Rates of Major Malformations in Infants Following Exposure to Duloxetine During Pregnancy

Abstract

To the Editor: There are no published prospective, comparative studies examining the safety of duloxetine in pregnancy, and, to date, there are only 2 case reports describing its use in pregnancy:(1) a 29-year-old woman was treated with duloxetine for depression during the second half of pregnancy and gave birth to a full-term healthy infant, 1 and (2) an infant was observed after birth with signs of possible poor neonatal adaptation, following exposure in utero to duloxetine in late pregnancy. 2 Here, we report the results of an international collaboration designed to evaluate the safety of this medication during pregnancy. Our main objective was to determine whether the use of duloxetine during the first trimester of pregnancy is associated with an increased risk for major malformations above the baseline of 1%-3%. Method.In this observational multicenter cohort study, data on duloxetine exposure were collected prospectively from either women or their health care providers who had requested information regarding the use of duloxetine during pregnancy. These data came mainly from national teratogen information services that provide evidence-based information regarding the safety of and risks associated with drugs and other exposures during pregnancy. The data were collected from March 2010 to April 2012 and were from Canada, France, Israel, England, Italy, Australia, Switzerland, and Finland. French data were collected from several pharmacovigilance centers, which use procedures similar to those of teratogen information services, although requests are received mostly from physicians. The United Kingdom Teratology Information Service does not currently routinely collect data from women, as it is their health provider who makes the initial inquiry.During the initial contact, demographics, medical and obstetric histories, and details of drug exposure, as well as concurrent exposures to other substances, were recorded by teratogen information service staff on a standardized questionnaire. Then, shortly after birth to approximately 2 to 3 months after delivery, research assistants at the teratogen information services contacted women who had taken duloxetine during pregnancy and obtained their oral and/or written consent to complete the pregnancy outcome questionnaire.The study design included 2 comparison groups of equal numbers of women unexposed to duloxetine, who were chosen randomly: (1) women who were inquiring about exposure to other antidepressants and (2) women inquiring about an exposure not considered teratogenic, such as acetaminophen, antibiotics, or hair color. These women were matched to the duloxetine group for age and alcohol and tobacco use. The main outcome of interest was the presence or absence of major malformations (genetic and cytogenetic anomalies were excluded).This study was approved by the Research Ethics Board at The Hospital for Sick Children in Toronto, Ontario, Canada, and, for centers in the other countries, by local research ethics boards. In the United Kingdom, data collection is c...

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