Meta-analysis: Use of SSRIs in Pregnancy Puts Baby at Risk

[Altostrata]

How many studies like this will it take to restrict antidepressant prescription to pregnant women and women who plan to become pregnant?

 

http://www.medpagetoday.com/OBGYN/Pregnancy/35679

 

Use of SSRIs in Pregnancy Puts Baby at Risk

By Cole Petrochko, Staff Writer, MedPage Today

Published: November 01, 2012

 

Action Points

This literature review was conducted to evaluate treatment of depression in pregnant women and to challenge the assumption that the risks of selective serotonin reuptake inhibitor (SSRI) use are lower than the risks of untreated mild and moderate depression during pregnancy.

 

The investigators found that antidepressant use during pregnancy is associated with increased risks of miscarriage, birth defects, preterm birth, newborn behavioral syndrome, persistent pulmonary hypertension of the newborn, and possible longer-term neurobehavioral effects, and there was no evidence of improved pregnancy outcomes with antidepressant use.

 

Pregnant women who took antidepressants were at risk for miscarriage and preterm delivery, and their babies were at risk for a number of developmental and health complications, researchers found.

 

A systematic review of studies looking at the effects of selective serotonin reuptake inhibitors (SSRIs) in pregnant women on infant outcomes showed a significant relationship between SSRI use and preterm birth (OR 1.46, 95% CI 1.31 to 1.63), persistent pulmonary hypertension of the newborn (OR 2.1, 95% CI 1.5 to 3.0), preeclampsia (OR 1.53, 95% CI 1.33 to 1.69), and long-term neurobehavioral effects, according to Alice Domar, PhD, of Beth Israel Deaconess Medical Center in Waltham, Mass., and colleagues.

 

SSRI use in women also was associated with a higher risk of miscarriage, birth defects, newborn behavioral syndrome, neonatal electrocardiograph changes, and fetal growth effects, they wrote online in Human Reproduction.

 

"A standard recommendation for women who report the need for medication to treat symptoms of depression during their pregnancy has been that the benefit of antidepressant use outweighs the risk of depression during the gestational and postpartum period," Domar and colleagues said.

 

Studies Equivocal

 

The researchers reviewed current literature about the efficacy and impact of SSRIs on depression treatment and on fertility and infertility to "challenge the assumption that the risks of SSRIs use are lower than the risks of untreated mild and moderate depression in pregnant women," and to look at the impacts of SSRIs on neonatal health.

 

They noted that, of 74 FDA-registered studies on antidepressants, 38 had positive results, while 36 had negative or questionable results. Of the negative or questionable studies, 22 were unpublished and 11 were published with a positive spin "that conflicted with the FDA's conclusion."

 

"Overall, the preponderance of evidence suggests that antidepressants do not provide clinically meaningful benefit for most patients with mild or moderate depression," they wrote.

 

The authors also noted that SSRI exposure during pregnancy "appears to increase rates of miscarriage," citing a report from the American Psychiatric Association (APA) and the American College of Obstetricians and Gynecologists (ACOG)....

 

Higher Risk of Birth Defects

 

On birth defects, Domar and colleagues wrote that "there has been a consistent 'signal' implicating SSRI use during pregnancy to various congenital anomalies," but that study results have been mixed. They cited a 2005 warning from the FDA, which changed the pregnancy category of paroxetine (Paxil) from category C to D, indicating that the drug demonstrated a risk of cardiac defects in the fetus.

 

....

With regard to premature birth, an "overwhelming majority" of 30 studies looking at preterm birth rates among mothers taking antidepressants versus those who were not showed an association between drug use and preterm birth "across all classes of antidepressants," including SSRIs, serotonin-norepinephrine reuptake inhibitors (OR 1.98, 95% CI 1.49 to 2.63), and tricyclic antidepressants (OR 2.36, 95% CI 1.89 to 2.94).

 

In addition to those risks, "it is now well established that newborns who have been exposed to antidepressants in utero have high rates of what has been called the newborn behavioral syndrome," which includes symptoms of persistent crying, jitteriness, and difficulty feeding, as well as more severe symptoms of seizures and difficulty breathing, the authors wrote.

 

And measures of neonatal electrocardiograph changes showed that infants exposed to SSRIs during pregnancy developed prolonged QT syndrome, with some 10% having "markedly prolonged QT intervals" -- which could lead to a fatal ventricular arrhythmia, they added.

