Psychotropic drugs in pregnancy

Psychotropic drugs in pregnancy

Introduction

Approximately 3.0% of all pregnant women take psychotropic drugs during pregnancy (Molenaar et al., 2020) and the pre- and postpartum periods are widely considered as a period of increased vulnerability to psychiatric disorders (Bonari et al., 2004).

For every pregnancy, the baseline risk of a major congenital malformation is 1% to 3% of the population (McElhatton, 2013). All psychotropic drugs pass the placenta, meaning all fetuses are exposed to maternal psychotropics (Altshuler et al., 1996). The possible risks of psychotropic drug use during the first trimester of pregnancy include spontaneous abortion and malformations. In later pregnancy, risks of psychotropic medication might include pregnancy and perinatal complications such as low birth weight, prematurity, poor neonatal adaptation (feeding difficulties, irritability, tremor) and the possibility of longer-term neurobehavioral effects (Kohen, 2004).

Data on the effects of psychotropic medication are limited and sometimes conflicting, especially as the effect of underlying depression on maternal and fetal outcomes is often underestimated. There is an increasing body of evidence-based information indicating that it may be more harmful to both the mother and her baby if she is not treated appropriately when suffering from a severe psychiatric disorder (Bonari et al., 2004; Niethe & Whitfield, 2018).

Pregnant women should be involved in discussions about the risks and benefits of using – or not — pharmacological treatment. Ideally, decision making should occur before pregnancy, because many pregnancies are unplanned. If possible, drugs that are contraindicated during pregnancy (carbamazepine and especially valproate) should be avoided in women in childbearing age. In the case that these drugs are prescribed, women should be carefully informed about their teratogenic potential, and this discussion recorded in the medical record (NICE, 2018).

Principles of psychotropic medication use during pregnancy  (adapted from  Kohen, 2004)

A single medication at a higher dose is favoured over multiple medications

Medications with fewer metabolites are preferred

Higher protein binding decreases placental passage

Changing medications increases the exposure to the baby

Dose increase is frequently required in the third trimester due to increased blood volume, which changes rapidly post-partum and may require dose reduction

If a woman is being treated successfully with psychotropic medication before pregnancy, the same treatment should continue throughout pregnancy if there is no major risk of malformation

If pregnancy is planned and mental health is stable with a low risk of relapse, discontinuing psychotropic medication may be considered

Folic acid supplements are recommended in most country guidelines for all pregnant women because of the associated reduction in neural tube defects.

Specific ultrasound of the fetus should be performed in women on psychotropics to exclude major malformations, and joint working with antenatal care and monitoring programs are recommended.

Antidepressants

Selective serotonin reuptake inhibitors (SSRIs)

SSRIs are widely prescribed including during pregnancy, and are thought to be relatively safe (Anderson et al., 2020), there are some reports of morphological teratogenicity. A small increased absolute risk of rare defects such as omphalocele, anencephaly, craniosynostosis, cystic kidney and congenital heart defects has been reported. However, specific patterns of congenital malformations have not been demonstrated with SSRIs across studies (Byatt et al., 2013). Paroxetine is most controversial SSRI and has a specific connection to an increased risk of congenital malformations. First-trimester paroxetine exposure is associated with an increased prevalence of combined cardiac defects (Hinds et al., 2011).

A possible increase of spontaneous abortions, earlier delivery, lower birth weight and low APGAR scores, hypoglycemia and hyperbilirubinemia have been noted on connection with use of SSRIs during pregnancy (Chang et al., 2020; Xing et al., 2020).

Of all infants exposed to an SSRI in utero, around 30% develop symptoms of poor neonatal adaptation syndrome (PNAS) such as hypotonia, hypothermia, respiratory depression, cyanosis, arrhythmias and decrease sucking reflex (Grigoriadis & Peer, 2019). Some studies described an increased incidence of PNAS after exposure to paroxetine and fluoxetine compared to other SSRIs (Kieviet et al., 2013).

There is conflicting evidence regarding an elevated risk of persistent pulmonary hypertension of the newborn (PPHN) after exposure to SSRIs. The absolute risk cannot be determined, but