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Understanding the Impact of Prenatal Fluoxetine Exposure

October 29, 2024 Neuroscience Depression

During pregnancy, the majority of women report psychological stress, with 7% of women developing major depression (Andersson et al., 2003; Gorman et al., 2004), and an additional 7% developing minor depression (Fournier et al., 2010). Prenatal (during pregnancy) depression is linked to various complications in the offspring. These include but are not limited to delayed development in 18-month-old children, increased anxiety in 6 9-year-old children, and a 4.7-fold increased risk of depression for 16-year-olds exposed to prenatal depression (Davis & Sandman, 2012; Deave et al., 2008; Pawlby et al., 2009).

Combining these complications in offspring with the psychological stress experienced by mothers with depression, antidepressant treatment is sometimes unavoidable. There has been an ongoing debate about which antidepressants are most appropriate. For instance, Kirsch et al. (2008) suggest antidepressants only outperform placebo “at the upper end of very severe depression”. Currently, selective serotonin reuptake inhibitors (SSRIs)– specifically fluoxetine (FLX)– are the primary pharmacological treatment for depression, primarily due to their decreased side effect profile (Cascade et al., 2009).

However, SSRIs can cross the placenta, impacting the offspring (Laine et al., 2003). Several effects of SSRI exposure on offspring have been reported; especially an increase in behavioral problems (Hanley et al., 2015; Rai et al., 2013). When the serotonergic neurons adapt because of SSRI exposure, complications seem to arise, most likely because serotonin plays numerous roles in developmental events. For example, Olivier et al. (2011) showed that prenatal fluoxetine exposure significantly increased anxiety in three behavioral tests. Unfortunately, the underlying mechanisms remain elusive.

In humans it is difficult, if not impossible, to study the effects of fluoxetine alone in the offspring, simply because we do not treat healthy women with antidepressants. It is therefore difficult to disentangle the effects of maternal depression and the effects of fluoxetine during pregnancy. Currently, animal models are used to study the effects of fluoxetine in the offspring.

As mentioned, managing maternal depression with antidepressants is sometimes unavoidable. Future studies should explore how genetic and pharmacological interventions can be used to develop safer treatment options that manage maternal depression and do not compromise offspring development. In this regard, much more research needs to be done.

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References

Andersson, L., Sundström-Poromaa, I., Bixo, M., Wulff, M., Bondestam, K., & Åström, M. (2003). Point prevalence of psychiatric disorders during the second trimester of pregnancy: A population-based study. American Journal of Obstetrics and Gynecology, 189(1), 148–154. https://doi.org/10.1067/mob.2003.336​

Cascade, E., Kalali, A., & Kennedy, S. H. (2009). Real-world data on SSRI antidepressant side effects. Psychiatry, 6(2).

Davis, E. P., & Sandman, C. A. (2012). Prenatal psychobiological predictors of anxiety risk in preadolescent children. Psychoneuroendocrinology, 37(8), 1224–1233. https://doi.org/10.1016/j.psyneuen.2011.12.016​

Deave, T., Heron, J., Evans, J., & Emond, A. (2008). The impact of maternal depression in pregnancy on early child development. BJOG, 115(8), 1043–1051. https://doi.org/10.1111/j.1471-0528.2008.01752.x​

Fournier, J. C., DeRubeis, R. J., Hollon, S. D., Dimidjian, S., Amsterdam, J. D., Shelton, R. C., & Fawcett, J. (2010). Antidepressant drug effects and depression severity: A patient-level meta-analysis. JAMA, 303(1), 47–53. https://doi.org/10.1001/jama.2009.1943​

Gorman, L. L., O’Hara, M. W., Figueiredo, B., Hayes, S., Jacquemain, F., Kammerer, M. H., et al. (2004). Adaptation of the structured clinical interview for DSM-IV disorders for assessing depression in women during pregnancy and postpartum across countries and cultures. British Journal of Psychiatry, 184(S46), s17–s23. https://doi.org/10.1192/bjp.184.46.s17​

Hanley, G., Brain, U., & Oberlander, T. (2015). Prenatal exposure to serotonin reuptake inhibitor antidepressants and childhood behavior. Pediatric Research, 78, 174–180. https://doi.org/10.1038/pr.2015.77​

Kirsch, I., Deacon, B. J., Huedo-Medina, T. B., Scoboria, A., Moore, T. J., & Johnson, B. T. (2008). Initial severity and antidepressant benefits: A meta-analysis of data submitted to the food and drug administration. PLoS Medicine, 5(2). https://doi.org/10.1371/journal.pmed.0050045​

Laine, K., Heikkinen, T., Ekblad, U., & Kero, P. (2003). Effects of exposure to selective serotonin reuptake inhibitors during pregnancy on serotonergic symptoms in newborns and cord blood monoamine and prolactin concentrations. Archives of General Psychiatry, 60(7), 720–726. https://doi.org/10.1001/archpsyc.60.7.720​

Olivier, J. D. A., Vallès, A., & van Heesch, F. (2011). Fluoxetine administration to pregnant rats increases anxiety-related behavior in the offspring. Psychopharmacology, 217, 419–432. https://doi.org/10.1007/s00213-011-2299​

Pawlby, S., Hay, D. F., Sharp, D., Waters, C. S., & O’Keane, V. (2009). Antenatal depression predicts depression in adolescent offspring: Prospective longitudinal community-based study. Journal of Affective Disorders, 113(3), 236–243. https://doi.org/10.1016/j.jad.2008.05.018​

Rai, D., Lee, B. K., Dalman, C., Golding, J., Lewis, G., & Magnusson, C. (2013). Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: Population-based case-control study. BMJ. https://doi.org/10.1136/bmj.f2059​-z