Antidepressants and Pregnancy: Finding a Healthy Balance

There are risks to both taking antidepressants and not treating depression during pregnancy.

Study results show that depression affects as many as 23% of pregnant women.^1-3 Mild depression can usually be managed with psychotherapy, but pharmacotherapy is recommended for women with severe or highly relapsing depression.^3,4 The truly questionable area is moderate to severe depression that has not responded adequately to nonpharmacologic treatments.^1,4

During pregnancy, there are risks to both taking antidepressants and not treating depression during pregnancy. Regarding this issue, there is a lack of consensus among the medical community. ^3,5 Because randomized trials in pregnant women are unethical, available data on antidepressant use during pregnancy are from retrospective analyses, which show correlation rather than causation.² Although antidepressants carry warnings regarding perinatal complications, particularly cardiovascular malformations, most associations have been weak and/or inconsistent and may also be linked with maternal depression.^6,7

Pregnant women are likely to discontinue psychiatric medications, even when told continuation is appropriate.^1,8 The most important factor in the decision whether to stop taking antidepressants is the order in which a woman receives risk/benefit information—whichever she hears first has the greatest effect.⁸

Maternal Depression and Relapse Risk

Women who suffer from depression are more likely to have suboptimal prenatal care, poor nutrition, or substance abuse problems.¹ Untreated depression is also linked to poor neonatal outcomes, such as low birth weight, prematurity, lower Apgar scores, poor growth, irritability, fewer facial expressions, less active and attentive babies, and a higher maternal suicide risk.^1,4,9

Depression relapse during pregnancy is a notable risk.^3,10 Although many women stop taking antidepressants during their first trimester, 68% relapse and have to restart during pregnancy—half during the first trimester alone. Those who relapse often have a history of previous relapses, suffer longer duration of depression, are younger, or have another psychiatric illness (eg, anxiety or eating disorders).¹⁰

Birth Complications

Paroxetine, fluoxetine, and venlafaxine may cause postnatal adaptation syndrome (PNAS),^10,11 which has the strongest link to antidepressants and occurs in up to 30% of babies exposed to selective serotonin reuptake inhibitors (SSRIs)during the third trimester.¹¹ PNAS symptoms include irritability, hypertonia, jitteriness, and trouble feeding; it occurs shortly after birth, but resolves within days or weeks.¹¹

Antidepressant use also slightly increases the likelihood of preterm birth (usually defined as birth at less than 37 weeks) compared with the general population; however, the rate is similar in unmedicated women suffering from severe depression.^2,3,12 Although thirdtrimester SSRI use shows a statistically significant decrease in birth weight, Apgar scores, and gestational age, the absolute differences are small (approximately 3 days’ shorter gestation, 75-g lower weight, and less than a half-point difference on 1- and 5-minute Apgar scores) and are often still within normal ranges.² Apgar scores of 7 or higher are normal¹³; mean scores with antidepressant exposure are 7.52 at 1 minute and 8.65 at 5 minutes.² A 2013 study also showed a slight increase in children born small for their gestational age (below the 10th percentile) to mothers taking SSRIs and newer antidepressants, but no link with older antidepressants or untreated depression.¹⁴

Use of serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and SSRIs between 10 and 20 gestational weeks showed increased preeclampsia compared with untreated depression. Women not on antidepressants (depressed or not) had a 2.4% greater chance of preeclampsia compared with 3.3% on SSRI monotherapy, 4.5% on SSRI polytherapy, 5.6% on SNRI monotherapy, and 9.6% taking TCAs.¹⁵

The FDA Pediatric Advisory Subcommittee is recommending a new warning for SSRIs and SRNIs about the potential for withdrawal syndrome (eg, agitation, irritability, difficulty feeding, sleep problems) in newborns. Respiratory distress, cyanosis, apnea, seizures, hypertonia, hyperreflexia, and tremor have also been reported. The committee did not wish to scare women away from treatment based on what they see as preliminary information, but they are recommending tapering off SSRIs and SNRIs during the last trimester, with a goal of stopping about 7 to 10 days before delivery to minimize withdrawal risk.¹⁶

Neonatal Risks

Paroxetine and fluoxetine may cause birth defects, particularly cardiovascular malformations^5,10,17; however, study results are inconsistent, the increases seen were small, and these defects are uncommon.¹⁷ There is currently no evidence that other antidepressants can cause congenital or major malformations.¹⁷

Newborn persistent pulmonary hypertension (PPHN) is a rare (up to 1.2%) but potentially fatal condition, usually seen in full-term or late children. The results of several studies have been inconsistent: from no effect to a 6% increase of PPHN with antidepressant use. A recent, large (>1 million women) analysis showed an occurrence of PPHN in 1.9% of births to women who used SSRIs early in pregnancy and in 3% of births when used late in pregnancy (after week 20).¹⁸

Autism has increased in recent decades, which may be from changing diagnostic standards, greater awareness, or environmental issues.⁷ Study results regarding the effects of antidepressant use and the occurrence of autism are very mixed, but seem to point to an increased risk. One study’s results showed a higher risk for autism (specific to disorders without intellectual disability; no increase in autism with intellectual disability was seen), stating that up to 0.6% of cases of autism could be explained by maternal antidepressant use.¹⁹ Data from another report showed an increase (up to 5.1%) in autism with exposure to SSRIs during gestation,^5,7 with first-trimester use carrying the highest risk.⁷ The results from 2 more studies linked prolonged SSRI use to lower language competency at age 3 years and an increase in hyperactivity, but not autism.⁵ The effects of long-term antidepressant use in pregnancy are unclear, however, since many of the reported chronic events are more common in mothers who suffer from depression.

Other Options

Psychotherapy is recommended, but it may take 12 or more weeks before improvement is seen.²⁰ Coping mechanisms that patients found helpful include focusing on their depression (acknowledging that coping strategies were needed), participating in social activities, and having professional support.²¹

About 11% of people with depression use complementary or alternative therapy.²⁰ Yoga during pregnancy is associated with a significant decrease in depression, with no safety issues identified.²² Other successful approaches include depression-specific acupuncture, massage, light therapy, and exercise.^20,23 Omega-3 fatty acids have questionable efficacy: although 2 studies showed improved depressive scores, another did not.²⁰

Conclusion

In the past 20 years, antidepressant use during pregnancy has increased: as many as 14% of women take antidepressants at some time during pregnancy.^3,5,6,12 Statistically significant changes were seen among women on antidepressants with respect to preterm delivery, gestational age, and Apgar scores; however, these differences were typically within normal limits, making difficult the decision on whether risks outweigh benefits.²

Stopping the use of SSRIs abruptly is not recommended; tapering is the preferred method for women who are pregnant or are planning to become pregnant. Nonpharmacologic options such as counseling, exercise, acupuncture, and light therapy are encouraged.⁵ The final decision lies with the well-informed mother and her physician.⁴

Debra Freiheit has been a practicing pharmacist and human services professional for over 25 years. Specializing in medical information, she has compiled a broad spectrum of experience obtained through research for companies including Cerner and PPD, Inc. With an emphasis on clear and concise information transfer, she has built a career communicating data to medical professionals and patients. Education and knowledge have been the motivation behind her career rich in caregiving through research. Debra’s current project involves the creation of a multinational database of drug information.

References

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