Treatment of depressed pregnant women by selective serotonin reuptake inhibitors: Risk for the foetus and the newborn

Introduction. - This article is a review of literature data concerning the use of selective serotonin reuptake inhibitors (SSRIs) by depressed pregnant women. Literature findings. - The adverse effects for the foetus, the newborn and the child were evaluated. The prevalence of depression during pregnancy is of around 10 to 20% of the population of childbearing women. Depression is often misdiagnosed and underestimated in pregnant women. Starting a pharmacological treatment for depression in these women is not easy because data concerning the safety of antidepressants during pregnancy are still unclear. The non-treated pathology is associated with higher risk of maternal morbidity, including arterial hypertension, which could lead to preeclampsia or eclampsia, ideation and suicide attempts, and postpartum depression. Foetal development is also affected and adverse outcomes such as prematurity, tow birth weight, irritability, and sleep disorders are frequent. Pharmacological therapy is necessary when non-pharmacological treatment is insufficient. Suicide attempts and relapse of depression have been described when depressive women stopped their pharmacological treatment during pregnancy. Pregnant women diagnosed with depression must be treated. Selective SSRIs are now largely used in this pathology and have replaced tricyclic antidepressants because of fewer side effects. In general, drugs have a low teratogenic potential, only 4 to 5% of malformations are iatrogenic. Teratogenic risk is high between conception until the end of the second month of gestation. Safety of SSRIs treatment during pregnancy and potential risk for the foetus and newborn were unquestioned before publication, in the late 2005, of some alarming data concerning a possible teratogenic effect. Studies showed an increased risk for all congenital malformations with SSRIs and particularly with paroxetin. A few studies after 2005 have also found an association between prenatal exposure to SSRIs (especially paroxetin) and congenital malformations. However, other studies failed to demonstrate this association and the risk for cardiovascular malformations also does not seem to be significantly increased. Numerous studies in pregnant women have shown that SSRI treatments are associated with a significant increase of spontaneous abortion, preterm birth, and low birth weight. Exposure to SSRIs in late pregnancy has been associated with a three-fold increased risk of neonatal behavioural syndrome, including signs of withdrawal or serotonin impregnation. Restlessness, poor tone, respiratory distress, hypoglycaemia were the most frequent signs. These symptoms occur during the first days of life and are usually brief and not serious. Recent studies have also documented an increased risk of persistent pulmonary hypertension and cases of cerebral haemorrhage have been described. Data concerning a possible effect on motor and cognitive development at school age in children prenatally exposed to SSRIs are limited. Discussion. - Although a number of studies revealed that SSRIs are not teratogenic, some of them showed congenital malformations associated with use of these antidepressants; in particular an increased risk of cardiac defects with paroxetin. In practice, the potential risk implies that the decision to treat a pregnant woman with SSRIs (notably paroxetin) should be taken carefully; this means double-checking the diagnosis, the potential benefits, adverse effects and possible alternatives. Neonatal toxicity seems to be relatively frequent when SSRIs are prescribed during late pregnancy. For all depressed pregnant women, the severity of the depression must be taken into consideration before introducing a pharmacological treatment. When depressive women are already treated, studies have shown that antidepressants must be maintained during pregnancy to prevent relapse and suicide attempts. (C) L'Encephale, Paris, 2009.