The effects of gestational exposure to sertraline and citalopram on maternal and neonatal parameters in the rat

N. A. DeSanctis, J. P. Kelly. Pharmacology and Therapeutics, National University of Ireland, Galway, Ireland.

Introduction: SSRI antidepressants are the most commonly prescribed psychotropic drug in pregnancy¹. SSRIs cross the placental barrier, and clinical gestational exposure is associated with lower birth weights, smaller size in relation to gestational age, reduced gestational length and preterm birth². Previous studies conducted in our laboratory have indicated a decrease in pup bodyweight and higher mortality rates for litters exposed to the SSRIs fluoxetine and paroxetine using a model recently developed in our laboratory³. The present study examined the effects of the other two clinically used SSRIs, namely sertraline and citalopram, during pregnancy in rats to complete the evaluation profile of the four commonly prescribed SSRIs.

Methods: Female Sprague-Dawley rats (approx. 4 months old) were mated and single housed. From gestational day (GD) 7 until littering, mothers received either vehicle, 2.5, 5 or 10 mg/kg sertraline or citalopram via oral gavage, and their bodyweight, food and water consumption were measured, and pup characteristics such as litter size, sex ratio and mortality were monitored following littering. Data were analysed using ANOVA, followed where appropriate by post hoc SNK test. Pup mortality data were analysed using a Chi-Squared test; p<0.05 was deemed statistically significant.

Results: During gestation, only the highest dose of sertraline produced a significant reduction in maternal weight gain whilst 2.5 mg/kg citalopram actually significantly increased weight gain; there were no effects of either drug on maternal food and water intake. There were no differences in litter size and sex ratio of offspring at birth. However, there was a significant increase in mortality within the first week following littering in all dose groups, except for the 5 mg/kg sertraline dose.

Conclusions: Overall, the data demonstrate that at pharmacological doses, both sertraline and citalopram have profound effects on neonatal mortality in the rat. This study produced novel findings as these drugs have not been examined using this approach. These findings are similar to those that we have previously observed in this model using fluoxetine and paroxetine, although to a lesser extent and at higher dosage levels. Such findings in an animal model could have important implications for clinical use of SSRI antidepressants during pregnancy.

References:

1. Alwan S. et al. (2016). CNS Drugs. 30: 499-515.

2. Bourke C.H. et al. (2014). Pharm Rev. 66: 435-465.

3. McDonnell-Dowling K. et al. (2014). Int J Dev Neurosci 35: 42-51

Acknowledgement: This work was supported by a College of Science, NUI Galway postgraduate fellowship.