Safety of Newer Antidepressants in Pregnancy

Cynthia M. Way, B.Sc.Pharm.


Pharmacotherapy. 2007;27(4):546-552. 

In This Article

Abstract and Introduction


Pharmacotherapy for depression is often necessary during pregnancy. The information available about use of the newer antidepressants in pregnant women is limited by trial design and lack of long-term follow-up of exposed infants. Selective serotonin reuptake inhibitors (SSRIs) are not generally thought to be major teratogens. Some recent studies, however, have suggested that paroxetine may be associated with a small increase in risk of congenital abnormalities, particularly cardiac defects. Data on the effect of SSRIs on the incidence of preterm birth, spontaneous abortion, and fetal death are conflicting. Third-trimester exposure to newer antidepressants, including SSRIs and serotonin-norepinephrine reuptake inhibitors (e.g., venlafaxine), has been associated with a poor neonatal adaptation syndrome. In addition, SSRI use may be associated with an increased risk of persistent pulmonary hypertension of the newborn. Preliminary evidence suggests that SSRI exposure in utero does not have significant long-term effects on cognition or behavior. Based on limited information, mirtazapine, bupropion, and venlafaxine do not appear to be major teratogens. Little or no information is available on duloxetine.


Up to 20% of pregnant women experience clinical depression.[1,2] Depression during pregnancy may have adverse consequences for the woman and her baby and has been associated with preterm delivery, low birth weight, preeclampsia, postpartum depression, and possibly spontaneous abortion.[3] In addition, pregnant women with depression are less likely to attend regular obstetric visits and may have lower than normal weight gain, may lack compliance with prenatal care, and may be more likely to smoke, drink alcohol, or use cocaine.[3] Also, these women are subject to the same adverse consequences of depression as are non-pregnant women, including social withdrawal and even suicide.[3]

Treatment options for depression include psychotherapy, bright-light therapy, antidepressant drugs, and electroconvulsive therapy.[2] The optimal treatment for depression during pregnancy varies from woman to woman, but pharmacotherapy is often necessary.[2] A study of 201 women with a history of major depressive disorder before pregnancy found that 68% of those who discontinued treatment relapsed during pregnancy compared with 26% of those who continued treatment.[4] Affected women and their clinicians may be concerned about the effects of drug treatment on the fetus and the neonate. Information is available on the safety of antidepressant use during pregnancy but is limited by the small size of most trials and by trial designs that often did not use mothers with depression as control subjects and could not, for ethical reasons, be randomized and double blinded. Long-term follow-up of exposed infants also has generally been insufficient.

The effects of antidepressants on pregnancy outcome can be categorized into five domains: physical malformations (teratogenicity); intrauterine death, spontaneous abortion, or preterm delivery; growth impairment; neonatal toxicity; and behavioral teratogenicity (i.e., long-term effects on neurocognitive development).


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