 

Preeclampsia Also More Common

 

In terms of respiratory issues, the largest study of persistent pulmonary hypertension of the newborn -- a condition that causes elevated pulmonary blood pressure that can in turn cause neonatal respiratory distress and hypoxemia -- in infants exposed to antidepressants during pregnancy showed that late pregnancy exposure to SSRIs increased risk of the condition by more than twofold (OR 2.1, 95% CI 1.5 to 3.0).

 

The investigators said that preeclampsia is common in 5% to 10% of pregnancies, but that two studies showed an association between antidepressant use and raised odds of the condition. In one study, early use of antidepressants was tied to 28% greater odds of developing preeclampsia (95% CI 1.19 to 1.37), while late use was tied to 38% greater odds (95% CI 1.25 to 1.53), and early and late use drove up odds by 50% (95% CI 1.33 to 1.69).

 

A second study from Canada showed SSRI use was tied to 53% greater likelihood of pregnancy-induced hypertension (95% CI 1.01 to 2.33), and that paroxetine, in particular, carried 81% greater odds (95% CI 1.02 to 3.23).

 

Birthweight in SSRI-exposed infants "was significantly less than that for depression-only exposed infants," and later exposure to SSRIs during pregnancy was tied to a greater risk of low birthweight. The APA and ACOG published a report in 2009 verifying these findings, the researchers added.

 

Neurobehavioral Effects a Concern

 

Domar and co-authors also noted a number of long-term infant neurobehavioral effects significantly associated with second- or third-trimester exposure to SSRIs in pregnant women, including:

 

Delayed sitting by 15.9 days (95% CI 6.8 to 25.0)

Delayed walking by 28.9 days (95% CI 15.0 to 42.7)

Delayed sitting without support (OR 2.1, 95% CI 1.23 to 3.60)

Inability to occupy self at 19 months (OR 2.1, 95% CI 1.09 to 4.02)

 

The exposure also increased likelihood of developing autism spectrum disorders twofold, particularly with first-trimester use.

 

The authors noted that psychotherapy and physical exercise are associated with significant decreases in depressive symptoms "in the general population," and that healthcare professionals treating depressed women who are or may become pregnant may want to consider non-SSRI alternatives to depression treatment, particularly given recent findings that SSRI use was not much more efficacious than placebo, they wrote.

 

The authors noted two limitations of the review. None of the studies were randomized controlled trials because it was deemed unethical to randomly remove pregnant women from drug treatment. Additionally, they noted that many women stop antidepressant use after discovering they are pregnant, which made it "difficult to characterize the 'exposed' group."

 

The authors declared no funding or conflicts of interest for their study.

 

Primary source: Human Reproduction

Source reference:

Domar AD, et al "The risks of selective serotonin reuptake inhibitor use in infertile women: a review of the impact on fertility, pregnancy, neonatal health, and beyond" Hum Reprod 2012; DOI: 10.1093/humrep/des383.

[Barbarannamated]

I've read a few responses to this study from OB/GYNs. They seem defensive, scared, and are trying to discredit the article and data. It struck me that they are possibly more invested in these drugs than psychiatrists. Liability?

 

I especially like this part of article:

 

"The authors declared no funding or conflicts of interest for their study."

[Altostrata]

My gyn stopped prescribing antidepressants some years ago, after I sent her a few articles about dangers to newborns.

 

She hates pharmapsychiatry as much as we do.

[dalsaan]

Could be liability. Could also just be good old fashioned ego. A lot of 'experts' don't like to have their knowledge challenged.

[Barbarannamated]

Could be liability. Could also just be good old fashioned ego. A lot of 'experts' don't like to have their knowledge challenged.

 

Definitely ego, Dalsaan.

 

My thought on liability... I believe OB/GYN has the highest malpractice insurance because they can be held liable for babies they deliver up to the age of 18 (differs by state). Many OB/GYNs are leaving the field or limiting their practice to gynecology.

 

That said, it's very difficult to prove that SSRIs (or any exposure in utero) caused a developmental or neurobehavioral disorder that is diagnosed years after birth. As long as the drugs remain on the market with only minor warnings, I don't foresee significant change.

 

Heck, it ensures a new generation of patients needing drugs. Sorry... my cynicism precedes me.

 

I hope that, at the very least, a black box or stronger warning is put in prescribing info. It's amazing to me that there have been successful lawsuits about birth defects, but people still use the drugs. Apparently that info is not reaching the public or is being played down by docs. I don't have kids, so have never been forced to give this much thought.

 

Alto, I like your doctor!

[Altostrata]

Me, too. She's one of the best in the state.