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

ABSTRACT

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.

KEYWORDS:

• Pregnancy
• SSRIs
• SNRIs
• pharmacokinetics
• anomalies
• neurodevelopment
• Autism
• maternal disease

Article Highlights

• Serotonin is a very important neurotransmitter involved in the development of the central nervous system and other organs. Hence, changes in fetal serotonin levels might have crucial implications on embryonic and fetal development.

• SSRIs and SNRIs seem to be used by 3–5% of pregnant women, especially those suffering from depression and/or anxiety.

• SSRIs and SNRIs increase serotonin synaptic levels. They are able to cross the placental barrier and possibly modify embryonic and fetal serotonin metabolism. The effects might be related to maternal and fetal pharmacogenomics and pharmacokinetics.

• SSRIs and SNRIs are not significant teratogens, although they may slightly increase the rate of congenital cardiac anomalies. They may also induce perinatal adaptation difficulties and some other complications.

• SSRIs and SNRIs do not seem to affect the neurodevelopmental outcome of the exposed offspring. The data on the possible association with Autism Spectrum Disorder is inconclusive.

• The risk associated with treatment discontinuation in the mother seems to outweigh the risk of treatment to the fetus, as maternal depression may negatively affect the child’s development; thus, women who are treated with SSRIs/SNRIs can continue to take during pregnancy the minimal effective dose.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Funding

This manuscript has not received funding.