SSRI Use in Pregnancy: Safe or Not?

Use of selective serotonin reuptake inhibitor (SSRI) antidepressants during pregnancy appears to be reasonably safe for the baby and mother. There are a few ways in which a foetus could be affected by drugs it is exposed to in the womb, and the spectrum is certainly not fully studied at this stage.

SSRIs remain one of the most studied drugs during pregnancy. Some of the areas studied include anatomical abnormalities/birth defects, and the risk of autism.

SSRIs and anatomical abnormalities/birth defects

‘Pretty safe’ means there do appear to be some very mildly increased risks of birth defects overall, however that the benefits of mental health in the pregnancy outweigh the risks. Studies reveal some increased risks of specific malformations.

Key takehomes:

Overall, SSRI use during pregnancy has not been associated with specific risks to the foetus, but some risks may be slightly increased with SSRI use
Discontinuation of antidepressants that manage mental states/illness during pregnancy is associated in relapse of depression with negative consequences

What the research tells us

Antidepressants are one of the most studied drugs in pregnancy, so there is a lot of data to draw on. The overall anatomical abnormality risk is about three per cent for the general population, with most of these being heart-related.

It’s also worth noting that many of these abnormalities are self-correcting in the months after a baby is born.

A study in Finland (Malm et al) of over 600,000 mother-child pairs found that women who bought selective serotonin reuptake inhibitor (SSRI) antidepressants for the first time were:

Less likely to be married
More likely to smoke
More likely to have chronic diseases
More likely to use non-SSRI psychotropic drugs
More likely to use non-psychotropic drugs
No significant increase in risk for all major malformations
Paroxetine increased the risk of right ventricular outflow tract defects (RVOT) five-fold
Fluoxetine doubled the risk of ventricular septal defects (VSD)
Citalopram increased the risk of neural tract defects 2.5-fold
The risk of foetal alcohol spectrum disorders increased 10-fold in SSRI exposed cases

Another large study (Huybrechts, et al. 2014) of Medicaid populations revealed that there was an increased risk of major cardiac malformations (MCMs), which includes ventricular flow obstruction and ventricular septal defects in infants exposed to SSRIs during the first trimester.

When we look at data that has not been adjusted, there is an increased risk of overall cardiac defects with any antidepressants and with SSRIs as a group.

When adjusted, however, the data reveals no ‘statistically significant’ risk of any cardiac malformation with first trimester exposure to any antidepressants including SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), and bupropion.

Should I keep taking antidepressants during pregnancy?

This is a conversation between you and your doctor, and will depend on many factors. The prevailing wisdom is that SSRIs are safe to use during pregnancy, and the risk of malformations in the baby is low compared with those not on SSRIs.

Staying healthy and happy during pregnancy is a challenge for anyone, but if you are depressed, this may be more important for people suffering from depression.

Remaining on medication to manage depression may outweigh the risks to the foetus. If you have time before getting pregnant, discuss your options with your doctor for clarity.

SSRIs and the risk of autism

Some studies have suggested an increased risk of a child being born with autistic spectrum disorders (ASD) after prenatal exposure to antidepressants.

When the research data is smushed and confounding factors are accounted for, the risk is reduced or often nonexistent. Treating parents who are suffering psychiatrically is an important element that needs careful consideration and monitoring.

Pregnancy, childbirth and parenting are all intense challenges, and if someone is already having trouble facing challenges, treatment becomes an important part of life.

The overall view by medicine is that the person carrying and caring for the child is just as important to consider as the foetus, and a balancing act is key.

The association between antidepressant use during pregnancy and ASD

At first there were three case-controlled studies published regarding the use of SSRIs and pregnancy, and a link with autism. All three of these case studies suggested a possible association between antidepressants and ASD.

First case-controlled study findings

The Kaiser study found an association only with SSRIs
The Swedish study found an association with SSRIs and other antidepressants
The Californian study found an association with SSRIs for ASD and a possible developmental delay in boys
None of these studies could explain the huge rise in ASD since the 1980s, with all having problems regarding confounding by indication

The first large Danish study

Then came a Danish study of over 500,000 children and about 9,000 of these children having had prenatal exposure to SSRIs. The risk of autism in these children, compared to those without SSRIs, was two per cent. The non-SSRI-treated offspring had a 1.5 per cent chance of having ASD.

However, if the data was restricted to children born to a person with prenatal affective disorders (depression, bipolar, anxiety), there was no statistically significant risk in ASD with prenatal SSR exposure.

When comparing siblings with and without ASD, prenatal SSRI exposure was not a significant contributor to ASD risk. The researchers concluded that there was no significant association between prenatal SSRI exposure and autism spectrum disorders in offspring.

