Studying The Studies — Antidepressants and Pregnancy

Heidi Flagg, MD, obstetrician & EMC medical advisory board member, discusses new study from Columbia University and approaches for treating mothers with depression and anxiety.

A new study from Columbia University’s Mailman School of Public Health analyzed data from almost 850,000 births in Finland between 1996 and 2010 and determined there are upsides and downsides to using antidepressants during pregnancy.

EMC: Dr. Flagg, this study looked at SSRIs, the most commonly used antidepressants for treating depression and anxiety during pregnancy. How did researchers conduct this study?

Dr. Flagg: The gold standard for studying any medication is the randomized, double blind, control study. Patients don’t know if they’re getting a medication or placebo. You simply cannot do this type of study with pregnancy. It isn’t ethical. Let us use alcohol as an example. We cannot gather a group of pregnant women and suggest that ‘you ladies drink a bottle of wine, you all drink a 6-pack of beer and this group should drink water, then let’s see whose kid comes out better.’ This means with pregnancy we’re limited to observational retrospective studies. In this study, researchers looked back at the outcomes from three groups. One group of mothers was diagnosed with a psychiatric disorder and took antidepressants. Another group was diagnosed but was un-medicated. A third group had no diagnosis and no medication.

EMC: What did they find out?

Dr. Flagg: There were quite a few benefits to antidepressant use in addition to mothers being better able to manage their symptoms. The preterm birth rate for mothers on medication was 16% lower. The severely preterm birth rate [24–28 weeks] was 50% lower than the un-medicated mothers with depression. It also appears that antidepressants may have contributed to fewer C-sections. The depressed women who didn’t use SSRIs had a 26.5% C-section rate versus 17% in the group with no depression.

EMC: What’s the link between un-medicated depression/anxiety and C-sections?

Dr. Flagg: Many physical and mental factors have to be optimized for the body to do what it needs to do during labor. The presence or absence of stress plays a major role in the progress of labor. Patients with anxiety and depression have higher levels of stress. There are also many co-morbidities [the presence of more than one illness at a time] associated with depression such as suicidal ideations, nutritional deficiencies, substance abuse and self-medications that may not be recorded. All of these factors can a have a toppling effect on women and very likely interfere with labor progress, thus increasing the risk for C-section.

EMC: The study also addresses potential drawbacks to taking antidepressants.

Dr. Flagg: Right. Some babies had longer NICU stays and respiratory issues. We’re always concerned about medications used in pregnancy increasing risks for birth defects, miscarriage, preterm birth, low birth weight and post-delivery neonatal adaptation problems [babies who have difficulty adapting to life outside the uterus] that may lead to more NICU admissions. This study mentions a 15–30% increase in NICU admissions for poor neonatal adaptation when mothers took SSRIs in late pregnancy. Most of these “withdrawal” symptoms in the newborn are transient. However, this study mentions a six-fold increase in persistent newborn pulmonary hypertension (PPH) cases. This is when explaining to a patient the difference between relative risk and absolute risk is very important. When you delve into the data in this instance, we see a baseline of 1–2 babies in a 1000 with PPH increase to 3–12 in a 1000 with mothers on SSRIs. In absolute numbers, the risk sounds less ominous. It is important that patients understand these numbers and make an informed decision about whether to take medication.

EMC: Many women struggle with the decision to take any medication during pregnancy. How do you address their fears?

Dr. Flagg: In cases of anxiety and depression, I talk them right out of any guilt they might feel. Life’s too short for that. I have frank discussions about the real risks and numbers. The news will report increased risks that sound really frightening, but are actually far less ominous. Medical providers have to dive into the details and talk in real life terms so patients can make decisions based on real risks and benefits and their own circumstances and needs. We have data that supports SSRI-use during pregnancy and generally speaking risks are relatively low.

EMC: Diabetic or asthmatic mothers don’t feel guilty about using their medications yet with anxiety and depression, women feel so much fear.

Dr. Flagg: Mental illness is still taboo and studies aren’t always clear-cut. It’s important to look at confounders — things that interfere with research results. With SSRI research, depression itself can cause the same problems researchers might attribute to antidepressants. We also have to consider the severity of the patient’s depression. Severe depression is more likely to be treated with medication and the effect that’s blamed on SSRIs might actually be caused by the severity of depression. Plus, women on SSRIs may have other psychiatric illnesses and be on other medications. Finally, there’s surveillance bias. Women on medication are often followed more closely than women who aren’t. A physician may uncover something they attribute to antidepressants that may or may not be relevant. For example, ventral-septal defect (VSD), a newborn cardiac anomaly, was linked to Paxil use, an SSRI. Incidentally most of these VSDs heal within a year and aren’t clinically significant. The abnormality may have been there despite the medication. Researchers uncover findings simply because they are following patients more closely. In another study, researchers reported an increased incidence of miscarriage with SSRI use, but they saw the same increase with patients who stopped taking SSRIs months before they became pregnant. In this case, the depression itself may have caused the increase in miscarriage. Surveillance bias can muddy the waters.

EMC: We’re doing a better job identifying anxiety and depression during pregnancy these days but is that because we have more tools like antidepressants for addressing it or are we actually seeing more cases of it?

Dr. Flagg: I think it’s likely both. It has always been hard to be a woman but now we’re faced with so many more challenges — managing careers, being a good partner and motherhood — it’s a lot.

EMC: What about patients who decide not to use antidepressants?

Dr. Flagg: I stress the importance of exercise. Head-to-head studies show that exercise and SSRIs have similar positive results. For pregnant women with depression, exercise is even more important and some patients find it can even help them wean off their medications. Of course, that’s not always the case. If their depression is severe, you have to treat it more aggressively.

EMC: What about other non-medication treatments?

Dr. Flagg: I call it the “organic” approach. This would include counseling, exercise and other non-medicinal techniques. You have to individualize treatment to suit the person in front of you. In my population, patients are very motivated to try this and often report back that it works for them. Sometimes, though, you just have to go with medication. When we decide that’s the best approach, I support them to try and let go of their fears. In the end, depression is worse for a mother and her baby than medication is.