New research is raising more concerns about the safety of the most widely prescribed antidepressants (search) in pregnant women and young children. A new study of mice suggests that early exposure to drugs like Prozac could increase the chances of developing depression and anxiety disorders later in life.

Columbia University researchers found that mice exposed to Prozac shortly after birth exhibited abnormal emotional behavior in adulthood that appeared to result from a drug-related disruption of a key growth factor linked to brain development.

The findings were made public Tuesday at the annual meeting of the Society for Neuroscience in San Diego. They will also be published in the Oct. 29 issue of the journal Science.

Earlier this month, the FDA ordered drug manufacturers to include warnings on the packaging of Prozac and similar drugs about a possible increased risk of suicidal thoughts or behaviors among children and adolescents who take them. These depression drugs, called selective serotonin reuptake inhibitors (search) (SSRIs), include Prozac, Celexa (search), and Zoloft, (search) and several others.

The latest study offers more evidence that the drugs may not be as safe as once thought, although its researchers point out that the relevance of the findings in humans is not known.

"We are hoping that this work will serve as impetus for doing the kind of clinical studies necessary to find out if there are long-term risks associated with these drugs," Columbia University psychiatry professor Jay A. Gingrich, MD, PhD, tells WebMD.

Stressed-Out Rodents

SSRIs work by inhibiting the absorption of the brain chemical serotonin by the serotonin transporter 5-HTT.

Earlier studies in animals have identified serotonin as a key growth factor for brain development.

In the newly published study, the Columbia University researchers examined the effects of SSRI exposure in mice at a period in life that corresponded roughly to the last trimester of pregnancy through age 8 in humans.

As expected, mice lacking the 5-HTT gene exhibited abnormally high anxiety levels as adults, with or without early exposure to Prozac.

Mice with the intact gene who had no early-life exposure to Prozac exhibited normal anxiety levels as adults.

However, mice with the intact 5-HTT gene who were exposed to Prozac as newborns behaved more like the 5-HTT gene-deficient mice. They showed abnormally high anxiety levels.

More Study Needed

The researchers conclude that by blocking the absorption of serotonin, Prozac may stimulate the abnormal activation of several other receptors in the developing brain, leading to abnormal development.

"These are mice, so we don't know what the impact is on the developing human brain," Gingrich says. "But if there has been a trend toward complacency in prescribing these drugs and a thinking that they carry no risks for pregnant women and young children, this is something new to consider."

Emory University psychiatry professor Paul Plotsky, PhD, is also studying the effects of early SSRI exposure on brain development. Preliminary data from his own research in mice suggests that repeatedly going on and off SSRIs while the brain is still developing may lead to bipolar disorder.

In another study, the researcher found that 6-month-old babies born to mothers taking SSRIs exhibited higher than normal anxiety levels during physical exams.

"These drugs have been thought to be safe because there is no overt evidence that they are not, but they could be driving subtle changes in the brain and basically building in risk factors for psychological problems," he tells WebMD. "But depression is also very dangerous, so it is important that we understand the risks and benefits of these drugs."

Tallie Baram, MD, PhD, calls the new findings compelling but says there needs to be further study. Baram is a professor of psychiatry at the University of California, Irvine.

"The fact that they found this in mice is an eye opener," she says. "But there is still a lot of work to be done to understand its relevance."

By Salynn Boyles, reviewed by Brunilda Nazario, MD

SOURCES: Ansorge et al. Science, Oct. 29, 2004; pp 879-881. Neuroscience 2004, San Diego, Oct. 23-27, 2004. Jay A. Gingrich, MD, PhD, department of psychiatry, Columbia University College of Physicians and Surgeons, New York. Paul Plotsky, PhD, professor, department of psychiatry, Emory University, Atlanta. Tallie Baram, MD, PhD, professor of psychiatry, University of California, Irvine.