SSRIs tied to neonatal withdrawal symptoms.(News)

International reports of withdrawal symptoms in 93 newborns whose mothers had taken selective serotonin reuptake inhibitors during pregnancy raise concerns about a possible causal relationship between such symptoms and drugs in this class, according to authors of a study that identified these cases.

Nearly two-thirds (64) of these cases were seen in babies whose mothers had taken paroxetine (Paxil), which the authors concluded should not be used in pregnancy, "or, if used, should be given at the lowest effective dose."

The use of other SSRIs "should be carefully monitored and new cases promptly communicated to the pharmacovigilance systems," wrote Emilio Sanz, M.D., professor of clinical pharmacology at the University of La Laguna (Spain), and associates (Lancet 2005;365:482-7).

When asked to comment on the study, two experts on drug therapy during pregnancy disagreed with the authors' conclusions, which they said fail to balance the risks and benefits of these drugs in pregnant women with depression.

Gideon Koren, M.D., director of the Motherisk Program, a teratogen information service at the Hospital for Sick Children, Toronto, said that while the identification of these cases in an international database was commendable, he took issue with the conclusion that paroxetine should not be used in pregnancy. This recommendation is not based on an appropriate risk-benefit analysis, he said, and it does not take into account the increased risk of maternal morbidity associated with untreated maternal depression.

Moreover, the authors fail to take into account a study published last year, which found that in a large Swedish database, the association between paroxetine and these symptoms was no greater than with other SSRIs, added Dr. Koren, who said he has no financial ties to manufacturers of antidepressants.

He noted that neonatal withdrawal symptoms are self-limited and that the syndrome has "a very benign course," which also was not discussed by the authors. He and his associates at Motherisk have conducted many prospective case-control studies on the effects of different drugs in pregnancy. One study, published in 2002, found a significantly higher rate of neonatal withdrawal symptoms in newborns exposed to paroxetine in the third trimester, compared with unexposed controls.