title: Use of selective serotonin reuptake inhibitors during pregnancy and risk of major and cardiovascular malformations: an update.
abstract: General consensus exists about the need to avoid drug intake as much as possible during pregnancy due to the lack of thorough evidence about the safety of pharmacologic treatments during gestation for both mothers and fetuses. In this respect, the overall safety profile of selective serotonin reuptake inhibitors (SSRIs) in pregnancy remains unclear. This article reviews current evidence about the safety of each SSRI during pregnancy in order to describe their specific teratogenic potential, with a particular focus on major and cardiovascular malformations, and to verify whether such toxicity can be considered as a class effect. The literature review included controlled studies and meta-analyses (retrieved using PsychINFO, EMBASE, and Medline from January 1966 to May 2010) from which the risk of major and/or cardiovascular malformations associated with a specific SSRI (ie, fluoxetine, paroxetine, sertraline, citalopram, escitalopram, and fluvoxamine) could be estimated. Although there is evidence to support the association between birth defects and first-trimester exposure to paroxetine, findings from the studies reviewed suggest a teratogenic potential of the whole SSRI class, consistent with preclinical evidence. These teratogenic effects are mainly in the heart region, and they are often described as septal defects. It may be suggested that the higher frequency of teratogenic effects reported for paroxetine might depend on specific pharmacologic features of this drug compared with other SSRIs, although it is difficult to test this hypothesis. It is noteworthy that current evidence on SSRI teratogenicity stems from studies affected by several methodological weaknesses (ie, lack of investigations using control groups of untreated depressed mothers, confounding by indication, and recall bias). Accordingly, we are not yet able to rule out the possibility that positive associations, as determined in some studies, result from analyses of poor quality.
authors.affiliation: Unit of Pharmacology, University Hospital of Pisa, Pisa, Italy. m.tuccori@ao-pisa.toscana.it
authors.forename: Marco
authors.initials: M
authors.lastname: Tuccori
authors.forename: Sabrina
authors.initials: S
authors.lastname: Montagnani
authors.forename: Arianna
authors.initials: A
authors.lastname: Testi
authors.forename: Elisa
authors.initials: E
authors.lastname: Ruggiero
authors.forename: Stefania
authors.initials: S
authors.lastname: Mantarro
authors.forename: Carla
authors.initials: C
authors.lastname: Scollo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pergola
authors.forename: Matteo
authors.initials: M
authors.lastname: Fornai
authors.forename: Luca
authors.initials: L
authors.lastname: Antonioli
authors.forename: Rocchina
authors.initials: R
authors.lastname: Colucci
authors.forename: Tiberio
authors.initials: T
authors.lastname: Corona
authors.forename: Corrado
authors.initials: C
authors.lastname: Blandizzi
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D018376:Cardiovascular Abnormalities / Q000139:chemically induced*; D015283:Citalopram / Q000009:adverse effects; D003863:Depression / Q000188:drug therapy*; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects; D016666:Fluvoxamine / Q000009:adverse effects; D006801:Humans; D008431:Maternal-Fetal Exchange; D017374:Paroxetine / Q000009:adverse effects; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D020280:Sertraline / Q000009:adverse effects; D013723:Teratogens
chemical_list: D015283:Citalopram; D005473:Fluoxetine; D016666:Fluvoxamine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D013723:Teratogens