A new study adds to the debate over the use of antidepressant medications during pregnancy, a problem that many depressed women who become pregnant must face: should they continue to treat their illness despite the risks of the drugs to the fetus?
The new research, published in the Archives of General Psychiatry, finds that women who took antidepressants during pregnancy were more likely to have babies with reduced head size and had twice the risk of preterm birth, compared with depressed women who did not take medication. Women with untreated depression, in contrast, were more likely to have babies with both smaller body size and reduced fetal head growth. Nearly 8% of women take antidepressants while pregnant in the U.S.
The study involved nearly 8,000 pregnant women in the Netherlands who were asked about their depression symptoms and antidepressant use once per trimester. Antidepressant drugs included those in the same class as Prozac and Zoloft — the selective serotonin reuptake inhibitors, or SSRIs — and women’s use was confirmed by pharmacy records. Prenatal development was studied by ultrasound.
More than 7% of the mothers had significant depression but did not use these medications, while 1.3% took SSRIs.
The reduction in fetal head growth was greater in the SSRI group compared with that seen in the untreated group. The magnitude of the effect of antidepressant use on head size was between that seen in previous studies of tobacco and marijuana use in pregnancy. Smoking reduces fetal head growth by 0.13 millimeters per week, while SSRIs slowed it by 0.18 mm; marijuana use has the largest effect, at 0.21 mm.
It’s not clear what the long-term risks of reduced head size are, but previous studies have linked it to behavioral and psychiatric problems in later life.
The study also found that preterm birth was more common in women taking antidepressants: compared with 5.1% of women without depression and 6.3% of those with untreated depression who delivered prematurely, 10.1% of those taking SSRIs had a preterm birth. On average, untreated depressed women gave birth a day later than those who took the medications.
Most previous studies have not found increased odds of major birth defects associated with SSRIs, but some have linked these medications — particularly Paxil (paroxetine) — to elevated risks of heart defects and a dangerous lung condition called persistent pulmonary hypertension in which the baby’s circulation system doesn’t immediately adjust to working outside the womb.
But because such problems are rare and because depression itself can affect fetal development and prevent the mother from bonding with the baby after birth, the benefits of medication use are often seen as outweighing the risks in severe depression. Studies like the current one, which cannot randomize people to be treated or untreated, cannot further discern whether the people who took antidepressants had more severe depression, which could muddy the relationship between the drugs and fetal outcomes.
Dr. Gideon Koren, director of the Motherisk program in Canada, an organization that studies the risks of chemicals, drugs and diseases during pregnancy, believes the new study adds weight to the data favoring medication use. “Even treated depressed women often have residual depression, so this study strongly suggest that by treating depression, the overall risk for the fetus decreases,” he says. “It is very evident that the risks of unmanaged depression by far exceed those theoretical, and yet not proven risks of SSRIs (despite scores of studies).” Koren was not involved in the new research.
The authors reach a similar conclusion, writing:
Ideally, preconception health promotion and prevention programs should be developed to improve health of pregnant women and to reduce risk of developing prenatal depression. However, these programs will doubtless be ineffective for some women with prenatal depression in whom the benefits of antidepressant treatment with SSRIs probably outweigh the risks.
The study was funded by the Dutch government and medical organizations and the authors report no pharmaceutical industry funding. But the large role of industry funding in the overall literature on this question ensures that questions over when and whether to treat depression with medication during pregnancy remain difficult to resolve. “This is a carefully planned and well executed study on an important, unaddressed area,” says Koren.