Expert reviewObstetricsAntidepressant use during pregnancy: the benefit-risk ratio
Section snippets
Congenital malformations
Over the first 2 decades after the introduction of fluoxetine into practice, both dysmorphologic and neurobehavioral human studies did not detect consistent risks of congenital malformations with the drug itself or with newer SSRIs and SNRIs.3, 8, 9, 10 Because of the relatively limited sample size of the initial studies, the common statement that described the fetal safety of these drugs was that they “do not appear to constitute major human teratogens.”
This school of thought changed with a
Pregnancy-induced pharmacokinetic and pharmacodynamic changes
In late pregnancy, there is an increased bodyweight that effectively decreases the dose per kilogram of antidepressants. Importantly, there is increased activity of several cytochrome enzymes, most notably CYP450 3A4 and CYP450 2D6, which catalyzes the metabolism of most SSRIs and SNRIs.59 Although this may lower serum concentrations of antidepressants, it is important to remember that often the drug is converted into an active metabolite, as in the case of venlafaxine and fluoxetine;
The risks of untreated depression
Uncontrolled depression in pregnancy has been associated with the increased risk of miscarriages, prematurity, and low birthweight.60 Critically, the strongest predictor of the life-threatening postpartum depression is depression in late pregnancy. Women who discontinue their antidepressants “cold turkey” because of fears of teratogenic effects exhibit higher rates of morbidity and hospitalization, which include suicide ideations and attempts and impaired adherence to medical therapy and
Monitoring depression symptoms in pregnancy
Although the depressed pregnant woman optimally should be treated by a psychiatrist, the obstetrician can have a unique opportunity to screen her for depressive symptoms. While in the waiting room for her appointment, the woman can complete the 5-minute Edinburgh Scale for depressive symptom (found online at http://www.fresno.ucsf.edu/pediatrics/downloads/edinburghscale.pdf). This 10-item questionnaire allows an estimation of depressive symptoms with high predictive values toward diagnosis
Perception of teratogenic risk
Pregnant women tend to perceive their teratogenic risk of medications as significantly higher than the true risk.65 Even in cases of exposure to nonteratogenic agents, women believe that their own child's risk for malformation is in the range of 25%, which is in the range of risk that was caused by thalidomide.65 Not surprisingly, it is common for pregnant women to avoid therapy, even for life-threatening medical conditions, or even to consider termination of otherwise wanted pregnancies.66
Benefit:risk ratio
Although over the last decade scores of original and review articles have discussed whether SSRIs-SNRIs possess a risk for congenital malformations (Table), very little has been done to integrate these potential risks, if they exist, into an overall context of benefit:risk ratio. Herein we will synthesize the components of risks and benefits of antidepressant use in pregnancy that should be considered in each case when the decision is being made to use or to avoid antidepressants during
Antidepressants during breastfeeding
Because they are molecules of relatively small molecular weight, all SSRIs-SNRIs cross the mammary gland to some extent into milk. In general, the extent to which a drug crosses into breast milk is quantified as the ratio of the dose per kilogram that is offered to the suckling baby through milk divided by the dose per kilogram that is taken by the mother.72 In the case of SSRIs-SNRIs, the relative infant dose is <5%, which makes it unlikely to cause adverse effects.73 In the context of
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The authors report no conflict of interest.