Serotonin reuptake inhibitors in pregnancy and the risk of major malformations: a systematic review

Objective To review studies conducted to establish the risk of major congenital malformations in women exposed to serotonin reuptake inhibitors (SRIs) during the first trimester of pregnancy. Methods A literature research was conducted within PsychoINFO, EMBASE, MEDLINE and Cochrane databases from 1966 to October 2006, to identify studies assessing the risk of major malformations in infants whose mother was taking SRIs (SSRIs and SNRIs) during the first trimester of pregnancy. Results Fifteen studies were selected for the analysis: seven adopted a prospective cohort design and seven a retrospective design, of these one was a case-control study. Data Synthesis and Conclusions The reviewed studies suggest that exposure to fluoxetine, sertraline, citalopram and venlafaxine in early pregnancy is not associated with an increased risk of major congenital malformations. For paroxetine, recent data call for caution in prescribing such a drug in early pregnancy. For the other SRIs, the risk remains substantially undetermined, as data are so far scanty. Given this background, large prospective cohort studies are urgently needed to better assess the risk/benefit ratio of SRIs-treatment during pregnancy. Copyright # 2007 John Wiley & Sons, Ltd. key words—antidepressants; selective serotonin inhibitors (SRIs); pregnancy; major malformations.