What are the implications of using Venlafaxine (Effexor) in pregnancy?

From the Guidelines

Venlafaxine can be used during pregnancy when the benefits outweigh the risks, but it should be prescribed with caution, as the most recent and highest quality study suggests that intrauterine antidepressant exposure does not substantially increase the risk for neurodevelopmental problems, such as ASD and ADHD 1.

Key Considerations

• For pregnant women with moderate to severe depression or anxiety disorders, venlafaxine at the lowest effective dose (typically starting at 37.5mg daily, increasing as needed) may be appropriate.
• The medication should not be abruptly discontinued if a woman becomes pregnant while taking it, as untreated depression poses significant risks to both mother and baby.
• Some studies suggest a small increased risk of postpartum hemorrhage and a potential slight increase in the risk of persistent pulmonary hypertension of the newborn with third-trimester exposure.
• Neonatal adaptation syndrome (including irritability, feeding difficulties, and respiratory distress) may occur in approximately 30% of infants exposed to venlafaxine late in pregnancy, but symptoms are usually mild and self-limiting.

Monitoring and Consultation

• When possible, psychiatric consultation should be obtained to help weigh individual risks and benefits.
• Close monitoring during pregnancy is essential, with potential dose adjustments needed due to pregnancy-related pharmacokinetic changes.
• Breastfeeding while taking venlafaxine is generally considered acceptable, as minimal amounts pass into breast milk.

Decision-Making

• The decision to use venlafaxine during pregnancy should be made on a case-by-case basis, taking into account the severity of the mother's symptoms, her medical history, and her preferences 1.
• The American Psychiatric Association and the American College of Obstetricians and Gynecologists recommend that women and their doctors work together to consider the severity of current symptoms, previous mental health history, and patient treatment preferences when making decisions about antidepressant use during pregnancy 1.

From the FDA Drug Label

Venlafaxine did not cause malformations in offspring of rats or rabbits given doses up to 11 times (rat) or 12 times (rabbit) the maximum recommended human daily dose on a mg/kg basis, or 2. 5 times (rat) and 4 times (rabbit) the human daily dose on a mg/m2 basis. However, in rats, there was a decrease in pup weight, an increase in stillborn pups, and an increase in pup deaths during the first 5 days of lactation, when dosing began during pregnancy and continued until weaning. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed Neonates exposed to venlafaxine HCl, other SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors), or SSRIs (Selective Serotonin Reuptake Inhibitors), late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Newborns whose mothers take venlafaxine HCl in the third trimester may have problems right after birth including: • problems feeding and breathing • seizures • shaking, jitteriness or constant crying

Venlafaxine use in pregnancy should be approached with caution. The drug label indicates that:

• Animal studies have shown no malformations, but there were some adverse effects on pup weight and survival.
• There are no adequate and well-controlled studies in pregnant women.
• Neonates exposed to venlafaxine in the third trimester may experience complications, including respiratory distress, seizures, and feeding problems.
• The decision to use venlafaxine during pregnancy should be made only if clearly needed, weighing the potential benefits against the potential risks 2.
• It is also mentioned that if you are pregnant or plan to become pregnant, you should talk to your healthcare provider about the benefits and risks of treating depression during pregnancy 3.

From the Research

Venlafaxine Use in Pregnancy

• Venlafaxine is a serotonin noradrenaline reuptake inhibitor used to treat major depressive episodes and anxiety disorders 4.
• The use of venlafaxine during pregnancy may require dose adjustments due to changes in drug disposition 5, 6.

Dose Adjustments

• A study found that serum concentrations of venlafaxine did not change significantly during pregnancy, suggesting that dose adjustments may not be necessary 5.
• However, another study using a pharmacokinetic modelling approach found that venlafaxine trough plasma concentrations decreased significantly throughout gestation, requiring dose adjustments for extensive metabolizer (EM) and ultra-rapid metabolizer (UM) phenotypes 6.
• The suggested daily dose for EM is 225 mg in the first trimester, 262.5 mg in the second trimester, and 375 mg in the third trimester, while for UM, a dose of 375 mg daily throughout gestation is suggested 6.

Pregnancy Outcomes

• A prospective observational comparative cohort study found no statistically significant differences in the hazard of spontaneous abortion following gestational venlafaxine use compared to antidepressant unexposed or SSRI exposed pregnancies 4.
• A systematic review of studies found that exposure to venlafaxine in early pregnancy is not associated with an increased risk of major congenital malformations 7.
• However, a case-control study found associations between venlafaxine use and specific birth defects, including anencephaly and craniorachischisis, which persisted after partially accounting for underlying conditions 8.

Birth Defects

• The use of venlafaxine during pregnancy has been associated with an increased risk of certain birth defects, including congenital heart defects and non-cardiac defects 8.
• However, the evidence is limited, and further studies are needed to confirm these findings and to fully understand the risks and benefits of venlafaxine use during pregnancy 7, 8.