SSRI use during pregnancy
Do antidepressants’ benefits outweigh the risks?
Untreated depression can have serious consequences, but many pregnant women resist taking antidepressants because they overestimate the risk of birth defects.Paroxetine in pregnancy”). Further study is needed to define the risks of teratogenesis with paroxetine compared with other antidepressants.
In a recent meta-analysis, infants exposed to SSRIs in utero showed an increased risk for prematurity (OR; 2.03) and low birth weight (OR; 2.37).15 Other studies, however, showed no differences in these risks in SSRI-exposed infants or attributed the results to untreated maternal depression or smoking.16
A Medline search across the last 20 years17 found 26 case reports, three prospective controlled cohort studies, and other records of >400 women who received fluoxetine, sertraline, or paroxetine in the third trimester. The authors found the evidence “ambiguous” as to the cause of adverse events and concluded that the risk of not treating major depression with adequate SSRI therapy at that stage of pregnancy “most likely” outweighs the risk of harm to infants.
Transient neonatal complications. Thirty percent of neonates exposed to SSRIs in the third trimester experience transient adaptation problems, which peak 48 hours after birth18 (Table 3). Symptoms may include initial lack of crying, increased muscle tonus, flush, irritability, jitteriness, hypothermia, abnormal breathing, and disrupted sleep and motor activity.2,19,20
Transient neonatal symptoms from SSRI exposure are thought to be a serotonin withdrawal syndrome or serotonin overstimulation.21 The syndrome is usually mild, self-limited, and requires only supportive treatments. All antidepressants’ labels warn of these effects.
Neonatal SSRI withdrawal: Symptoms, causes, and treatment
Initial lack of crying
Increased muscle tonus
Abnormal breathing pattern
Disrupted sleep and motor activity
Hypotheses of cause
Serotonin overstimulation or withdrawal
Pulmonary hypertension. An increased risk of persistent pulmonary hypertension of the newborn (PPHN) has been shown in infants exposed to SSRIs after 20 weeks’ gestation. A retrospective case-control study concluded that the absolute risk of PPHN with SSRIs is relatively low (6 to 12 cases per 1,000 pregnancies).22
Recommendation. Some authors have recommended tapering antidepressants in the third trimester, but the risk of postpartum depression appears to outweigh any potential benefit from discontinuation. Because birth timing is unpredictable, some women whose antidepressants are tapered off could be without medication for a long time.
Thus, we recommend:
- continuing SSRIs during late pregnancy
- monitoring the newborn for 48 hours for transient neonatal adaptation symptoms or PPHN.2,17,18
Long-term effects of SSRI exposure
Do SSRIs during pregnancy have long-term effects on infants’ neurodevelopment? Study results are mixed. For example:
- A prospective, controlled, cohort trial found no adverse effects on IQ, language, or behavioral development in children ages 15 months to 6 years whose mothers took tricyclic antidepressants (N=46) or fluoxetine (N=40) during pregnancy, compared with 36 unexposed controls.23
- Another prospective study showed lower Bayley Psychomotor Developmental Index scores in 31 SSRI-exposed infants compared with 13 infants born to depressed mothers not on antidepressants. Reduced body control, coordination, and fine motor skills might suggest possible subtle effects of SSRIs on motor development in exposed infants, the authors concluded.24
Case continued: A healthy delivery
Ms. P’s depression improves a few weeks after she restarts an SSRI. She delivers a healthy term baby with Apgar score of 7. The baby initially does not cry, awakens easily, and shows mild irritability. His mother’s SSRI use, her severe depression during part of the pregnancy, or some other factor may have caused his mild neonatal complications.
Nursing staff carefully observe the infant for 2 days in the newborn nursery, and his irritability fades away. Ms. P decides to continue taking antidepressants to care for herself and the baby.
Weighing treatment options
For each woman with a history of depression who is pregnant or intends to conceive, we recommend a risk-benefit analysis of her depression severity and need for an antidepressant:
Mild depression (BDI <20 and no history of recurrent depressive episodes, hospitalization, suicidality, weight loss, or inability to function). Consider treating depression without medication. Interpersonal psychotherapy and morning light therapy have improved antepartum depression in small trials.25,26
Moderate to severe depression (history of recurrent depressive episodes, hospitalization, or suicidality). Strongly consider medication. If your patient is taking an SSRI, counsel her about:
- the 70% risk of depression relapse if she stops the medication, even for the first trimester
- risks of untreated depression during pregnancy (poor self-care, preterm labor, birth complications, and increased risk for poor stress adaptations in children).
If she refuses antidepressant treatment, monitor her for suicidal tendencies, deteriorating social function, psychosis, and inability to comply with prenatal care during the pregnancy and postpartum.
Choosing an SSRI. No one SSRI is the safest choice for all women, especially when data on breast-feeding come into play.
- Fluoxetine has been studied more than other SSRIs during pregnancy; most evidence is reassuring, except for transient neonatal complications. With its long half-life, fluoxetine is not recommended during breastfeeding because it may accumulate in infant sera.
- Sertraline has shown low umbilical cord to maternal serum ratios in small samples and has reassuring breast-feeding data.
- Citalopram, compared with sertraline, has been studied more in pregnancy but has a higher fetal-to-maternal serum ratio (as does escitalopram). These SSRIs are usually second-line for starting a new antidepressant during pregnancy but could be first-line if they have worked well for a patient or she has had adverse effects with fluoxetine or sertraline.
You may need to increase SSRI dosages as pregnancy progresses. Increased metabolism and weight gain during pregnancy can lower SSRI serum levels, allowing depressive symptoms to re-emerge in the third trimester. Counsel the patient to continue taking the antidepressant for at least 12 months postpartum, then re-evaluate the need for medication based on her history.
Paroxetine precautions. If your patient is taking paroxetine and wishes to become pregnant, consider switching to another SSRI (using a slow cross-taper) unless paroxetine has been the only effective medication (Table 4). When discussing risks of any SSRI, explain that the baseline risk for congenital malformations is 3%. Paroxetine might increase this risk by 1% and other SSRIs by less.
If a woman becomes pregnant while taking paroxetine, often the time when cardiac defects occur is passed or will be before you slowly taper the medication to avoid withdrawal. If the patient’s depression has been severe, the risk of shifting her to an untested SSRI is probably higher than the possible 1% increased risk of fetal malformation. If she has taken paroxetine during the first-trimester, refer for ultrasound to monitor for cardiac anomalies.
Recommendations for managing paroxetine risk during pregnancy
Taking paroxetine and planning pregnancy
Advise of possible 1% increase in risk of fetal malformation
Switch to another SSRI unless paroxetine has been the only successful therapy for depression
If stopping paroxetine, slowly taper to avoid withdrawal symptoms
Taking paroxetine and is pregnant
Advise of possible 1% increase in risk of fetal malformation
Continue paroxetine; a slow taper probably could not be completed before the first-trimester period associated with increased risk of fetal cardiac defects
If any paroxetine exposure in first trimester, order ultrasound to monitor for fetal malformations
- California Teratogen Information Service (CTIS). Pediatric department, University of California San Diego Medical Center. www.otispregnancy.org/ctis.html
- MGH Center for Women’s Mental Health, Massachusetts General Hospital. Psychiatric disorders during pregnancy and postpartum. www.womensmentalhealth.com
- MOTHERISK Web site. Teratogen information and updates on reproductive risk research. The Hospital for Sick Children, University of Toronto. www.motherisk.org
Drug brand names
- Citalopram • Celexa
- Escitalopram • Lexapro
- Fluoxetine • Prozac
- Paroxetine • Paxil
- Sertraline • Zoloft
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
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