NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Fluoxetine.

Abstract

The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for fluoxetine to cause adverse effects on reproduction and development in humans. Fluoxetine (Prozac(R); Serafemtrade mark) was selected for evaluation because of 1) sufficient reproductive and developmental studies, 2) human exposure information, 3) changing prescription patterns, and 4) public concern about potential reproductive and/or developmental hazards associated with exposure. Fluoxetine, an antidepressant, is also prescribed to treat premenstrual dysphoric disorder and has recently been approved for use in 7-17 year-olds. The results of this evaluation on fluoxetine are published in an NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Fluoxetine, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to fluoxetine on human development and reproduction. First, there is some concern for developmental effects, specifically shortened gestation and poor neonatal adaptation at therapeutic doses (20-80 mg/day). This conclusion is based on evidence from human studies that fluoxetine produces an increased rate of poor neonatal adaptation and that fluoxetine exposure during pregnancy can result in a shortened gestation and reduced birth weight at term. Second, there is minimal concern for adverse reproductive effects in fluoxetine-exposed adults. Evidence from human studies show that therapeutic doses of fluoxetine may, in both men and women, result in reversible, impaired sexual function, specifically a delay in or an inability to achieve orgasm. Finally, there are insufficient data to draw conclusions on 1) an association between fluoxetine therapy in pregnant women and pregnancy loss; and 2) on how breast milk or therapeutic exposures to fluoxetine might affect development. In a study in mice, early fluoxetine exposure affected adult behavior. However, additional data are needed to confirm and extend these findings and determine if such effects might possibly occur in humans. NTP-CERHR monographs are transmitted to federal and state agencies, interested parties, and the public and are available in electronic PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919-316-4511).