The second large Danish study

A large study on Danish families found that SSRI exposure before pregnancy, as opposed to during pregnancy, was statistically significantly with an increased risk for ASD.

The researchers concluded that this increased risk was due to other factors such as depression in the parent, rather than by an effect of the SSRIs.

Issues for studies on SSRIs in pregnancy and its relationship with ASD

There are no randomised controlled studies of antidepressants in pregnancy
There are a lot of unknowns – genes, behaviour, environmental
Many studies cover the same population databases so are not as big as they seem
Many studies covering the same populations don’t always arrive at the same conclusions
Some of these studies came to conclusions that were unexplainable by their own data or findings

A review of multiple meta-analyses found:

Exposure to antidepressants in pregnancy is associated with a significantly increased risk of ASD
These findings diminished in magnitude and significance when adjusted for confounding variables
Antidepressants are associated with an increased risk of ASD even in preconception periods when the drugs could not have possibly affected the foetus
This leads the suggestion that maternal mental illness is a much greater driver of ASD in offspring than antidepressants

What to do if you are concerned about risks of antidepressants during pregnancy

The best thing you can do is speak to your doctor about your concerns. If you are able to digest scientific research, check out the papers in the references section and do your own research online.

The conclusions appear to be (at this time) that SSRIs do not increase a child’s risk of ASD. It appears to be more more likely that other psychiatric factors come into play that existed prior to pregnancy.

References – SSRIs and birth defects

Malm, H., Artama, M., Gissler, M., & Ritvanen, A. (2011). Selective serotonin reuptake inhibitors and risk for major congenital anomalies. Obstetrics & gynecology, 118(1), 111-120.
Huybrechts, K. F., Palmsten, K., Avorn, J., Cohen, L. S., Holmes, L. B., Franklin, J. M., … & Hernández-Díaz, S. (2014). Antidepressant use in pregnancy and the risk of cardiac defects. New England Journal of Medicine, 370(25), 2397-2407.
Alwan, S., Reefhuis, J., Rasmussen, S. A., Olney, R. S., & Friedman, J. M. (2007). Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. New England Journal of Medicine, 356(26), 2684-2692.
Louik, C., Lin, A. E., Werler, M. M., Hernández-Díaz, S., & Mitchell, A. A. (2007). First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. New England Journal of Medicine, 356(26), 2675-2683.Greene, M. F. (2007). Teratogenicity of SSRIs—serious concern or much ado about little?.
Wisner, K. L., Sit, D. K., Hanusa, B. H., Moses-Kolko, E. L., Bogen, D. L., Hunker, D. F., … & Singer, L. T. (2009). Major depression and antidepressant treatment: impact on pregnancy and neonatal outcomes. Focus, 7(3), 374-384.
Stewart, D. E. (2012). Clinical Practice: Depression During Pregnancy. Obstetric Anesthesia Digest, 32(4), 208-209.

References – SSRIs and ASD

Croen, L. A., Grether, J. K., Yoshida, C. K., Odouli, R., & Hendrick, V. (2011). Antidepressant use during pregnancy and childhood autism spectrum disorders. Archives of general psychiatry, 68(11), 1104-1112.
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, 346, f2059.
Harrington, R. A., Lee, L. C., Crum, R. M., Zimmerman, A. W., & Hertz-Picciotto, I. (2014). Prenatal SSRI use and offspring with autism spectrum disorder or developmental delay. Pediatrics, peds-2013.
Sørensen, M. J., Grønborg, T. K., Christensen, J., Parner, E. T., Vestergaard, M., Schendel, D., & Pedersen, L. H. (2013). Antidepressant exposure in pregnancy and risk of autism spectrum disorders. Clinical epidemiology, 5, 449.
Hviid, A., Melbye, M., & Pasternak, B. (2013). Use of selective serotonin reuptake inhibitors during pregnancy and risk of autism. New England Journal of Medicine, 369(25), 2406-2415.
Brown, H. K., Hussain-Shamsy, N., Lunsky, Y., Dennis, C. E., & Vigod, S. N. (2017). The association between antenatal exposure to selective serotonin reuptake inhibitors and autism: a systematic review and meta-analysis.
Sujan, A. C., Rickert, M. E., Öberg, A. S., Quinn, P. D., Hernández-Díaz, S., Almqvist, C., … & D’Onofrio, B. M. (2017). Associations of maternal antidepressant use during the first trimester of pregnancy with preterm birth, small for gestational age, autism spectrum disorder, and attention-deficit/hyperactivity disorder in offspring. Jama, 317(15), 1553-1562.
Andrade, C. (2017). Antidepressant Exposure During Pregnancy and Risk of Autism in the Offspring, 1: Meta-Review of Meta-Analyses.