Antidepressants During Pregnancy: Weighing the Risks of Medication vs. Untreated Depression

Table of Contents

• Key Points
• Introduction: The Big Question
• What Medical Guidelines Say
• Birth Defects: Understanding the Numbers
• A Closer Look: The Author's Systematic Review and Meta-Analysis
• Child Development: What Long-Term Studies Show
• The New Study: Nulman and Colleagues' Findings
• Earlier Evidence from the Motherisk Program
• Clinical Implications: What This Means for Doctors and Patients
• Study Limitations
• Recommendations for Patients
• Frequently Asked Questions
• Source Information

Key Points

• Antidepressant use during pregnancy has not been shown to raise birth defect risk above the 2%–3% general population baseline, except paroxetine.
• A meta-analysis found exposed infants had gestational age about 3 days shorter and birth weight 75 grams lower, but within normal ranges.
• Long-term studies found no significant negative impact on child development from prenatal antidepressant exposure.
• Untreated depression during pregnancy is linked to fetal, cognitive, and behavioral problems in children, plus higher postpartum depression risk.
• Decision-making requires individualized weighing of medication risks versus untreated depression risks, with informed consent and doctor discussion.

Introduction: The Big Question

For millions of women who take antidepressants, discovering they are pregnant raises an immediate and deeply personal question: Should I keep taking this medication, or is it safer for my baby if I stop?

The answer is not simple. As Dr. Meir Steiner of McMaster University in Hamilton, Ontario, explains in this editorial, the question of whether treating maternal depression during pregnancy is better or worse for the child than leaving the depression untreated remains largely unanswered.

Steiner emphasizes that this is not just a theoretical debate. Depression, anxiety, and stress during pregnancy—especially in the early stages—are known to have harmful effects on the developing baby. Yet many women and their doctors are also concerned about the potential risks of antidepressant exposure. This creates a genuine dilemma that requires careful, individualized decision-making.

What Medical Guidelines Say

Over the past five years, several major medical organizations have published guidelines addressing this very question. These include:

• The American Psychiatric Association and the American College of Obstetricians and Gynecologists (2009)
• Great Britain's National Institute for Health and Clinical Excellence (NICE, 2007)
• The Scottish Intercollegiate Guidelines Network (SIGN, 2012)
• The Black Dog Institute of Australia (2012)

All of these guidelines reach a similar conclusion. They end with a cautionary statement that the decision to use medication during pregnancy must carefully take into account any possible risk associated with using antidepressants at this time.

That may sound cautious, but it reflects a genuine uncertainty in the medical community. The evidence is not yet strong enough to give a definitive answer in either direction.

Birth Defects: Understanding the Numbers

Much of the existing research on antidepressants during pregnancy has focused on two concerns: the risk of birth defects (malformations) and the risk of a temporary withdrawal-like condition in newborns called neonatal discontinuation syndrome (also known as neonatal withdrawal or adaptation syndrome).

Steiner points out a key limitation in this research. Much of the monitoring is based on retrospective case-control surveillance, a method in which researchers look back at past cases. This approach has well-known limitations, including difficulty in accurately recalling medication use and potential biases in which cases get reported.

So what do the numbers actually say? According to the Metropolitan Atlanta Congenital Defects Program, the risk of major structural or genetic birth defects in the United States is approximately 3% of all births. This is the baseline risk that every pregnancy carries, regardless of medication use.

The encouraging news, Steiner reports, is that:

• There is no report suggesting that antidepressant use during pregnancy increases the risk of birth defects above the general population risk of 2%–3%
• There is no evidence that antidepressants cause organ-specific defects

There is, however, one important exception. Some reports suggest that the antidepressant paroxetine (brand name Paxil) used early in pregnancy is associated with an increased risk of atrium septum defects—a type of hole in the wall between the upper chambers of the heart.

A Closer Look: The Author's Systematic Review and Meta-Analysis

Steiner and his colleagues recently completed a large systematic review and meta-analysis—a type of study that combines and analyzes the results of many previous studies—looking at pregnancy and delivery outcomes after antidepressant exposure. This work was authored by Ross et al. and published in the Archives of General Psychiatry.

