The teratogenic effects of sertraline in mice.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs), which include paroxetine (Paxil), sertraline (Zoloft), fluoxetine (Prozac), citalopram (Celexa), and escitalopram (Lexapro), are the most common antidepressants prescribed to pregnant women. There is considerable debate in the literature regarding the developmental toxicities of SSRIs individually, and as a class.

METHODS: It is considered unethical to perform developmental toxicity studies on pregnant women, but rodent and nonrodent species provide laboratory-controlled experimental models to examine the toxicity of SSRI exposure during pregnancy. The Embryo-Fetal Developmental Toxicity Study was conducted with sertraline in mice, Crl:CD1 (lCR), during the period of organogenesis.

RESULTS: Increased resorption rates, lower fetal weight, and increased percentage of fetuses with visceral and skeletal abnormalities were found in the intermediate and high sertraline dose groups. In addition to incomplete ossification of treated animals, eleven sertraline exposed fetuses, two in group 2 (5 mg/kg), five in group 3 (25 mg/kg), and four in group 4 (60 mg/kg), had cleft palate (CP). This malformation was not observed in any controls. Only the highest dose of sertraline was found to be maternally toxic, as evidenced by significantly lower weight gain during pregnancy.

CONCLUSION: These data indicate that in utero exposure to sertraline at 25 and 60 mg/kg was embryotoxic, teratogenic, and fetotoxic in mice. The incidence of CP observed in groups 3 and 4 (2.99% and 2.5%, respectively) were higher than the maximum range value noted in historical controls and indicate sertraline is a teratogen in ICR mice.