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June 17, 1998

Risk of Fetal Anomalies With Exposure to Selective Serotonin Reuptake Inhibitors

Author Affiliations

Margaret A.WinkerMD, Senior EditorIndividualAuthorPhil B.FontanarosaMD, Senior EditorIndividualAuthor

JAMA. 1998;279(23):1873. doi:10-1001/pubs.JAMA-ISSN-0098-7484-279-23-jbk0617

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?

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