Pregnancy is often fraught with complications, not least for women suffering from depression while carrying a child: new research suggests that women who take antidepressant medications during pregnancy may have an increased risk of miscarriage.
Scientists at the University of Montreal reported Monday, May 31, in the Canadian Medical Association Journal that women taking the drugs most often prescribed to treat depression and anxiety including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and the older tricyclics had a significantly higher risk of miscarriage than a matched control group of women who did not take antidepressants. The study is the first of its kind to analyze which antidepressants and which doses are most likely to be associated with spontaneous abortion. Led by Anick Bérard at the Faculty of Pharmacy at the University of Montreal, the research team also documented that two SSRIs, paroxetine (Paxil) and venlafaxine (Effexor), are associated with the greatest risk.
Bérard analyzed data from a pregnancy registry she established in Quebec that collects records on births and spontaneous abortions occurring in hospitals in the Canadian province. The study included 69,742 women from the registry, 5,124 of whom had had a clinically recorded miscarriage. Among the women who had miscarried, 5.5% had filled at least one prescription for an antidepressant during pregnancy, compared with 2.7% of the control group. Researchers calculated that antidepressant users had a 68% higher risk of miscarriage than nonusers, after controlling for other influences that could potentially confound the association.
Overall, the risk was greatest among women who combined the use of two or more classes of antidepressants. When researchers looked at the small amounts of data on patients using specific drugs, they found that those taking paroxetine alone had a 75% higher rate of miscarriage than women without depression, while women taking venlafaxine had a more than doubled risk. "To my knowledge, we are the only ones to go further and look at which class [of antidepressant] and which dosage increased the risk most," says Bérard.
However, the study was an observational one that looked retrospectively at data already collected, which means that it's possible that some part of the miscarriage risk picked up by Bérard can be ascribed to depression itself rather than the drugs used to treat it. Indeed, the authors acknowledge that some past research has shown that women who are depressed during pregnancy are at increased risk of spontaneous abortion. But while acknowledging that limitation of the current study, Bérard stresses that it's unlikely that such a large difference the 68% increase could be wholly attributable to underlying causes. "The effect is too big," she says, "and while it may explain a small portion, it wouldn't explain the totality of the effect."
Still, obstetricians are not ready to stop writing prescriptions for antidepressants. Taken together, research on the risks of using antidepressants and most other prescription drugs for expectant moms and their developing babies is limited and often inconsistent. Evidence for the risks associated with depression drugs has been increasing in recent years, however, with studies finding a link between the medications, particularly when used during the first trimester, and as much as a sixfold increase in lung, heart and other congenital birth defects in newborns. Bérard's study adds solid evidence for a new risk factor, but because it is an observational study, says Dr. Alex Vidaeff, director of research in the division of maternal-fetal medicine at the University of Texas Medical School at Houston, "with this level of evidence, immediate changes in practice may be ill-advised."
Such findings leave women with depression facing increasingly complicated treatment decisions when they are pregnant or considering starting a family. According to the American Congress of Obstetricians and Gynecologists (ACOG), depression during pregnancy is common: about 14% to 23% of pregnant women will experience depressive symptoms; in 2003, about 13% of women took an antidepressant at some point during pregnancy. But both antenatal depression and the use of antidepressant medications are associated with health risks to the newborn. Past studies have shown that pregnant women who are depressed are more likely to have premature births and low-birth-weight babies and that their infants are at increased risk of irritability, sleep problems and high blood levels of the stress hormone cortisol compared with babies born to mothers without depression.
As with many clinical decisions, depression treatment during pregnancy is a matter of balance. Experts advise women to discuss with their physician the severity of their depression or anxiety and weigh their past history of miscarriage before deciding whether to change medications or reduce their doses while carrying a child. For its part, the ACOG recommended in a 2009 report that women with severe depression stay on medication during pregnancy and that women who are psychiatrically stable may also be able to continue medication after consulting with their mental-health-care provider and obstetrician. Depressed women who are not taking antidepressants or are not helped by them should seek treatment, whether it is psychotherapy or other interventions that can help reduce symptoms of depression and anxiety.
Although Bérard's analysis did not include a side-by-side comparison of antidepressant use in alleviating women's depressive or anxiety symptoms, other research has documented the importance of maintaining such treatment for women who otherwise would struggle to function at their best, much less under the added stress of expecting a child.