The prevalence of depression during pregnancy is 10–20 %. Treatment includes the use of antidepressants, which can cross the human placenta and harm the fetus. On the other hand, untreated depression is also associated with increased risk of negative pregnancy outcomes.
The aim of this thesis is to systematicaly review the existing literature on the safety of antidepressant use during pregnancy. This review aims to determine whether prenatal antidepressant exposure is associated with congenital malformations, adverse neonatal and pregnancy outcomes, long-term neurobehavioral development and also whether there are differences in safety between individual groups of antidepressants.
We searched the database MEDLINE (PubMed) using the following criteria: English language articles published after 2000, studies conducted on humans, systematic reviews and meta-analysis. We interpreted the safety of antidepressants based on ATC classification.
Twenty-six meta-analyses and thirty-two systematic reviews were included in this thesis. The results suggest that the use of antidepressants during pregnancy is not a risk factor for congenital malformations in general, but there appears to be a significant association with specific malformations, such as cardiovascular defects and septal defect. Further, the use of antidepressants was associated with a significantly increased risk for spontaneous abortion and other adverse pregnancy outcomes. Gestational age for fetuses exposed to antidepressants was shorter for approximately 3 days, birth weight lower for 75 grams and Apgar scores lower for slightly less than half a point. Moreover, the use of antidepressants in a third trimester appears to be significantly associated with poor neonatal adaptation syndrome. Long-term studies on neurobehavioral outcomes of in utero antidepressant exposure suggest potential negative effects on motor function and IQ score when SSRIs or venlafaxine were used. The highest risk was observed when paroxetine was used. This medicine was associated with congenital defects, specifically cardiovascular defects, atrial septal defects, right ventricular outflow tract obstruction and cleft palate. Fluoxetine was significantly associated with neural tube defects, citalopram with hypospadias and sertraline with septal defects as well as club-foot. Among the TCAs, clomipramine was associated with congenital heart defects while amitryptiline with limb anomalies. Bupropion significantly increased the risk for left ventricular outflow tract obstruction and ventricular septal defects, while venlafaxine for hypospadias and neural tube defects.
In pregnant women the risk and benefits of antidepressant use during pregnancy should be weighted. If a woman is experiencing severe symptoms of depression quitting treatment is not recommended as the depression itself may be a risk factor for adverse pregnancy outcomes. Antidepressants with the least adverse effects are from the TCAs and SSRIs groups, mainly sertraline, citalopram, nortryptiline and desipramine. The use of paroxetine should be avoided during pregnancy.
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