What Should You Take When Pregnant?

Antidepressants during pregnancy linked to multiple birth and long term complications

/ Author:  / Reviewed by: Robert Carlson, M.D

The small amount of evidence available about medications and pregnancy makes it tough for women to make informed decisions. Fortunately, researchers are learning more all the time.

A recent review of the research literature finds evidence for a number of complications among women taking antidepressants while pregnant.

The complications include early birth, slightly higher rates of miscarriage and pregnancy complications like pre-eclampsia.

They also found evidence of higher risks for babies' long-term development in women who take antidepressants while pregnant.

"Ask your OB/GYN about medications during pregnancy."

One difficulty with a review of literature like this is that it depends on the quality of the studies. Many of these studies contained small numbers of participants, or the information about when women stopped or started antidepressants during pregnancy could affect the results.

Still, overall, the evidence does show risks about taking SSRIs that women should consider. The review was led by Alice Domar, PhD, from Obstetrics and Gynecology at Beth Israel Deaconess Medical Center. Dr. Domar and colleagues reviewed the research literature that exists related to taking certain antidepressants while pregnant.

The researchers looked specifically for studies involving pregnant women with symptoms of depression and/or who were going through infertility issues and were taking selective serotonin reuptake inhibitors (SSRIs). Commonly prescribed SSRIs include citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), paroxetine (Paxil) and sertraline (Zoloft).

One aim of the study was to "challenge the assumption that the risks of SSRIs use are lower than the risks of untreated mild and moderate depression in pregnant women."

Risks of Taking Antidepressants During Pregnancy

Among the conclusions of the research was that women appear to be more likely to give birth to their babies early (before 37 weeks) if they are taking SSRIs during pregnancy.

Not all the findings were significant, and the results varied, but the increased risk was found in more than 30 studies. The largest study, from 2010, found that women were 46 percent more likely to have a preemie while taking SSRIs. Other types of antidepressants made the risk about twice that of a woman not taking the medications.

Another link between SSRI usage and birth complications involves pregnancy-induced hypertension and pre-eclampsia, a condition in which a woman has high blood pressure and protein in her urine.

For example, in one 2009 study of 5,731 women, 19 percent of the women taking SSRIs developed high blood pressure during pregnancy compared to 9 percent of the pregnant women not taking SSRIs. The risk was highest for women who continued taking the SSRIs beyond the first trimester.

Risks to Babies with Antidepressant Exposure

Women who take SSRIs during pregnancy also appear to be more likely to have babies with respiratory distress or whose weight is in the lowest 10th percentile. The studies in this area are more limited, and the results are mixed, the researchers found. But two studies did find lower birth weights among babies born to moms taking antidepressants even after controlling for other factors.

The researchers also found some evidence that miscarriage rates and birth defect rates are higher in women taking antidepressants, but there were only a few studies on this and the amount of the increased risk was not reported in this review.

The drug with the strongest link to birth defects was paroxetine (Paxil), which showed a link to a higher rate of heart defects in babies born to mothers who took paroxetine while pregnant.

In 2005, the pregnancy risk rating of Paxil was changed from a C to a D by GlaxoSmithKline at the request of the U.S. Food and Drug Administration.

A "C" means that evidence is uncertain about a drug's influence on a child if the drug is used during pregnancy. A "D" means a risk has been shown to exist for the unborn baby.

The researchers' work found evidence as well that antidepressants may contribute to health problems in newborns beyond the complications associated with preterm birth or pre-eclampsia.

For example, one study they looked at from 2006 revealed that 30 percent of babies born to women taking SSRIs were diagnosed with Newborn Behavioral Syndrome, marked by constant crying, jitteriness and problems with feeding.

Some evidence also supported a link between SSRI use during pregnancy and a higher risk of autism and/or delayed motor development in babies.

Who Takes Antidepressants While Pregnant?

According to background information in the paper, antidepressants are currently the most commonly prescribed medication in the U.S. for individuals between 18 and 44. The authors cite an estimate that up to 13 percent of women take an antidepressant during some or all of their pregnancy.

Some women become depressed while experiencing infertility problems and may subsequently be prescribed antidepressants. However, the authors found evidence that this could potentially hinder couples' efforts to conceive.

While the review cited some evidence that taking SSRIs might make it harder to become pregnant, the evidence was not strong. One study found no differences in a range of measures related to a woman's ability to become pregnant while she was taking antidepressants.

Cause for Alarm?

A woman should never stop taking medication without consulting her doctor, and some women may need to take antidepressants while pregnant.

Again, the authors reviewed all the research they could find, but there is still a great deal of research that needs to be done. Many of these studies had small numbers of participants, and often there were too few to establish whether results were due to chance to due to the medications.

Some research simply hasn't been published even though the trials have been done. For example, in looking at whether antidepressants even effectively treat depression, the authors found that data published is lopsided. Out of 74 studies registered with the FDA on antidepressants, a third were never published.

Of the 38 studies finding benefits from antidepressants, all but one was published. But only three of the 36 studies with negative or questionable conclusions were published.

The authors also looked at possible effects of untreated depression on pregnancy outcomes since the treatment of the depression would be the primary benefit of taking antidepressants for women, even if they do work. However, they found that the risks of untreated depression were not significant, unlike the risks of taking SSRIs while pregnant.

"For women with just depression, they usually have preterm birth rates about the same as the control [not taking antidepressants and not depressed]," said senior author Adam Urato, MD, of the Division of Maternal Fetal Medicine within the Department of Obstetrics and Gynecology at Tufts University School of Medicine. "It's the women on the antidepressants where we see the higher rates of preterm birth."

Dr. Urato said the data they found was concerning overall.

"I don't want to be overly alarmist but it is a cause for concern," Dr. Urato told dailyRx News. "A lot of what we're trying to do is to inform the public, patients and physicians about what the science is actually showing."

He said SSRIs have only been on the market since 1987, so it has taken 25 years to start seeing effects and accumulating data.

"The studies we reviewed show high rates of complications with antidepressants," Dr. Urato said. "When you're looking at that risk benefit analysis, we don't see that benefit."

Alternatives to Antidepressants

So what's the alternative to antidepressants for women experiencing depression? The authors looked at studies that used a range of other treatments for depression beyond medication.

These treatments included exercise, relaxation training, yoga, acupuncture and nutritional supplements, but the most effective one they found in the studies was cognitive behavioral therapy.

One study from 2008 revealed that 79 percent of women who received cognitive behavioral therapy had fewer depression symptoms, compared to the 50 percent of women taking medication only who had fewer symptoms.

The authors suggest that women with mild or moderate depression might seek alternatives to medication when possible.

"We want to stress that depressive symptoms should be taken seriously and should not go untreated prior to or during pregnancy, but there are other options out there that may be as effective, or more effective than SSRIs without all the attendant risks," Dr. Domar said in a release about the study.

"More broadly, there is little evidence of benefit from the antidepressants prescribed for the majority of women of childbearing age–and there is ample evidence of risk," the authors wrote.

The study was published October 31 in the journal Human Reproduction. The study did not use external funding, and the authors report no conflicts of interest.

Reviewed by: 
Review Date: 
October 29, 2012