Effect of Low and High Doses of Two Selective Serotonin Reuptake Inhibitors on Pregnancy Outcomes and Neonatal Mortality

Selective serotonin reuptake inhibitors (SSRI) are the most common antidepressant used by pregnant women; however, they have been associated with adverse pregnancy outcomes and perinatal morbidity in pregnant women and animal models. We investigated the effects of two SSRI, fluoxetine and sertraline, on pregnancy and neonatal outcomes in mice. Wild-type mice were treated daily with low and high doses of fluoxetine (2 and 20 mg/kg) and sertraline (10 and 20 mg/kg) from the day of detection of a vaginal plug until the end of lactation (21 days postpartum). Pregnancy rate was decreased only in the high dose of fluoxetine group. Maternal weight gain was reduced in the groups receiving the high dose of each drug. Number of pups born was decreased in the high dose of fluoxetine and low and high doses of sertraline while the number of pups weaned was decreased in all SSRI-treated groups corresponding to increased neonatal mortality in all SSRI-treated groups. In conclusion, there was a dose-dependent effect of SSRI on pregnancy and neonatal outcomes in a non-depressed mouse model. However, the distinct placental transfer of each drug suggests that the effects of SSRI on pup mortality may be mediated by SSRI-induced placental insufficiency rather than a direct toxic effect on neonatal development and mortality.

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Selective serotonin reuptake inhibitors use in pregnancy: a risk assessment study using administrative pharmaceutical data

International Journal for Population Data Science ◽

10.23889/ijpds.v4i3.1167 ◽

2019 ◽

Vol 4 (3) ◽

Author(s):

Shaun Purkiss ◽

Tessa Keegel ◽

Hassan Vally ◽

Dennis Wollersheim

Keyword(s):

Pregnant Women ◽

Pregnancy Outcomes ◽

Serotonin Reuptake ◽

Selective Serotonin Reuptake Inhibitors ◽

Adverse Pregnancy Outcomes ◽

Serotonin Reuptake Inhibitors ◽

Selective Serotonin ◽

Published Data ◽

Childbearing Age ◽

Adverse Pregnancy

BackgroundAntidepressant management with Selective Serotonin Reuptake Inhibitors (SSRI) during pregnancy is associated with risks of congenital malformations and adverse pregnancy outcomes. Main AimWe examined the incidence of SSRI use during pregnancy using Australian administrative pharmaceutical data linked to medical service data detailing antenatal consultations to assess pregnancy risk at current levels of treatment. MethodA published data source from the Australian Pharmaceutical and Medical Benefit Schemes was used to identify pregnant women starting new onset treatments with SSRI medications during the provision of antenatal services. A longitudinal profile of SSRI incidence in the pre, peri and post pregnancy periods were constructed to define incident SSRI use. The potential increased burden from adverse pregnancy outcomes was calculated using estimates of risks from the literature. ResultsFrom 2005-2011, 40,778 women were identified to have started de novo SSRI treatments within 10 years of pregnancy (n=172,951). The prenatal monthly incidence of SSRI prescriptions was 25 per 1000 women in 2005 and 7.5/1000 in 2011. During pregnancy, this incidence fell to 7.5 and 4/1000 women in years, and rose above perinatal levels to between 13 and 33/1000 women one year postnatally (X2 p<.001). At these incidence rates, an estimated 2400 women per year receive SSRI’s during pregnancy. In comparison, with non-depressed pregnant women this potentially results in 10 further cardiovascular defects, 94 pre-term births, and 1 still birth annually. ConclusionThis pharmaco-surveillance study has demonstrated continued use of SSRIs in Australian women of childbearing age but diminishing usage during pregnancy. A small number of women continue to be prescribed SSRI during the prenatal period in Australia with risks of adverse pregnancy outcomes.

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