Long-term Effects of Fetal Exposure to Antidepressants

Long-term Effects of Fetal Exposure to Antidepressants

Although data accumulated over the last 30 years suggest that some medications may be used safely during pregnancy, our knowledge regarding the risks of prenatal exposure to psychotropic medications is incomplete. Because neuronal migration and differentiation occur throughout pregnancy and into the early years of life, the central nervous system (CNS) remains particularly vulnerable to toxic agents throughout pregnancy. While insults that occur early in pregnancy may result in gross abnormalities, exposures that occur after neural tube closure (at 32 days of gestation) may produce more subtle changes in behavior and functioning.

Behavioral teratogenesis refers to the potential of a psychotropic drug administered during pregnancy to have long-term neurobehavioral effects. For example, are children who have been exposed to an antidepressant in utero at risk for cognitive or behavioral problems at a later point during their development? Animal studies demonstrate changes in behavior and neurotransmitter function after prenatal exposure to a variety of psychotropic agents. The extent to which these findings are of consequence to humans has yet to be demonstrated. To date, only two studies have systematically investigated the impact of exposure to antidepressants in utero on development and behavior in humans.

In a landmark study, Nulman and colleagues (1997) followed a cohort of children up to preschool age who had been exposed to either tricyclic antidepressants (n=80) or fluoxetine (n=55) during pregnancy (most commonly during the first trimester) and compared these subjects to a cohort of non-exposed controls (n=84). Results indicated no significant differences in IQ, temperament, behavior, reactivity, mood, distractibility, or activity level between exposed and non-exposed children. A more recent report from the same group which followed a cohort of children exposed to fluoxetine (n= 40) or tricyclic antidepressants (n=47) for the entire duration of the pregnancy yielded similar results (Nulman et al, 2002). The authors concluded that their findings support the hypothesis that fluoxetine and tricyclic antidepressants are not behavioral teratogens and do not have a significant effect on cognitive development, language or behavior. In contrast, they observed that depression in the mother is associated with lower cognitive and language achievement in the children. While these data are reassuring, it is important to note that the findings are preliminary. Clearly further investigation into the long-term neurobehavioral effects of prenatal exposure to antidepressants, as well as other psychotropic medications, is warranted.

Ruta Nonacs, M.D., Ph.D.

Nulman I, Rovet J, Stewart DE, et al: Neurodevelopment of children exposed in utero to antidepressant drugs. N Engl J Med 1997; 336: 258-262.

Nulman I, Rovet J, Stewart DE, Wolpin J, Pace-Asciak P, Shuhaiber S, Koren G. Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Am J Psychiatry. 2002; 159: 1889-95.

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