Antidepressant
PREGNANCY RECOMMENDATION: Human Data Suggest Risk in 3rd Trimester
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
No reports describing the use of vilazodone, a selective serotonin reuptake inhibitor (SSRI), in human pregnancy have been located. Although the animal data suggest low risk, SSRI antidepressants have been associated with developmental toxicities, including spontaneous abortions, low birth weight, preterm delivery, neonatal serotonin syndrome, neonatal behavioral syndrome (withdrawal), possible sustained abnormal neurobehavior beyond the neonatal period, respiratory distress, and persistent pulmonary hypertension of the newborn (PPHN). The risk:benefit ratio for using any SSRI in pregnancy must be determined on a case-by-case basis.
FETAL RISK SUMMARY
In addition to its action as an SSRI antidepressant, vilazodone hydrochloride also is a partial agonist at serotonergic 5-HT1A receptors. It is indicated for the treatment of major depressive disorder. Vilazodone is in the same class of SSRIs as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. Vilazodone is extensively metabolized to inactive metabolites. Plasma protein binding is about 96%–99% and the terminal half-life is about 25 hours (1).
Reproduction studies have been conducted in rats and rabbits. No teratogenic effects were observed in either species at oral doses that were 48 and 17 times, respectively, the maximum recommended human dose of 40 mg based on BSA (MRHD). However, at these doses, fetal body weight gain was reduced and skeletal ossification was delayed in both rats and rabbits. These effects were not observed at doses up to 10 and 4 times, respectively, the MRHD. Some maternal toxicity (not otherwise specified) was noted in rats given a dose that was 30 times the MRHD during organogenesis and throughout pregnancy and lactation. Fetal effects observed at this dose included decreased number of live pups and increased early postnatal pup mortality. Among surviving pups there was decreased body weight, delayed maturation, and decreased fertility in adulthood. These effects were not observed at dose 6 times MRHD (1).
Two-year carcinogenicity studies have been conducted in mice and rats. In mice, dose-related hepatocellular carcinomas were observed in males and malignant mammary gland tumors in females. Elevated levels of prolactin also were observed and are known to cause mammary tumors in rodents. No carcinogenic effects were seen in male and female rats. Vilazodone was not mutagenic in various assays. It was clastogenic in some assays but not in others. Dose-related impairment of male fertility was observed in rats but there was no effect on female fertility (1).
It is not known if vilazodone crosses the human placenta. The molecular weight (about 478) and long terminal half-life suggest that the drug will cross to the embryo–fetus. However, the high plasma protein binding may limit the amount of transfer.
BREASTFEEDING SUMMARY
No reports describing the use of vilazodone during human lactation have been located. The molecular weight (about 478) and long terminal half-life (about 25 hours) suggest that the drug will be excreted into breast milk. Although the high plasma protein binding (96%–99%) may limit the amount excreted, vilazodone is a weak base and because the pH of milk is usually lower than that of plasma, milk concentrations may be higher than plasma levels due to “ion trapping.”
The effect of exposure to the drug in milk by a nursing infant is unknown. However, excessive somnolence, decreased feeding, and weight loss have been observed in infants exposed to another SSRI (see Citalopram). Thus, nursing infants should be closely monitored for evidence of toxicity. The American Academy of Pediatrics classifies other SSRI antidepressants as drugs for which the effect on nursing infants is unknown but may be of concern (e.g., see Fluoxetine).
A 2010 study using human and animal models found that drugs that disturb serotonin balance such as SSRIs and serotonin norepinephrine reuptake inhibitors (SNRIs) can impair lactation (2). The authors concluded that mothers taking these drugs may need additional support to achieve breastfeeding goals.
References
1.Product information. Viibryd. Forest Pharmaceuticals, 2011.
2.Marshall AM, Nommsen-Rivers LA, Hernandez LI, Dewey KG, Chantry CJ, Gregerson KA, Horseman ND. Serotonin transport and metabolism in the mammary gland modulates secretory activation and involution. J Clin Endocrin Metab 2010;95:837–46.