Is vilazodone (selective serotonin reuptake inhibitor) safe to use during pregnancy in a female patient of childbearing age with a history of depression or anxiety?

Vilazodone Safety During Pregnancy

Vilazodone should be discontinued when pregnancy is recognized due to extremely limited safety data and concerning preclinical evidence of developmental neurotoxicity. 1

Primary Recommendation

Alternative antidepressant agents with established safety profiles are strongly preferred over vilazodone during pregnancy. 2, 1 The American College of Obstetricians and Gynecologists explicitly states that vilazodone should be discontinued upon pregnancy recognition, with alternative agents preferred. 1

Evidence Base and Rationale

Absence of Human Safety Data

• There are no published studies of vilazodone use in human pregnancy. 2
• This represents a critical knowledge gap that prevents any reassurance about safety in pregnant women. 2
• The FDA labeling advises pregnant women to notify their healthcare provider and discusses potential neonatal complications with late pregnancy use, though this is based on class effects rather than vilazodone-specific data. 3

Concerning Preclinical Evidence

Recent animal studies reveal significant developmental concerns:

• Prenatal vilazodone exposure at therapeutic-equivalent doses caused substantial maternal and embryo-fetal toxicity including reduced fetal and placental weights, smaller litter sizes, and decreased maternal weight gain. 4
• Developmental neurotoxicity was documented with decreased fetal brain size and weight, reduced neocortical layer thickness, and disrupted BDNF/Bax-Bcl2/5-HT signaling pathways. 4
• Long-lasting neurobehavioral impairments manifested as increased depressive- and anxiety-like behaviors in offspring of both sexes exposed prenatally. 5
• Neurotransmitter disruption included substantially reduced serotonin, dopamine, and norepinephrine levels in offspring brains. 4, 5

Safer Alternatives for Depression During Pregnancy

When antidepressant treatment is necessary during pregnancy, consider agents with more robust safety data:

• SSRIs with extensive pregnancy data (such as sertraline or fluoxetine) have been studied in thousands of pregnancies with generally reassuring outcomes regarding major malformations. 6
• The magnitude of documented risks with established antidepressants is very low, and treatment should not be stopped if required for daily functioning. 2
• SNRIs like venlafaxine have cumulative data from over 3,000 exposed infants showing no increased risk of major congenital malformations (RR 1.12,95% CI 0.92-1.35). 6

Clinical Decision-Making Framework

If Patient is Currently on Vilazodone and Planning Pregnancy:

• Switch to a better-studied antidepressant before conception with established pregnancy safety data. 1
• Engage in thorough risk-benefit discussion regarding medication choice and lowest effective dose. 2

If Pregnancy is Discovered While on Vilazodone:

• Discontinue vilazodone immediately and transition to an alternative agent with known pregnancy safety. 1
• Do not abruptly discontinue without a transition plan, as discontinuation syndrome can occur. 3
• Monitor closely for return of depressive symptoms during the transition period.

Weighing Untreated Depression Risks:

• Untreated depression carries significant risks including increased spontaneous abortion and preterm birth. 2
• However, this does not justify using vilazodone when safer alternatives with established safety profiles exist. 1

Critical Pitfalls to Avoid

• Do not assume class effects apply to vilazodone - the concerning preclinical neurodevelopmental data are specific to this agent. 4, 5
• Do not continue vilazodone simply because the patient is stable - the lack of human safety data combined with concerning animal studies warrants switching to better-studied alternatives. 1
• Do not wait to see if pregnancy occurs - preconception planning and medication optimization should occur before pregnancy. 2

Breastfeeding Considerations

• It is unknown if vilazodone passes into breast milk. 3
• No published studies exist on vilazodone use during breastfeeding. 2
• The same principle applies - alternative agents with established lactation safety profiles are preferred.