To the Editor.— Kulin et al1
reported the first prospective study of pregnancy outcome following maternal
use of the newer serotonin selective antidepressants. They describe a total
of 267 drug exposures in the first trimester and report that 49 women continued
to take a selective serotonin reuptake inhibitor (SSRI) throughout the pregnancy.
However, they do not describe the extent of the SSRI exposure during these
pregnancies. Sertraline, paroxetine, and fluvoxamine have relatively short
elimination half-lives: the half-life of fluvoxamine is 15.6 hours2; paroxetine, 21.0 hours3;
and sertraline, 26 hours,4 with its less
active metabolite n-desmethylsertraline having a
half-life of 62 to 104 hours. Thus, it is possible that women who discontinued
use of medication shortly after missing a period may have washed out the drug
and reduced fetal exposure to drug to less than 6 weeks. If this is the case,
it would seem premature to comment on the teratogenic risk of exposure to
these newer, shorter-acting SSRIs without a larger group of women who took
these medications throughout the first trimester. In addition, what conclusion
can be made regarding the reproductive safety of specific compounds such as
fluvoxamine, paroxetine, and sertraline when these agents were combined to
generate a sample size on which the risk estimates were based?