Are the new SSRIs safe for pregnant women?

Nathalie A. Kulin, MSC; Anne Pastuszak, MSC; Gideon Koren, MD, FRCPC

October, 1998

A decade after introduction of the first selective serotonin reuptake inhibitor (SSRI), fluoxetine (eg, Prozac), into clinical use, this class of antidepressants is being used by millions of men and women worldwide. Because more than half of all pregnancies are unplanned, and because an estimated 8% to 20% of all women suffer from depression, fetal safety is a primary concern when antidepressants are prescribed.

During the last few years, new SSRIs with purportedly fewer adverse effects than fluoxetine have been introduced into the market. ^1-3 While many women of reproductive age use the newer SSRIs for depression and other indications (such as obsessive-compulsive disorder), no data on whether they are safe to use during pregnancy have been collected. The Motherisk Program has recently completed the first prospective, controlled, cohort study of pregnancy outcome following fetal exposure to the new SSRIs. ⁴

Patients and methods

The prospective cohort included all women who contacted one of nine participating Teratology Information Services regarding exposure to fluvoxamine (eg, Luvox), sertraline (Zoloft), or paroxetine (Paxil) during the first trimester of pregnancy. The primary end point of interest was rate of major malformations defined as structural or functional anomalies that have serious medical or social consequences.

A total of 267 women met the study inclusion criteria: 92 from Toronto; 66 from Tampa, Fla; 46 from Philadelphia, Pa; 32 from Farmington, Conn; 11 from Salt Lake City, Utah; seven from Burlington, Vt; six from London, Ont; four from Chicago, Ill; and three from Indianapolis, Ind. Of these 267 women, 147 used sertraline, 97 paroxetine, and 26 fluvoxamine; 49 women used SSRIs throughout pregnancy. Most women used sertraline at 50mg/d (range 25 to 250mg), paroxetine at 30mg/d (range 10 to 60mg), and fluvoxamine at 50mg/d (range 25 to 200 mg).

Research findings

Women exposed to SSRIs were significantly less likely to be primigravid, and significantly more likely to smoke cigarettes and to have had previous therapeutic abortions (Table1). These trends were similar for the three SSRIs.

Pregnancy outcome did not differ among the groups. There were similar rates of major malformations, spontaneous and elective abortions, and stillbirth. Mean birth weights were similar, as was gestation age (Table2). Outcomes for women who took SSRIs throughout pregnancy were similar to outcomes of those who took the drugs only during the first trimester. Smokers and non-smokers using SSRIs had similar outcomes (data not shown).

Our study confirms the results of animal experiments in showing that, when used in recommended doses, the new SSRIs do not appear to increase the risk of congenital malformations. Our sample was large enough to detect a relative risk of 2.5 for major malformations with a power of 80% and an a of .05.

References

1. Solvay Kingswood. Product information. Luvox. Scarborough, Ont: Solvay Kingswood; 1991.
2. SmithKline Beecham Pharmaceuticals. Product information. Paxil. Oakville, Ont: SmithKline Beecham Pharmaceuticals; 1995.
3. Pfizer Pharmaceuticals. Product information. Zoloft. Kirkland, Que: Pfizer Pharmaceuticals; 1994.
4. Kulin NA, Pastuszak A, Sage SR, Schick-Boschetto B, Spivey G, Feldcamp M, et al. Pregnancy outcome following maternal use of the new selective seratonin reuptake inhibitors. A prospective controlled multicenter study. JAMA 1998;279:609-10.