Selective Serotonin Reuptake Inhibitors in Human Pregnancy: To Treat or Not to Treat? Study Sheds Light

A number of SSRIs were introduced, including fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, and escitalopram. They have better efficacy, tolerability, and safety compared to first-generation antidepressants, such as tricyclic antidepressants, and are safer in overdose.

SSRIs exert their effects by inhibiting the presynaptic plasma membrane serotonin transporter. This transporter mediates the reuptake of serotonin into the presynaptic terminal; neuronal uptake is the primary process by which neurotransmission via 5-hydroxytryptamine, or neuronal serotonin, is terminated.

Thus, treatment with an SSRI initially blocks reuptake and results in enhanced and prolonged serotonergic neurotransmission. All SSRIs share a similar mechanism of action despite having different chemical structures.

The use of antidepressants and anxiolytics has shifted from the domain of psychiatry to primary care with the discovery of more selective and safer drugs. SSRI use in pregnancy has increased over the years.

SSRIs readily cross the human placenta. Despite the widespread use of SSRIs during pregnancy and the relatively extensive literature available, there are conflicting views on the safety of these drugs during pregnancy.

The purpose of this traditional literature review is to summarize and evaluate the current evidence for the risk-benefit analysis of SSRI use in human pregnancy.

Human Studies on SSRIs in Pregnancy

Despite some troubling associations between SSRIs and major malformations, especially cardiovascular malformations, the overall current scientific evidence has not fulfilled the criteria for proof of human teratogenicity of SSRIs.

Despite having over 33,000 reported pregnancy outcomes after prenatal exposure to various SSRIs, differences in study design and conflicting results remain confusing. Further well-designed epidemiologic studies, with sufficient power and good control of potential confounders, may help verify whether SSRIs are associated with a small increased teratogenic risk, especially regarding cardiovascular anomalies.

In our opinion, the current data do not support teratogenicity of SSRIs.

Miscarriage, Intrauterine Growth Restriction (IUGR), and Preterm Delivery

Some studies found associations between SSRI use during pregnancy and the risk of miscarriage, IUGR, or preterm delivery. Most of these studies are potentially confounded by gestational age at initial contact and by the underlying psychiatric disorder.

Neonatal Effects

Neonatal symptoms were initially described following prenatal exposure to fluoxetine and later after exposure to paroxetine and other SSRIs. Neonatal toxicity or discontinuation syndromes associated with SSRIs are characterized by irritability, abnormal crying, tremor, and poor neonatal adaptation, including respiratory distress, tachypnoea, jitteriness, lethargy, poor tone or colour, and, rarely, convulsions. Most symptoms are mild and transient.

It can be concluded that SSRI use late in pregnancy, similar to many other psychotropic drugs, is associated with transient neonatal effects.

Persistent Pulmonary Hypertension of the Newborn

An absolute risk of less than 1% for persistent pulmonary hypertension of the newborn (PPHN) in infants exposed to SSRIs cannot be excluded, although studies are not consistent.

Neurodevelopmental Effects

In most studies focused on the possible neurodevelopmental effects of prenatal SSRI exposure, there is no conclusive evidence for an increased risk of adverse long-term effects.

Risk of Treatment Discontinuation

When evaluating the risk-benefit ratio of SSRI treatment in pregnancy, the risks associated with treatment discontinuation should also be considered. Abrupt discontinuation of psychotropic drugs in pregnancy is associated with physical and psychological adverse effects.

SSRI treatment discontinuation during pregnancy is associated with a higher frequency of relapse. Depression is associated with an increased risk of preterm delivery, and this risk increases with the severity of depression.

Treated women have lower depressive symptom scores and better functioning. These risks should be considered when deciding whether to continue treatment during pregnancy.

Clinicians are faced with the difficult cost-benefit decision of whether to recommend treatment for maternal depression or anxiety with SSRIs during pregnancy.

In teratology, decisions about new medications during pregnancy often need to be made with insufficient human pregnancy experience on safety. In the case of SSRIs in pregnancy, despite extensive available studies, quality is more important than quantity, and the data are still not conclusive.

In summary, most studies on SSRI use during pregnancy support that they are not major human teratogens. A small increased risk of cardiovascular anomalies, especially with paroxetine, cannot be excluded.

There appears to be a small increased risk of miscarriage, which may be associated with the underlying maternal condition. Neonates of mothers treated with SSRIs should be closely followed up after delivery because there is an increased risk of transient neonatal effects.

There is no conclusive evidence for adverse long-term neurodevelopmental effects of prenatal SSRI exposure. Discontinuation of treatment may pose risks, such as a higher frequency of relapse and an increased risk of preterm delivery.

Overall, the benefits of treatment seem to outweigh the potential small risk of untoward effects on the embryo, fetus, or neonate.

Source: Hindawi Publishing Corporation Obstetrics and Gynecology International Volume 2012, Article ID 698947 doi:10.1155/2012/698947