SSRIs Deemed Safe During Pregnancy in Two Major Studies

Editor, Primary Psychiatry and Psychiatry Weekly, Professor of Psychiatry, New York University School of Medicine

First published in Psychiatry Weekly, Volume 2, Issue 28, on July 23, 2007

Decisions involving the use of prescription medications during pregnancy are difficult to make—for both mothers and their physicians. Needless to say, the potential benefits of a drug need to be balanced against its risks, both known and unknown. In the case of the SSRIs, making the correct choice has been difficult because of evidence showing that there is an increased risk of cardiac malformations associated with the use of paroxetine. Two years ago, the FDA issued an alert that paroxetine had been found to increase the risk of heart defects when it was taken during the first three months of pregnancy.¹ Paroxetine product information contains a warning that it may cause heart defects in fetuses.

Two new studies, however, involving nearly 30,000 infants failed to find a connection between heart defects and SSRIs as a group. The studies did find that there were some risks, but that they are small and not necessarily linked to all drugs in the class.The researchers found that women who took paroxetine during pregnancy were about twice as likely to have children with right ventricle obstructions. Still, the defect is rare even in children exposed to SSRIs.

One of the studies³ detected a slightly increased risk of three birth defects associated with SSRIs as a class, with specific antidepressants exhibiting a slightly increased risk of certain birth abnormalities: the risk of anencephaly was increased in women taking paroxetine; craniosyntosis occurred more commonly than among than those unexposed to SSRIs, and was not linked to any specific SSRI, and sertraline use was associated with a higher incidence of omphalocele. However, since these defects are rare in the general population to begin with, the overall risk is still low. Both studies found a moderate but significant relationship between paroxetine specifically and right ventricular outflow tract lesions.

There were some differences in the findings of the two studies. Alwan and colleagues² found significantly increased risks for craniosynostosis, omphalocele, and anencephaly, but not spina bifida, in association with exposure to SSRIs as a group. In contrast, Louik and colleagues³ found no relationship between SSRI exposure and craniosynostosis, omphalocele, or neural-tube defects as a group.

I often wonder if aspirin or penicillin would be brought to market in today’s regulatory and legal climate, and whether these drugs would have difficulty gaining approval. Articles would surely appear about anaphylactic reactions and opportunistic infections among some patients treated with penicillin. There might be case reports of people bleeding to death after an accident because of aspirin’s anticoagulant effect or of patients developing Guillain-Barré syndrome.

We need to be reminded that the benefits and risks of treatment should be kept in perspective. As Greene notes in an editorial accompanying the studies, all available information, including the newly published studies, “suggest that any increased risks of these malformations in association with the use of SSRIs are likely to be small in terms of absolute risks.”⁴ He adds that SSRIs, either collectively or as individual agents are not major teratogens. They are, however, very effective antidepressants and anxiolytics.

1. Use of paroxetine in first trimester of pregnancy may have a small increased risk of birth defects, compared to other antidepressants. Ottawa: Health Canada, October 2005. http://hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/public/2005/paxil_3_pa-ap_e.html. Accessed June 7, 2007.
2. Alwan S, Reefhuis J, Rasmussen SA. Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. N Engl J Med. 2007;356(26):2684-2692.
3. Louik C, Lin AE, Werler MM. First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. N Engl J Med 2007;356(26):2675-2683.
4. Greene, MF.  Teratogenicity of SSRIs--serious concern or much ado about little? N Engl J Med. 2007;356(26):2732-2733.

Disclosure: Dr. Sussman has received honoraria from AstraZeneca, Bristol-Myers Squibb, and GlaxoSmithKline.