Specifically, the review focused on three outcomes among infants exposed to antidepressants in the womb:

1. Gestational age (how long the baby was in the womb)
2. Birth weight
3. APGAR scores (a quick assessment of a newborn's health, measured at 1 and 5 minutes after birth)

The results showed statistically significant associations for all three outcomes. But here is where it is important to interpret the numbers carefully. The differences were remarkably small:

• Gestational age: approximately 3 days shorter in the exposed group
• Birth weight: 75 grams lower (about 2.6 ounces, or roughly the weight of a small apple)
• APGAR scores at 1 and 5 minutes: a difference of less than half a point

Critically, the values in the exposed group typically fell within the normal range. In other words, while the differences were statistically measurable, they were not large enough to be considered clinically significant in a way that would alarm parents or pediatricians.

Child Development: What Long-Term Studies Show

Fewer studies have looked at the longer-term picture: what happens to children's development after exposure to antidepressants before birth. The handful of studies that do exist have examined cognitive and behavioral functioning in preschoolers, as well as long-term follow-up into adolescence and adulthood.

According to Steiner, none of these studies suggests any significant negative impact from prenatal antidepressant exposure. Two major studies support this view:

• The Danish National Birth Cohort (Pedersen et al., 2010) found no delays in normal milestone development at 6 and 19 months of age
• The Norwegian Mother and Child Cohort Study (Nordeng et al., 2012) reported similarly reassuring findings

But here is the other side of the coin. Steiner stresses that there is ample evidence that anxiety, depression, and particularly stress during pregnancy—especially early in gestation—can have adverse effects on:

• Fetal maturation
• Cognitive performance during infancy
• Learning and memory in 6-to-8-year-old children

This creates a paradox: the very condition being treated can itself cause harm if left untreated.

The New Study: Nulman and Colleagues' Findings

In this issue of the American Journal of Psychiatry, Nulman and colleagues, from the Motherisk Program at the Hospital for Sick Children in Toronto, present new data on the long-term neurodevelopment of children exposed to two types of antidepressants—venlafaxine (a serotonin-norepinephrine reuptake inhibitor, or SNRI) and selective serotonin reuptake inhibitors (SSRIs)—compared to children of mothers with untreated depression.

The findings are striking:

• The results failed to show any effect of antidepressant medication on children's intellectual or behavioral outcomes
• Instead, untreated depression was associated with a higher risk for the mother developing postpartum depression
• Prenatal and childhood exposure to maternal depression was associated with behavioral problems in the offspring and may increase the risk for long-term psychopathology (mental health disorders)

In plain terms: the depression itself appears to be the greater threat to a child's long-term mental health, not the medication used to treat it.

Earlier Evidence from the Motherisk Program

This is not the first time this research group has reported such findings. Ten years earlier, in 2002, the same Motherisk group published a prospective, controlled study with remarkably similar results.

In that earlier study, Nulman and colleagues found that exposure to tricyclic antidepressants or fluoxetine (brand name Prozac) throughout gestation was:

• Not associated with poor cognition
• Not associated with delays in language development
• Not associated with temperament problems in preschool and early-school children

Meanwhile, maternal depression was associated with lower cognitive and language achievement in the children. The consistency of these findings over a decade, covering both older and newer antidepressants, provides growing reassurance about medication safety relative to the risks of untreated illness.

Clinical Implications: What This Means for Doctors and Patients

So does this mean every pregnant woman with depression should be prescribed an antidepressant? Not exactly. Steiner offers several important caveats.

Regardless of the encouraging evidence, health care providers should keep in mind that the indication for prescribing antidepressants during pregnancy must be compelling. This means:

1. It is crucial to establish a proper psychiatric diagnosis (formally called an Axis I diagnosis) before starting or continuing treatment
2. It is important to assess the degree of distress and the burden of illness the pregnant woman is actually experiencing
3. It is paramount to have a frank discussion with the patient—and whenever possible, with her partner present—about the pros and cons of using antidepressants during pregnancy, based on the most recent available evidence
4. The clinician must obtain the patient's, or the couple's, informed consent

In other words, antidepressants are not to be prescribed casually during pregnancy, but they should not be withheld when genuinely needed. The decision requires individualized, shared decision-making.

