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Selective Serotonin Reuptake Inhibitor Exposure During Early Pregnancy and the Risk of Fetal Major Malformations: Focus on Paroxetine

Salvatore Gentile, M.D., and Cesario Bellantuono, M.D.

Objective: To analyze all studies reporting primary data on the rate of fetal malformations after early in utero exposure to paroxetine, investigated either specifically or jointly with other antidepressant medications.

Data Sources: Medical literature was identified through searches of MEDLINE/PubMed, TOXNET, EMBASE, and The Cochrane Library (1980 through September 2008). Search terms were pregnancy, antidepressants, SSRIs, paroxetine, and fetal malformations. Additional studies were identified from the reference lists of published articles.

Data Selection: Twenty-five articles reporting primary data on the rate of fetal structural malformations following exposure to paroxetine or selective serotonin reuptake inhibitors as a group during the first trimester of pregnancy were electronically or manually selected.

Data Synthesis: Studies on the teratogenic risk of paroxetine show a high degree of heterogeneity. Moreover, research studies performed with the same methodology and thus showing the same level of evidence report conflicting results.

Conclusion: Given the inconsistency of the findings and limitations of the methodology of the published studies, the teratogenic potential of paroxetine that has been reported in some studies remains unproven. This relevant safety question is likely to remain unanswered until large, prospective studies are conducted. Such studies should be designed to include a control group of untreated mothers with similar psychiatric diagnosis so as to differentiate effects of drug exposure from impact of underlying mental disorder on the fetus. Moreover, further experimental studies are warranted to definitively assess clinical consequences of the impact on fetal development related to physiologic effects of prenatal paroxetine exposure on different maternal and fetal parameters.


(J Clin Psychiatry 2009;70(3):414-422. Online Ahead of Print February 24, 2009. doi:10.4088/JCP.08r04468)

Received June 15, 2008; accepted Sept. 29, 2008. From the Department of Mental Health, Azienda Sanitaria Locale Salerno 1, Mental Health Center n. 4, Salerno (Dr. Gentile); and the Psychiatric Unit, Department of Neuroscience, Polytechnic University of Marche, United Hospitals, Ancona (Dr. Bellantuono), Italy.

No direct support was received for this review article.

Dr. Gentile has received honoraria from Eli Lilly and Boehringer Ingelheim; has been a member of the speakers or advisory board for Eli Lilly; and has received other financial or material support from AstraZeneca, GlaxoSmithKline, Lundbeck, Janssen-Cilag, Recordati, and Bristol-Myers Squibb. Dr. Bellantuono has received honoraria from and has been a member of the speakers or advisory boards for Eli Lilly, Bristol-Myers Squibb, and InnovaPharm.

Corresponding author and reprints: Salvatore Gentile, M.D., Department of Mental Health, ASL Salerno 1, Mental Health Center n. 4, Piazza Galdi, 841013 Cava de' Tirreni, Salerno, Italy (e-mail: