May 15, 2003
May 1, 2003 from ObGynNews By Lee S. Cohen, M.D.
The increasing number of reproductive-age women who are on antidepressants has raised concerns about the potential risks of teratogenicity, perinatal toxicity, and the long-term neurobehavioral sequelae of prenatal exposure to these medications. Literature over the last decade supports the absence of teratogenicity of selective serotonin reuptake inhibitors (SSRIs) and the older tricyclics.
Still, questions remain about the risks of short-term perinatal toxicity in newborns when antidepressants are used around the time of labor and delivery. These concerns date back 20 years, when case reports suggested that maternal use of tricyclics near term was associated with problems in the newborn such as difficulty feeding, restlessness, or jitteriness.
More recent studies have suggested that peripartum exposure to SSRIs may be associated with poor perinatal outcomes. One study found an association between the use of fluoxetine (Prozac) during the third trimester and a greater risk of neonatal complications (N. Engl. J. Med. 335:1010-15, 1996).
Concerns have been raised about the study’s methodology, however: The study was not blinded so examiners knew the babies had been exposed to medication. In addition, the study did not control for maternal mood disorder during pregnancy.
Two more recent studies of perinatal effects associated with third-trimester exposure to antidepressants have generated many questions. The first, conducted by investigators at the Motherisk Program at the University of Toronto, compared 55 newborns exposed to paroxetine (Paxil) late in pregnancy with a control group of newborns exposed to paroxetine early in pregnancy and newborns exposed to nonteratogenic drugs. There was a significantly higher rate of neonatal complications among paroxetine-exposed newborns, resolving in 1-2 weeks. Respiratory distress was the most common adverse effect (Arch. Pediatr. Adolesc. Med. 156:1,129-32, 2002).
The authors posit that the unexpectedly high rate of symptoms in these newborns may be the neonatal equivalent of the discontinuation syndrome commonly seen in adults who develop a variety of somatic symptoms after rapidly stopping paroxetine. While this is an interesting study consistent with some but not all previous reports, it has obvious methodologic limitations: Information was obtained through telephone interviews rather than direct blinded observation, and the well-described effects of maternal mood during pregnancy on neonatal outcome were not considered. Depression during pregnancy has been independently associated with adverse neonatal affects, including low birth weight, small-for gestational-age babies, and increased obstetrical complications.
The second study compared neonatal outcomes following in utero exposure to tricyclics and SSRIs using a large database from a group-model HMO. The malformation rate was not increased among those exposed to antidepressants in utero, but there was an association between third-trimester exposure to SSRIs and lower 5-minute Apgar scores and decreases in mean gestational age and birth weights; these differences were not observed among tricyclic-exposed newborns (Am. J. Psychiatry 159:2055-61, 2002). At ages 6 months and up, there were no significant differences between the groups, despite the differences noted at birth, and exposure to SSRIs or tricyclics was not associated with developmental delays through age 2. As in the previous study, maternal mood during pregnancy was not assessed.
Given the methodologic weaknesses of these studies, one cannot conclude that the use of antidepressants is associated with compromised perinatal outcomes. The findings from these two studies may be a signal of a potential problem. But pending more controlled study, appropriate vigilance of exposed newborns is good clinical care versus arbitrary discontinuation of antidepressants during the peripartum period.
Treatment decisions need to be made in the context of yet to be qualified relative risk (if any) for perinatal sequelae
exposure to antidepressants at term versus the increased risk for adverse neonatal outcomes and postpartum depression associated with pregnancy-associated maternal depression. Accumulated data regarding potential risks of perinatal exposure to antidepressants do not appear to justify lowering the dose of these agents or stopping these medicines around labor and delivery. Doing so may increase risk for depression in the mother and the impact of affective dysregulation on the newborn.
The findings of the two studies are clearly of interest and demand further prospective inquiry. Until results of such studies are available, clinicians should share available information with patients, so together they can make informed decisions regarding the use of antidepressants across pregnancy.
DR. LEE COHEN is a psychiatrist and director of the perinatal psychiatry program at Massachusetts General Hospital, Boston. Related information is available on the program’s web site at www.womensmentalhealth.org.