Avoid Paxil in Pregnancy, ACOG Committee Advises

WASHINGTON, Nov. 30 -- The antidepressant Paxil (paroxetine) may cause fetal cardiac malformations, and the drug should be shunned if possible in pregnancy, recommended an advisory committee of the American College of Obstetricians and Gynecologists.

"At this time, paroxetine use among pregnant women and women planning pregnancy should be avoided, if possible," wrote members of the ACOG committee on obstetric practice in the December issue of Obstetrics & Gynecology.

"Fetal echocardiography should be considered for women who were exposed to paroxetine in early pregnancy," they added. "Because abrupt discontinuation of paroxetine has been associated with withdrawal symptoms, discontinuation of this agent should occur according to the product's prescribing information."

Although several previous studies have failed to find a link between SSRI use in pregnancy and major congenital malformations, GlaxoSmithKline, the maker of Paxil, has revealed that unpublished reports from a U.S. insurance-claims database and a Swedish national registry have suggested a possible link between Paxil used in the first trimester and increased risk of atrial and ventricular septal defects, pointed out the committee.

An estimated 2% to 3% of women use Paxil or another selective serotonin reuptake inhibitor (SSRI) during pregnancy, the authors noted.

In the Swedish report, women who received Paxil in early pregnancy had about a twofold increased risk for having an infant with a cardiac defect compared to the entire national registry population.

In the U.S. study, children born to women who took Paxil in the first trimester had a 1.5-fold increased risk for cardiac malformations, and a 1.8-fold increased risk for congenital malformations overall compared with children of women who took other antidepressants, according to an FDA advisory issued in December 2005.

In both instances, the findings were restricted to Paxil, and not to other SSRIs.

The findings prompted a change in Paxil's labeling from Pregnancy Category C (drugs with a teratogenic effect in animal studies that have not been adequately studied in humans) to Category D (drugs that have been found to have harmful effects on human fetuses).

The committee members suggested that the decision to use or discontinue SSRIs during pregnancy is a difficult one, citing studies showing on the one hand that women who discontinued antidepressants during pregnancy had a fivefold greater risk for depression relapse than women who continued taking the drugs, and on the other hand a large case-control study that found a six-fold increase in the risk of persistent pulmonary hypertension for newborns whose mothers used SSRIs after 20 weeks of gestation.

"The potential risk of SSRI use throughout pregnancy must be considered in the context of the risk of relapse of depression if maintenance treatment is discontinued," they wrote. "Untreated depression may increase the risk of low weight gain, sexually transmitted diseases, and alcohol and substance abuse, all of which have maternal and fetal health implications."

The committee members recommended an individualized approach to treating pregnant women or women who are planning pregnancy with all SSRIs and/or selective norepinephrine reuptake inhibitors.

"Decisions about treatment of depression should incorporate the clinical expertise of the mental health clinician and obstetrician, and the process should actively engage the patient's values and perceptions when framing the discussion of the risks and benefits of treatment," the committee member wrote.

"Optimally, shared decision making among obstetric and mental health clinicians and women should occur before pregnancy. However, given that approximately 50% of pregnancies are not planned, preconception planning for women with depression will not always happen, and decisions regarding treatment with SSRIs will undoubtedly occur during gestation."