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Katherine L. Wisner, MD, MS; Alan J. Gelenberg, MD; Henrietta Leonard, MD; Deborah Zarin, MD; Ellen Frank, PhD

JAMA. 1999;282:1264-1269.

Context  Despite the frequency of depression in women of childbearing age, information to guide patients and physicians through a consideration of treatment during pregnancy is limited.

Objective  To identify risk factors associated with treatment of major depression during pregnancy to help physicians develop treatment plans that optimize clinical care.

Data Sources  Reports of prospective controlled trials in English were identified from MEDLINE and Health STAR using the search terms antidepressant during pregnancy and depression during pregnancy, by manually searching bibliographies of review articles, and through discussions with investigators for 1989-1999.

Study Selection  We selected studies in which maternal and infant health outcomes associated with antidepressant exposure were compared with those of nonteratogen-exposed controls. Four studies published since 1993 were identified and included in the analysis.

Data Extraction  We abstracted information about identification of subjects, comparison groups, pregnancy, and birth outcomes. We organized the data along 5 domains of reproductive toxicity: intrauterine fetal death, morphologic teratogenicity, growth impairment, behavioral teratogenicity, and neonatal toxicity.

Data Synthesis  Data were available for tricyclic antidepressants (collectively), fluoxetine, and newer selective serotonin reuptake inhibitors (collectively). Exposure to these agents did not increase risk for intrauterine death or major birth defects. Decreased birth weights of infants exposed to fluoxetine in the third trimester were identified in 1 study. The development of children whose mothers took tricyclics or fluoxetine during gestation did not differ from that of controls. Direct drug effects and withdrawal syndromes occurred in some neonates whose mothers were treated with antidepressants near term.

Conclusions  Although few in number, new information from prospective studies provides a welcome change from decision making based on nonprospective data. Monitoring and interventions for patients with identified risks (eg, poor weight gain) are recommended.

Author Affiliations: Case Western Reserve University School of Medicine, Cleveland, Ohio (Dr Wisner); Department of Psychiatry, School of Medicine, University of Arizona Health Sciences Center, Tucson (Dr Gelenberg); Department of Psychiatry and Human Behavior, Brown University School of Medicine, Providence, RI (Dr Leonard); American Psychiatric Association, Washington, DC (Dr Zarin); and Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, Pa (Dr Frank).

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