Is fluoxetine (Prozac) safe during pregnancy?

From the Guidelines

Prozac (fluoxetine) can be used during pregnancy, but it is crucial to weigh the benefits against the potential risks, and the decision should be made in consultation with both an obstetrician and a psychiatrist. The use of Prozac during pregnancy has been studied extensively, and while it is considered one of the safer antidepressant options, it still carries some risks, such as a small increased risk of birth defects, particularly heart defects, when taken in the first trimester 1. Additionally, there is a potential risk of neonatal adaptation syndrome in newborns when Prozac is taken late in pregnancy, which can cause temporary symptoms like irritability, feeding difficulties, and respiratory distress 2.

Some key points to consider when making a decision about using Prozac during pregnancy include:

• The severity of current symptoms and previous mental health history
• Patient treatment preferences
• The potential risks and benefits of treatment
• The importance of not stopping Prozac suddenly, as this could lead to withdrawal symptoms and worsening depression 2
• The need for close monitoring and follow-up with healthcare providers to develop an appropriate treatment plan based on the specific situation and mental health needs 1

It is also important to note that untreated depression during pregnancy can pose significant risks to both mother and baby, including poor prenatal care, inadequate nutrition, increased substance use, and complications during delivery 1. Therefore, it is essential to work with healthcare providers to determine the best course of treatment and to carefully monitor the use of Prozac during pregnancy. Recent research suggests that intrauterine antidepressant exposure does not substantially increase the risk for neurodevelopmental problems, such as ASD and ADHD 1, which can provide reassurance for women considering antidepressant use during pregnancy.

From the FDA Drug Label

Pregnancy Category C In embryo–fetal development studies in rats and rabbits, there was no evidence of teratogenicity following administration of up to 12.5 and 15 mg/kg/day, respectively (1.5 and 3. 6 times, respectively, the MRHD of 80 mg on a mg/m2 basis) throughout organogenesis. However, in rat reproduction studies, an increase in stillborn pups, a decrease in pup weight, and an increase in pup deaths during the first 7 days postpartum occurred following maternal exposure to 12 mg/kg/day (1.5 times the MRHD on a mg/m2 basis) during gestation or 7.5 mg/kg/day (0. 9 times the MRHD on a mg/m2 basis) during gestation and lactation. Prozac should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus Nonteratogenic Effects Neonates exposed to Prozac and other SSRIs or serotonin and norepinephrine reuptake inhibitors (SNRIs), late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Infants exposed to SSRIs in late pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN)

Key Points:

• Pregnancy Category C: Prozac should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
• Potential Risks: Increased risk of stillborn pups, decreased pup weight, and increased pup deaths in rat reproduction studies.
• Nonteratogenic Effects: Neonates exposed to Prozac may develop complications requiring prolonged hospitalization, respiratory support, and tube feeding.
• PPHN Risk: Infants exposed to SSRIs in late pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN) 3. Prozac is not entirely safe in pregnancy, and its use should be carefully considered, weighing the potential benefits against the potential risks to the fetus.

From the Research

Safety of Prozac in Pregnancy

The safety of Prozac (fluoxetine) in pregnancy is a topic of ongoing research and debate. Several studies have investigated the potential risks and benefits of using Prozac during pregnancy.

• A literature review conducted in 2017 4 found that paroxetine and fluoxetine have the strongest association with negative outcomes, such as significant malformations, persistent pulmonary hypertension of the newborn (PPHN), and poor neonatal adaptation syndrome (PNAS).
• A study published in 2002 5 found that fluoxetine exposure during pregnancy has transient effects on fetal status, including decreases in uterine artery blood flow, fetal PO2, and oxygen saturation.
• Another study published in 2004 6 found no significant differences in obstetrical outcome variables between women with exposure to fluoxetine and those without a history of depression.
• A systematic review and meta-analysis published in 2013 7 found that the odds ratio for major malformations associated with maternal fluoxetine use was 1.12 (95% CI 0.98 to 1.28), suggesting that women who are treated with fluoxetine during the first trimester of pregnancy do not appear to have an increased risk of major fetal malformations.
• A more recent study published in 2021 8 found that prenatal stress-induced neurobehavioural abnormalities, HPA-axis functioning, and underlying brain alterations in rat dams and their offspring can be affected by fluoxetine treatment, with dose-dependent effects on the offspring.

Key Findings

• The current evidence suggests that Prozac may have transient effects on fetal status, but the long-term risks and benefits of using Prozac during pregnancy are still unclear.
• The decision to use Prozac during pregnancy should be made on a case-by-case basis, taking into account the individual woman's medical history, the severity of her depression, and the potential risks and benefits of treatment.
• Further research is needed to fully understand the effects of Prozac on fetal development and to inform evidence-based treatment guidelines for pregnant women with depression.