Department of Pediatrics, Dell Pediatric Research Institute, Dell Medical School, University of Texas at Austin, Austin, Texas.
Center for Precision Environmental Health, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.
Birth Defects Res. 2020 Aug;112(13):1014-1024. doi: 10.1002/bdr2.1660. Epub 2020 Feb 19.
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.
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.
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.
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.
选择性 5-羟色胺再摄取抑制剂（SSRIs），包括帕罗西汀（Paxil）、舍曲林（Zoloft）、氟西汀（Prozac）、西酞普兰（Celexa）和艾司西酞普兰（Lexapro），是最常用于治疗孕妇的抗抑郁药。关于 SSRIs 个体的发育毒性以及作为一类药物的发育毒性，文献中存在相当大的争议。
对孕妇进行发育毒性研究被认为是不道德的，但啮齿动物和非啮齿动物提供了实验室控制的实验模型，以检查 SSRI 暴露在怀孕期间的毒性。在妊娠器官发生期间，在 Crl:CD1（ICR）小鼠中进行了舍曲林的胚胎-胎儿发育毒性研究。
在中、高舍曲林剂量组中，发现吸收率增加、胎儿体重降低以及胎儿内脏和骨骼畸形的百分比增加。除了处理动物的不完全骨化外，11 只舍曲林暴露的胎儿，2 只在第 2 组（5mg/kg），5 只在第 3 组（25mg/kg），4 只在第 4 组（60mg/kg）中，有腭裂（CP）。对照组中没有观察到这种畸形。只有最高剂量的舍曲林被发现具有母体毒性，这表现为妊娠期间体重增加显著降低。
这些数据表明，在怀孕的 ICR 小鼠中，暴露于 25 和 60mg/kg 的舍曲林会导致胚胎毒性、致畸性和胎儿毒性。在第 3 组和第 4 组（分别为 2.99%和 2.5%）中观察到的 CP 发生率高于历史对照组中记录的最大值，表明舍曲林在 ICR 小鼠中是一种致畸物。