Study Limitations

This editorial itself is not a clinical trial, and it is important to understand its limitations:

• The conclusions draw on the existing body of research, much of which relies on observational data rather than randomized controlled trials
• Retrospective case-control surveillance, commonly used to monitor birth defects, has inherent limitations, including recall bias and reporting bias
• The author notes that the question of whether antidepressant treatment is better or worse than untreated maternal depression is still mostly unanswered, meaning that even the reassuring findings must be considered within the context of ongoing scientific uncertainty

The truth is that randomized controlled trials of antidepressants during pregnancy would raise significant ethical concerns, so researchers must rely on large observational cohorts and meta-analyses to piece together the picture.

Recommendations for Patients

If you are pregnant or planning to become pregnant and are taking an antidepressant—or if you are experiencing symptoms of depression during pregnancy—here is what the current evidence suggests:

1. Do not stop or change your medication without speaking to your doctor first. Abruptly stopping can trigger withdrawal symptoms and a relapse of depression, which carries its own risks.
2. Have an informed conversation with your health care provider. Discuss the specific antidepressant you are taking, the dose, and your personal history of depression. Paroxetine (Paxil) may carry a slightly higher risk of a specific heart defect, so alternative options may be worth discussing.
3. Know the baseline risk. The general population risk of major birth defects is about 2%–3%, and studies to date have not shown antidepressants to raise that risk overall.
4. Understand that untreated depression matters. Depression, anxiety, and stress during pregnancy are linked to problems in fetal development, cognitive performance in infancy, and learning and memory issues in childhood.
5. Take untreated depression seriously. Untreated depression is associated with a higher risk of postpartum depression, and children exposed to maternal depression are at higher risk for behavioral problems and long-term mental health difficulties.
6. Consider the whole picture. The decision is not simply "medication vs. no medication." It is about weighing the risks of treatment against the risks of untreated illness—for both you and your child.

Every pregnancy is unique, and so is every woman's mental health history. The best decision will be one made collaboratively between you and a trusted health care provider, with your partner involved whenever possible.

Frequently Asked Questions

Should I stop taking my antidepressant if I find out I am pregnant?

Do not stop or change your medication without speaking to your doctor first. Abruptly stopping can trigger withdrawal symptoms and a relapse of depression, which carries its own risks. Have an informed conversation with your health care provider about the specific antidepressant, dose, and your personal history.

Do antidepressants during pregnancy increase the risk of birth defects?

Studies to date have not shown antidepressant use to raise the overall risk of major birth defects above the general population risk of about 2%–3%. There is one exception: some reports link paroxetine (Paxil) used early in pregnancy with a slightly higher risk of a specific heart defect. Discuss alternatives with your doctor.

What are the risks of untreated depression during pregnancy?

Untreated depression, anxiety, and stress during pregnancy can harm fetal development, cognitive performance in infancy, and learning and memory in childhood. Untreated depression also increases the mother's risk of postpartum depression and children's risk of behavioral problems and long-term mental health difficulties.

Do antidepressants affect the baby's birth weight or gestational age?

A systematic review and meta-analysis found small differences: gestational age about 3 days shorter and birth weight 75 grams lower in exposed infants. These values typically fell within the normal range, so the differences were statistically measurable but not clinically significant enough to alarm parents or pediatricians.

Do antidepressants affect a child's long-term development?

Long-term studies, including the Danish National Birth Cohort and the Norwegian Mother and Child Cohort Study, found no significant negative impact on development. A new study by Nulman and colleagues found no effect on intellectual or behavioral outcomes from medication, but untreated maternal depression was linked to behavioral problems.

Is it better to take antidepressants or leave depression untreated during pregnancy?

