Selective serotonin reuptake inhibitor use in pregnant women; pharmacogenetics, drug-drug interactions and adverse effects

Introduction: Possible negative effects of selective serotonin reuptake inhibitors (SSRIs) in pregnancy relate to congenital anomalies, negative perinatal events and neurodevelopmental outcome. Many studies are confounded by the underlying maternal disease and by pharmacogenetic and pharmacokinetic differences of these drugs. Areas covered: The possible interactions of SSRIs and serotonin and norepinephrine reuptake inhibitors with other drugs and the known effects of SSRIs on congenital anomalies, perinatal and neurodevelopmental outcome. Expert opinion: SSRIs should be given with caution when combined with other drugs that are metabolized by cytochrome P450 enzymes. SSRIs apparently increase the rate of severe cardiac malformations, induce neonatal adaptation problems in up to 30% of the offspring, increase the rate of persistent pulmonary hypertension of the newborn and possibly slightly increase the rate of prematurity and low birth weight. Most neurodevelopmental follow up studies did not find significant cognitive impairments except some transient gross motor delay, slight impairment of language abilities and possibly behavioral changes. The literature on the possible association of SSRIs with autism spectrum disorder is inconsistent; if an association exists, it is apparently throughout pregnancy. The risk associated with treatment discontinuation seems to outweigh the risk of treatment, as severe maternal depression may negatively affect the child’s development. If needed, treatment should continue in pregnancy with the minimal effective dose.