Antidepressants May Permanently or Reversibly Affect Fetal Brain Development

Laurie Barclay, MD
Medscape.com

March 2, 2010 — Antidepressants may permanently or reversibly affect fetal brain development depending on the timing of exposure during pregnancy, according to the results of a study reported online February 22 in the March issue of Pediatrics.

"In animals, antidepressant exposure in early life causes changes that persist into adulthood," write Lars Henning Pedersen, MD, PhD, from Aarhus University in Aarhus, Denmark, and colleagues. "Results from human studies have been equivocal and either found no association between antidepressants and fetal brain development or suggested subtle effects on fine motor development."

The goal of the study was to evaluate whether there is an association between antidepressant exposure in utero and achievement of developmental milestones at ages 6 and 19 months, using data from the Danish National Birth Cohort. Of the pregnant women in this cohort who were eligible for the study, 415 reported use of antidepressant medication, 489 reported depression without medical treatment, and 81,042 reported neither depression nor use of psychotropic medication.

Compared with children of women not exposed to antidepressants, children with second- or third-trimester exposure to antidepressants were able to sit up 15.9 days later (95% confidence interval [CI], 6.8 - 25.0) and to walk 28.9 days later (95% CI, 15.0 - 42.7). However, these milestones were still within the normal range of development.

Compared with children of women not exposed to antidepressants, fewer children with second- or third-trimester exposure to antidepressants could sit without support at age 6 months (odds ratio [OR], 2.1; 95% CI, 1.23 - 3.60), and fewer could occupy themselves at age 19 months (OR, 2.1; 95% CI, 1.09 - 4.02). There were no statistically significant associations of any of the other milestones measured with in utero antidepressant exposure.

Limitations of this study include possible confounding by the severity of disease, lack of blinding of the participants or the interviewers, and not all women completing the 4 interviews.

"The results of this study suggest a permanent or reversible effect of antidepressant exposure on fetal brain development, which may depend on the timing of exposure during pregnancy," the study authors write. "We found associations between exposure to antidepressants in late pregnancy and motor development, particularly for boys. The clinical and public health relevance of the results is not known, and longer follow-up monitoring of the children is needed."

The Lundbeck Foundation funded this study, which also received support from the National Danish Research Foundation, Aarhus University, the Danish Society of Obstetrics and Gynecology, the Ville Heise Foundation, and the Rosalie Petersen Foundation. Drs. Pedersen and Olsen received grants from the Lundbeck Foundation, which is an independent foundation supported by the pharmaceutical company Lundbeck.

Pediatrics. Published online February 22, 2010.

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Authors and Disclosures
Journalist
Laurie Barclay, MD

Freelance writer and reviewer, Medscape, LLC

Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

$2.5M verdict over birth defects blamed on Paxil

Associated Press
By MARYCLAIRE DALE (AP)
October 14, 2009

PHILADELPHIA — A jury ordered GlaxoSmithKline to pay $2.5 million to a woman whose son was born with serious heart defects after she took the antidepressant Paxil during her pregnancy.

The closely watched verdict handed down Tuesday in Philadelphia was the first of about 600 similar cases pending across the country that blame Paxil for heart problems and other birth defects.

The jury found GlaxoSmithKline guilty of negligence but not outrageous conduct, and rejected punitive damages. The company vowed to appeal.

"The adverse events started to come in the late 1990s, early 2000. The evidence was overwhelming and alarming," said lawyer Jamie Sheller, who represented plaintiff Michelle David. "They could have known this way, way before they did, way before they changed the label in 2005."

Paxil was classified as a drug with no known link to increased birth defects from its introduction in 1992 through 2005. The Food and Drug Administration began warning in September 2005 that Paxil may be associated with birth defects and strengthened the warning four months later.

David, 28, of Bensalem delivered her full-term son, Lyam Kilker, in October 2005.

He was diagnosed with heart defects two months later and spent five months in a Philadelphia hospital, undergoing surgery to repair two holes in his heart, lawyer Jamie Sheller said Wednesday. He also has a third, separate heart defect and will need at least one more surgery as he grows, she said.

David, a dance teacher and former Philadelphia 76er cheerleader, has no history of heart defects in her family, her lawyer said.

GlaxoSmithKline argues that birth defects occur in 3 to 5 percent of all live births, whether or not the mother took medication during pregnancy.

"The scientific evidence does not establish that exposure to Paxil during pregnancy caused his condition," the drugmaker said in a statement. "Once approved for use, the company acted properly in marketing the medicine, including monitoring its safety, updating pregnancy information in the medicine's labeling as new information became available, and in communicating important safety information to regulatory agencies, the scientific community and the public.

Plaintiffs lawyers will continue to pursue punitive damages in the hundreds of remaining cases, the next of which is set for trial in Philadelphia in November.

"We're starting to chip away at this story, but even as we speak, we're still fighting them, documents are still being produced, depositions are still being taken," Sheller said.

Sales of Paxil totaled $849 million last year.

Paxil has competed fiercely in the marketplace at times with rival antidepressant blockbusters like Eli Lilly's Prozac and Pfizer's Zoloft. The drug no longer has patent protection and now competes against cheaper generic versions.

Copyright © 2009 The Associated Press. All rights reserved.