The editorial states this question is largely unanswered, but evidence suggests the depression itself appears to be the greater threat to a child's long-term mental health than the medication. The decision requires weighing risks on both sides and making an individualized choice with your doctor and partner.

How should I decide whether to take antidepressants during pregnancy?

Discuss with your doctor: establish a proper psychiatric diagnosis, assess the degree of distress, and have a frank discussion about pros and cons based on recent evidence. Involve your partner if possible, and give informed consent. Antidepressants should not be prescribed casually, but not withheld when genuinely needed.

Should I get a second opinion about continuing antidepressants during pregnancy?

A pregnant woman taking antidepressants—or considering them for depression—should seek a second opinion if she or her doctor is unsure whether to continue, stop, or switch medication. The decision must balance small, mostly normal-range differences in birth outcomes (about 3 days shorter gestation, 75 grams lower birth weight) against real risks of untreated depression, including higher postpartum depression rates and child behavioral problems. Because paroxetine may carry a slightly higher risk of a specific heart defect, a second opinion can help explore alternatives. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

This patient-friendly article is based on the following peer-reviewed editorial:

Title: "Prenatal Exposure to Antidepressants: How Safe Are They?"

Publication: American Journal of Psychiatry, 169(11):1130–1132, November 2012

DOI: 10.1176/appi.ajp.2012.12081126

Key studies referenced in this editorial:

• Yonkers KA, et al. (2009). The management of depression during pregnancy: APA/ACOG report. General Hospital Psychiatry, 31:403–413.
• NICE (2007). Antenatal and Postnatal Mental Health: The NICE Guideline.
• SIGN (2012). Management of Perinatal Mood Disorders.
• Black Dog Institute (2012). Safety of Antidepressants in Pregnancy and Breastfeeding.
• CDC (2008). Update on overall prevalence of major birth defects—Atlanta, Georgia, 1978–2005. MMWR, 57:1–5.
• Bérard A, et al. (2007). First trimester exposure to paroxetine and risk of cardiac malformations. Birth Defects Research, 80:18–27.
• Bakker MK, et al. (2010). First-trimester use of paroxetine and congenital heart defects. Birth Defects Research, 88:94–100.
• El Marroun H, et al. (2012). Maternal SSRI use, fetal growth, and adverse birth outcomes. Archives of General Psychiatry, 69:706–714.
• Occhiogrosso M, et al. (2012). Persistent pulmonary hypertension of the newborn and SSRIs. American Journal of Psychiatry, 169:134–140.
• Ross LE, et al. (in press). Effects of prenatal antidepressant treatment on pregnancy and delivery outcomes: a systematic review and meta-analysis. Archives of General Psychiatry.
• Pedersen LH, et al. (2010). Fetal exposure to antidepressants and normal milestone development at 6 and 19 months. Pediatrics, 125:e600–e608.
• Nordeng H, et al. (2012). Pregnancy outcome after exposure to antidepressants. Journal of Clinical Psychopharmacology, 32:186–194.
• Sandman CA, et al. (2012). Exposure to prenatal psychobiological stress. Neuroendocrinology, 95:8–21.
• Buss C, et al. (2011). Maternal pregnancy-specific anxiety and child executive function at 6–9 years. Stress, 14:665–676.
• Nulman I, et al. (2012). Neurodevelopment of children following prenatal exposure to venlafaxine, SSRIs, or untreated maternal depression. American Journal of Psychiatry, 169:1165–1174.
• Nulman I, et al. (2002). Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life. American Journal of Psychiatry, 159:1889–1895.

Conflict of interest disclosure: Dr. Steiner has served as a consultant for AstraZeneca, Azevan, Bayer Schering, Lundbeck, Servier, and Wyeth; has received grants or research support from AstraZeneca, the Canadian Institutes of Health Research, GlaxoSmithKline, Lundbeck, Pfizer, and Wyeth; and has received honoraria from AstraZeneca, Azevan, Ortho-McNeil, and the Society for Women's Health Research.

This patient-friendly article is based on peer-reviewed research and is intended for educational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.