Is venlafaxine (Effexor) safe to use during pregnancy?

From the Guidelines

Venlafaxine should be used during pregnancy only when the potential benefits outweigh the risks, and this decision should be made in consultation with a healthcare provider. The medication is classified as Pregnancy Category C, meaning that animal studies have shown adverse effects on the fetus, but there are no adequate well-controlled studies in humans. Some research suggests a small increased risk of complications such as preterm birth, low birth weight, and neonatal adaptation syndrome (including irritability, feeding difficulties, and respiratory distress) in newborns exposed to venlafaxine during late pregnancy 1. However, untreated depression during pregnancy also carries significant risks for both mother and baby, including poor prenatal care, inadequate nutrition, increased substance use, and postpartum depression.

According to a critical review and recommendations for future research published in the Journal of Child Psychology and Psychiatry and Allied Disciplines in 2019, intrauterine antidepressant exposure does not substantially increase the risk for two concerning neurodevelopmental problems -- ASD and ADHD 1. The review highlights the importance of considering a wide variety of potential consequences for offspring development and providing services to women with depressive and anxiety disorders and their children to reduce the risk of offspring neurodevelopmental problems.

If you're currently taking venlafaxine and become pregnant, don't stop the medication abruptly as this can cause withdrawal symptoms and depression relapse. Instead, work with your healthcare provider to evaluate your specific situation, considering factors such as the severity of your depression, previous response to treatment, and pregnancy stage. For women with severe depression, continuing medication may be the safest option, while those with milder symptoms might consider non-pharmacological approaches like psychotherapy. The American Psychiatric Association and the American College of Obstetricians and Gynecologists recommend that women and their doctors should work together and consider severity of current symptoms, previous mental health history, and patient treatment preferences when making decisions about antidepressant use during pregnancy 1.

Key considerations for the use of venlafaxine during pregnancy include:

• The potential benefits and risks of the medication
• The severity of the mother's depression and previous response to treatment
• The stage of pregnancy
• The potential for non-pharmacological approaches like psychotherapy
• The importance of not stopping the medication abruptly to avoid withdrawal symptoms and depression relapse. It is essential to weigh these factors and make an informed decision in consultation with a healthcare provider to ensure the best possible outcome for both mother and baby.

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 Non-teratogenic Effects 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.

Key Points:

• Venlafaxine is classified as Pregnancy Category C, meaning it should be used during pregnancy only if clearly needed.
• Animal studies have shown some adverse effects on offspring, but no malformations were observed.
• No adequate and well-controlled studies have been conducted in pregnant women.
• Neonates exposed to venlafaxine in the third trimester may experience complications.
• The decision to use venlafaxine during pregnancy should be made after carefully considering the potential risks and benefits 2.

From the Research

Safety of Venlafaxine in Pregnancy

• The use of venlafaxine during pregnancy has been studied in various research papers, with some indicating potential risks and others suggesting its safety in certain contexts 3, 4, 5.
• A study published in 2017 found that serum concentrations of venlafaxine did not change significantly during pregnancy, suggesting that dose adjustments may not be necessary 3.
• However, a meta-review of meta-analyses published in 2023 found that antidepressant drugs, including venlafaxine, may be associated with an increased risk of major congenital malformations, congenital heart defects, preterm birth, and neonatal adaptation symptoms 4.
• Another study published in 2020 found that venlafaxine was associated with an increased risk of selected birth defects, including anencephaly and craniorachischisis, even after partially accounting for underlying conditions 5.

Efficacy and Tolerability of Venlafaxine

• Venlafaxine has been shown to be effective in treating major depression, with a positive dose-response relationship and a rapid onset of action in some studies 6, 7.
• The drug is generally well-tolerated, with common adverse effects including nausea, somnolence, and dry mouth 6, 7.
• Venlafaxine has been compared to other antidepressants, including selective serotonin reuptake inhibitors, and has been found to have similar efficacy and tolerability 6, 7.

Considerations for Use in Pregnancy

• The decision to use venlafaxine during pregnancy should be made on a case-by-case basis, taking into account the potential risks and benefits of treatment 4, 5.
• Pregnant women taking venlafaxine should be closely monitored for any changes in serum concentrations and for potential adverse effects 3.
• Alternative treatments, such as psychotherapy, may be considered for pregnant women with major depression 4.