Risks of untreated depression in pregnancy

Risks of untreated depression

For some pregnant women, appropriate pharmacotherapy is necessary, as maternal depression has been associated with various detrimental health concerns for both the baby and the mother. Babies born to women with untreated depression are at risk of prematurity, low birth weight, and intrauterine growth restriction.^2,3 The negative consequences of untreated maternal depression might also affect childhood development. Higher impulsivity, maladaptive social interactions, and cognitive, behavioural, and emotional difficulties have been shown to occur.^4,5 The adverse outcomes of untreated maternal depression might also be detrimental to the mother. Importantly, pregnant women with depression are more at risk of developing postpartum depression and suicidality.⁶ Increased hospital admissions and pregnancy complications such as preeclampsia have also been linked to untreated maternal depression.^6,7 It has also been shown that pregnant women with depression are more likely to engage in high-risk health behaviour. Some examples include smoking, illicit substance and alcohol abuse, and poor nutrition.⁸ To prevent this behaviour, antidepressant treatment might be needed.

A large National Institutes of Health multicentre trial found that women who discontinued their antidepressant therapy relapsed significantly more frequently compared with women who maintained their antidepressant use throughout pregnancy (hazard ratio 5.0; P < .001). In that study, 68% of women who discontinued their medication had major depressive relapses compared with only 26% of women who maintained their medication, and those who discontinued their medication were 3 times more likely to be hospitalized and experience complications.⁹

Antidepressant risks

With these findings and the consequences of untreated depression, it is important to establish a risk-benefit ratio when counseling patients. The risks of untreated depression must be balanced with what is reported in the peer-reviewed literature regarding fetal exposure to antidepressants. To date, most of the more than 30 published studies, including thousands of pregnancy outcomes, reported negligible or no fetal risks. The main concern appears to be the increased risk of cardiac malformations—usually ventricular septal defects, most of which close spontaneously early in life. The increased risk was marginal and it was unknown if the spontaneously resolving minor ventricular septal defects were included in some of the studies.¹⁰ A very large Danish study reported that this apparent increase in cardiac defects occurred also among women who did not treat their depression with antidepressants, strongly suggesting that this result is probably owing to ascertainment and reporting bias, and not the anti-depressants.¹¹

Although more research needs to be conducted, the results of studies examining long-term development of children exposed in utero to selective serotonin reuptake inhibitors are reassuring, with no apparent adverse effects in the children.¹²

Health care providers should be aware that women might require increased doses of their antidepressant medications in late pregnancy owing to pharmacokinetic changes. In pregnancy, the volume of distribution and renal drug elimination increase. Additionally, the metabolic activities of CYP (cytochrome P450) 3A4 and CYP2D6, enzymes responsible for the metabolism of many selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors, have been shown to be increased.¹³ It is generally recommended that patients be treated with the minimum effective dose and monitored closely. It is important to communicate to the patient that owing to these pharmacokinetic changes, an increase in dose might be required if breakthrough symptoms occur.