Reading Beyond the Headlines: A Closer Look at the Study on Antidepressants During Pregnancy

A recent study regarding the use of antidepressants has been gaining a lot of media attention. The actual study, The risks of selective serotonin reuptake inhibitor use in infertile women: a review of the impact on fertility, pregnancy, neonatal health and beyond (Domar, Moragianni, Ryley & Urato, 2012) has been described by media with a fair amount of fear-based headlines. Safety regarding the use of a specific type of antidepressant medication, selective serotonin reuptake inhibitor (SSRIs), is an important topic of research, as care providers from many fields address the prevalence and negative effects of depression and other mood disorders in pregnancy.

Understandably, pregnant women and their families may be greatly alarmed by these dramatic press releases, and in some cases may consider suddenly discontinuing their medication, without realizing the significant risks that accompany suddenly stopping medication. What do the experts say?

I asked the study's lead researcher, Alice Domar, MD what advice she would offer a pregnant woman who is currently on one of the SSRI medications listed in the study to do, and she kindly offered this response:

"I would never recommend the sudden discontinuation of an SSRI during pregnancy. There are significant side effects associated with the abrupt cessation of antidepressants and we don't know the impact on the developing fetus. The three main points we were trying to make with the paper were: 1) there are risks associated with taking SSRIs during pregnancy, 2) there are no clear benefits, and 3) each patient needs to have a discussion with her physician about her individual risk/benefit ratio. There is a huge difference between a woman who is suicidal, who in all likelihood should remain on medication, versus women with mild or moderate symptoms who would benefit from a different approach, such as cognitive behavioral therapy, or physical exercise, both of which are very effective in the treatment of depressive symptoms." --Alice Domar, MD (personal email communication, 11/2/12)

Another of the study's researchers, Dr. Adam Urato, offered this follow-up:

"Your question is a good one (What would you advise a pregnant woman who is currently on one of the SSRI medications listed in the study to do?) and it is one I deal with several times each week as an Maternal-Fetal Medicine specialist. I agree with Dr. Domar's comments. Sudden discontinuation of the SSRIs is not recommended. They should be tapered for those who plan to discontinue them. The patient and their pregnancy health care provider (and their mental health provider) need to be aware of the scientific evidence regarding these drugs. That evidence shows significant risk of pregnancy complications (like miscarriage and preterm birth) and no evidence of benefit for moms and babies. In non-pregnant populations, alternatives like cognitive behavioral therapy and exercise appear to be as effective as the SSRI antidepressants and without the side effects and pregnancy risks." (Personal email communication, 11/2/12)

Reaching out to experts in the field provided roundtable perspective. Christina Chambers, MPH, PhD, California Teratogen Information Specialist (CTIS) and director of the Pregnancy Health Information Line, had these thoughts:

"I agree with the authors' comments. Caution is warranted, treatment makes sense when benefits are clear, and women with less severe illness might consider alternative approaches if they work, abrupt discontinuation without doctor's advice is not a good idea, and care needs to be taken to address the issue of complications for mother and baby of untreated or poorly treated maternal depression. If a woman has questions, she should consult her doctor. She can also call the Organization of Teratology Information Specialists (OTIS) at 866-626-6847 to speak to an expert in this field." (Personal email communication, 11/2/12)

Lucy Puryear, MD, immediate past president of Postpartum Support International (PSI) and Medical Director of The Women's Place: Center for Reproductive Psychiatry offered:

"For women with mild to moderate depression psychotherapy and alternative treatments are absolutely the first choice. But for women with moderate to severe depression that is impairing functioning, antidepressants must be an option. Antidepressants do work in this population and save lives. Our challenge is to continue to look for the safest and most effective treatments for women during this vulnerable period." (Personal email communication, 11/2/12)

PSI's Executive Director Wendy N. Davis, PhD, agreed,

"We are most concerned that women will be unduly frightened by articles that discuss risks of antidepressants but do not discuss positive experiences or research studies that show little statistical relationship between SSRI use and pregnancy outcome. We want to connect women with reliable resources and experts in perinatal psychiatry so they can make thoughtful decisions about treatment options for depression and anxiety during pregnancy."

A word about the science...

One of the pre-eminent researchers in the field, Adrienne Einarson of The Motherisk Program, shared some important criticisms of this study:

Here are my main problems with this publication:

1) It is said to be a review on treatment for infertility patients, however, one-third of the paper is about the lack of efficacy of antidepressants in general.
2) To say there is no evidence for effectiveness in pregnancy is true, but that is simply because there are no RCTs (randomized control studies), not because this has been proven.
3) All of the studies that were picked were ones that found negative effects, with no mention of how marginal the statistical significance really was.
4) The paragraph that is the most concerning is the one starting with "There is compelling evidence that SSRI use prior to and during pregnancy can pose significant risks to the pregnancy and to the short- and long-term health of the baby..." Of course there is compelling evidence when you choose your studies to fit your hypothesis.

This was a biased review, not a systematic one as reviews should be. In fact, there was not a single study referenced in this paper that did not find any harmful effects when there are many that have been published. (Personal email communication, 11/4/12)

When I was pregnant with my daughter, I had a sinus infection. I went to a general practitioner for treatment and shared that I was on an SSRI. You would have thought I told her I was shooting heroine every hour on the hour while tossing back jello shots and chain smoking! If I hadn't had the science from my research treatment team at the UCLA Women's Life Center, I could have easily been scared into stopping my medication. Instead I pulled out a collection of evidence-based research I carried in my purse and left it with her.

Unfortunately, for a woman who is pregnant and has depression, trying to decipher headlines and the seemingly constant stream of warnings might be overwhelming. Not to mention the stigma that accompanies depression and motherhood. Most don't realize that to be that mom means you have to be constantly armed with proof that you are not harming your child. This is where having Adrienne Einarson's insights can help you navigate the science, and advocate for your health and well-being.

Take Home Message:

If you are currently pregnant and taking an SSRI, do not abruptly stop taking your medication until you talk health care provider about risks and benefits for your individual care. If you feel you may be experiencing depression or anxiety and are pregnant, you deserve help with your symptoms. Not getting help has been proven to have negative effects on a developing fetus and increases the risk of pre-term birth, lower birth weight, and postpartum depression. Discuss your symptoms with your care provider immediately. I highly recommend using the resources available at OTIS (866) 626-6847 to address your concerns and questions.

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Walker would like to thank Alice Domar MD; Adam Urato, MD; Christina Chamber, PhD, MPH; Lucy Puryear, MD; Wendy Davis, PhD; and Adrienne Einarson for their contributions.

Reference

Domar, A. D., Moragianni, V. A., Ryley, D.A., & Urato, A.C. (2012). The risks of selective serotonin reuptake inhibitor use in infertile women: a review of the impact on fertility, pregnancy, neonatal health and beyond. Human Reproduction, Vol.0(0) pp. 112 doi:10.1093/humrep/des383

Other Resources:

Department of Health and Human Services: Depression During and After Pregnancy: A Resource for Women, Their Families, & Friends