June 2, 2010 -- A Canadian study of more than 5,000 women shows an association between taking antidepressants, particularly the selective serotonin reuptake inhibitors (SSRIs) such as Paxil, Prozac, and Zoloft, and an increased risk for miscarriage. But researchers caution that this association does not imply a cause-and-effect relationship.
The study is published in the June issue of the Canadian Medical Association Journal.
Researchers from the University of Montreal and the CHU Sainte-Justine Mother and Child University Hospital in Montreal analyzed population data from the Quebec Pregnancy Registry. They identified 69,742 pregnant women from the registry, including 5,124 women who had had a miscarriage during the first 20 weeks of pregnancy; 51,240 women who did not have miscarriages served as a comparison group in the study.
The women ranged in ages from 15 to 45. The data were collected between 1998 and 2003.
Among those who had miscarried, 5.5% had taken antidepressants. Compared with the women who had not miscarried, those who had were more likely to be older, live in an urban environment, be recipients of social assistance, have a diagnosis of depression or anxiety, have visited a psychiatrist in the year prior to pregnancy, have had longer duration of exposure to antidepressants, and have had diabetes and/or asthma.
Overall, the analysis showed:
- A 68% increased risk in miscarriage in pregnant women using any class of antidepressant drugs compared with women who had never used antidepressants.
- A 61% increased risk among those who used SSRIs.
- A 75% increased risk of miscarriage associated with the SSRI Paxil.
- A 19% increased risk of miscarriage among those who had a history of depression.
There was also an independent risk associated with Effexor, part of the class of antidepressants called serotonin norepinephrine reuptake inhibitors.
"Animal studies had shown that rats were aborting more frequently when they were using antidepressants," Anick Bérard, PhD, director of the research unit on medications and pregnancy at the University of Montreal and senior study author, tells WebMD in an email. "No human study had looked at classes, types, and dosages of antidepressants and the risk of spontaneous abortions."
Although any kind of exact biological mechanism remains unclear, Bérard says "it is believed that antidepressants have a mediated serotonin effect that would put pressure on the uterus at a very early stage of pregnancy."More research would be needed to flesh out any biological connection.
According to the researchers, antidepressants are widely used in pregnancy and up to 3.7% of women will use them at some point during the first trimester. However, discontinuing treatment can cause problems since depression can put both the mother and baby at risk. In the U.S., there are about 6 million pregnancies every year, and there are 2 million pregnancy losses including about 600,000 due to miscarriage in the first 20 weeks of gestation.
In an accompanying editorial, Adrienne Einarson, assistant director of the Motherisk Program at The Hospital for Sick Children, writes that there is no "gold standard for studying the safety of drugs during pregnancy, because all methods have strengths and limitations." However, she notes she encountered similar findings in her own research. "Clearly, this study cannot make any definitive conclusions as to whether antidepressants increase the risk of spontaneous abortion."
David L. Keefe, MD, is a psychiatrist and chairman of the department of obstetrics and gynecology at New York University Langone Medical Center. Keefe cautions that there is no need to change treatment recommendations.
"The strength of the study is that it used a large sample size. The other strength is that they used a database to determine if women actually took the medication, so they didn't use individual recall, which can be biased," Keefe tells WebMD. "But they didn't control for the other factors that can also contribute to miscarriage."
Keefe says that women who use antidepressants tend to be older, smoke, and are obese, all factors that can contribute to miscarriage and also factors that may be seen among women with depression. "You need to control for age, smoking, and weight and then see if this association still holds up."
"The depression itself might increase the risk of miscarriage because of the stress on the body," he says. "This is the first paper I've seen to claim an association, but I'm not convinced. There's a lot more work to be done."
Drug Company Perspective
"Our medical team has not completed its review of the Canadian Medical Association Journal article and therefore it would be premature for us to comment on this particular study," says GlaxoSmithKline spokeswoman Sarah Alspach, in an email to WebMD. GlaxoSmithKline is the maker of Paxil.
"It is unfortunate," says Alspach, "but approximately 10% to 15% of all confirmed pregnancies end in miscarriage before 20 weeks. [Paxil] is approved for use in adults with depression, and has shown a clear clinical benefit for those patients. The prescribing information contains information and warnings about the use of [Paxil] during pregnancy, and advises that doctors should only prescribe [Paxil] if the potential benefit outweighs the potential risk. Globally, GSK [GlaxoSmithKline] proactively monitors reports of adverse events experienced by people taking its medicines and updates the prescribing information as appropriate when new information is developed."
WebMD also contacted Pfizer, the maker of Effexor. "Pfizer will need to review this study in detail until we can provide any further comment," Pfizer spokesperson MacKay Jimeson tells WebMD. "In the UK, there is no adequate data for the use of [Effexor] in pregnant women. If patients or their carers are concerned about any aspect of their medication, they should consult their doctor immediately."