4 weeks 1
• Women taking fluoxetine in the third trimester have increased risk for premature delivery (relative risk 4.8), admission to special-care nurseries (relative risk 2.6), and poor neonatal adaptation including respiratory difficulty and jitteriness (relative risk 8.7) 6
• The FDA revised its advisory on persistent pulmonary hypertension of the newborn (PPHN) in 2011, stating that conflicting findings make it unclear whether SSRIs cause PPHN 1
• A meta-analysis found the number needed to harm for PPHN is 286 to 351 1

Reassuring Long-Term Data

• Recent evidence provides reassurance that antidepressant use during pregnancy is unlikely to substantially increase the risk of autism spectrum disorder or ADHD 1

Preferred SSRI Alternatives

While fluoxetine can be used, other SSRIs may be preferable:

• SSRIs are the most commonly prescribed antidepressants for pregnant women 1
• Sertraline is often preferred as it transfers to breast milk in lower concentrations than other antidepressants 1
• Citalopram and sertraline are recommended as first-line options during pregnancy based on current data 5

Risks of Untreated Depression

The risks of untreated depression must be weighed against medication risks:

• Depression during pregnancy is associated with premature birth and decreased initiation of breastfeeding 1
• Untreated depression carries risks of maternal morbidity, including arterial hypertension, preeclampsia, suicidal ideation, and postpartum depression 4
• Women who discontinued antidepressants during pregnancy were more likely to experience relapse of major depression than those who continued medication 3

Clinical Decision Algorithm

1. Assess depression severity using validated tools (Patient Health Questionnaire, Hospital Anxiety and Depression Scale, or Edinburgh Postnatal Depression Scale) 1
2. For mild depression: Start with psychotherapy, exercise, and social support; monitor for 2 weeks 1
3. For moderate-to-severe depression or history of severe depression: Consider antidepressants, with fluoxetine as an acceptable option 1, 2
4. If already on fluoxetine pre-pregnancy with good response: Continue treatment, as discontinuation risks relapse 1, 3
5. Inform patients about neonatal adaptation syndrome risk (30% with third trimester exposure) but emphasize symptoms are self-limiting 1
6. Monitor closely in third trimester for preterm labor and prepare neonatal team for possible adaptation issues 6

Breastfeeding Considerations

• Fluoxetine is excreted in breast milk and nursing while on Prozac is not recommended per FDA labeling 3
• Sertraline or paroxetine are preferred during breastfeeding due to lower transfer to breast milk 1
• One case report documented an infant developing crying, sleep disturbance, vomiting, and watery stools while nursing from a mother on fluoxetine 3