Weighing new evidence on SSRI use.(DRUGS, PREGNANCY, AND LACTATION)

Until fairly recently, studies and reviews of global teratovigilance data have been relatively reassuring that SSRIs were particularly safe, especially with regard to their teratogenicity. In fact, there are more reproductive safety data available for SSRIs than for many medicines women take during pregnancy. However, new reports have raised concerns regarding the teratogenicity of paroxetine, which we have previously discussed (OB.GYN. NEWS, Oct. 15, 2005, p. 9), as well as risk for putative neonatal distress syndromes and, most recently, possible increased rates of persistent pulmonary hypertension of the newborn (PPHN) following late-pregnancy exposure to SSRIs.

What do the new reports describe and how do the findings inform clinical care? One study supports previous reports of a "neonatal abstinence syndrome" with characteristic symptoms of jitteriness, sleep disturbance, dysregulation, tachypnea, and myoclonus in infants whose mothers used antidepressants during pregnancy. In this prospective cohort study of 120 infants, examiners used a systematic scale to assess full-term SSRI-exposed newborns with respect to presence or absence of a wide range of previously reported symptoms.

Of the 60 infants exposed in utero to various SSRIs for a mean of 35.5 weeks, 8 had severe symptoms and 10 had mild symptoms, compared with none of the 60 infants who had not been exposed in utero to these drugs (Arch. Pediatr. Adolesc. Med. 2006;160:173-6). A particularly noteworthy finding is that no infant with symptoms required treatment intervention; symptoms were transient and of little if any clinical significance.

In the second study, investigators using a case-control design described an elevated risk for PPHN, a far more serious syndrome associated with severe respiratory failure, in newborns with in utero exposure to SSRIs late in pregnancy. In this study, which enrolled almost 400 women whose infants had PPHN, matching them to more than 800 control mothers and infants, the use of SSRIs at any point during pregnancy was not associated with PPHN, but there was a significant association between PPHN and in utero exposure to an SSRI after 20 weeks' gestation (N. Engl. J. Med. 2006;354:579-87).

The study describes a very disturbing and striking finding. But an accompanying editorial points out that the number of cases reported is small (N. Engl. J. Med. 2006;354:636-8). And though not mentioned in the editorial, the vulnerability to reporting bias in such a study is great. One wonders whether women without an ...