Mrs. D is a 28-year-old married woman who became depressed after her first pregnancy. The depression was treated successfully with paroxetine, 20 mg/d. Before beginning treatment, she reported low mood, spent most of the day in bed, was unable to care for herself, and confessed to thoughts of harming her child.

Mrs. D presents to your clinic asking whether she should continue her selective serotonin reuptake inhibitor (SSRI) because she and her husband are thinking about having a second child. Recently, she tells you, she saw a news article suggesting that antidepressants show little benefit, and she is concerned that her baby might have a heart defect if she continues paroxetine.

Mrs. D wants to discontinue her medication, but her husband thought she should discuss doing so with you first. During this visit she takes a pregnancy test, which is positive. She wants to know what to do.

SSRI use is increasing among women during their childbearing years, a period that also carries the highest risk of depression. An estimated 7% to 23% of pregnant Practice Points

- Make decisions about the use of SSRIs in pregnancy case by case.
- Understand the risks of both untreated depression and the use of SSRIs during pregnancy.
- Sertraline, paroxetine, citalopram, and fluoxetine are the most studied SSRIs in pregnancy.
- Consider cognitive-behavioral therapy for mild depression.
women experience depression; 3.8% of pregnant women receive an SSRI.¹ SSRIs are the most commonly prescribed antidepressants during pregnancy, but their use remains controversial. There is disagreement about the maternal and neonatal risks of untreated depression and SSRI exposure.^2-10 Media reports of studies demonstrating adverse effects associated with SSRIs may generate fear among women, possibly prompting them to self-discontinue medication.

Evidence of risks and benefits

Clinicians should be aware of possible adverse effects of SSRI use and untreated depression (Table).^2-10 The available data precludes definitive associations between untreated depression and poor outcomes (Box). Studies of SSRI use during pregnancy have shown conflicting results for all potential outcomes. Absolute risk, with the exception of neonatal adaptation syndrome, is estimated to be small. Neonatal adaptation syndrome—which is characterized by jitteriness, poor muscle tone, weak cries, respiratory distress, hypoglycemia, low Apgar scores, and seizures—occurs in 15% to 30% of infants born to mothers taking SSRIs, but it is transient and resolves during the first weeks of life.

Treatment recommendations

Given the conflicting nature of the evidence, treatment plans should be individualized, weighing the risks and benefits of treatment and the patient’s beliefs and psychiatric history. Consider severity of symptoms and history, including effective therapy and history of relapse. For women with mild or moderate depression, cognitive-behavioral therapy might be an appropriate first-line therapy. However, non-pharmacotherapeutic interventions might not relieve severe depression or be available to all women. When discontinuing an SSRI before pregnancy, counsel the patient to not discontinue the medication abruptly and provide an appropriate taper schedule. See Related Resources for detailed recommendations from the American Psychiatric Association and the American College of Obstetricians and Gynecologists.

Reviewing the SSRI literature regarding pregnancy

Sertraline, paroxetine, citalopram, and fluoxetine are the most studied SSRIs during pregnancy; little information is available on escitalopram and fluvoxamine.¹¹ Prescribing preference generally is given to the medications with the most evidence; paroxetine may be an exception. In 2005, the FDA requested a change in paroxetine’s pregnancy category from C to D, indicating that adequate studies demonstrated a risk of congenital cardiac malformations.¹¹ Additional studies have been conducted, and the teratogenicity of paroxetine is debatable. A recent review reports 8 studies that suggest a malformation risk, compared with 15 studies that show no risk.¹²

The American Academy of Pediatrics considers SSRIs to be compatible with breast-feeding.¹³ The best-studied drugs include sertraline and paroxetine. Fluoxetine should be avoided when possible because a long elimination half-life can cause the drug to accumulate in the newborn, increasing the risk of irritability, hypertonia, sedation, and poor suckle.⁷

There is no best SSRI for all pregnant women. Risks and benefits, including previous treatment success and failure, should be taken into account before starting or switching therapy. Whenever possible, consider monotherapy to avoid compounding the risk of harm.

Related Resources

Yonkers KA, Wisner KL, Stewart DE, et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Gen Hosp Psychiatry. 2009;31:403-413.
MGH Center for Women’s Mental Health. www.womensmentalhealth.org.

Drug Brand Names

Citalopram • Celexa Escitalopram • Lexapro Fluoxetine • Prozac

Fluvoxamine • Luvox Paroxetine • Paxil Sertraline • Zoloft

Disclosures
Dr. Leino reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products. Dr. Ellingrod receives grant support from the National Institute of Mental Health.

SSRIs in pregnancy: What should you tell your depressed patient?