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David Baxter PhD

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Antidepressants Lower Kids' Suicide Risk, New Research Finds
By Amanda Gardner, HealthDay
Wed Nov 1, 2006

The debate about how antidepressants might affect suicide risk in children and adolescents just got murkier.

Spurred by reports of suicidality in pediatric antidepressant users, the U.S. Food and Drug Administration two years ago slapped a "black box" warning on popular selective serotonin reuptake inhibitor (SSRI) drugs such as Celexa, Paxil, Prozac and Zoloft, warning of the possible risk.

But now a new study has found that this class of drugs may actually reduce the risk of suicide in troubled children and adolescents.

The finding has some experts worried that the "black box" warning will actually cause youth suicide rates to rise.

"Rather than take the 'black box' warning and say children should be followed very carefully, many of us are concerned that physicians are going to say, 'It's not worth it,'" said study author Robert Gibbons, a professor of biostatistics and psychiatry at the University of Illinois at Chicago. "If depressed kids are not receiving treatment, we may find that completed suicide rates may increase," he added. "That's the big concern."

The study, which is published in the November issue of the American Journal of Psychiatry, "certainly doesn't make it clear that's what's happening, but what we do know is that there is an inverse association," Gibbons said.

According to the study, in 2002 suicide was the fifth leading cause of death in children and adolescents aged 5 to 14. In the 10-to-14 age group, suicide was the third leading cause of death behind accidents and cancer.

Pediatric use of antidepressant medications, and especially SSRIs, has been the subject of extended controversy, however. In October 2004, the FDA directed manufacturers of SSRIs to put a special "black box" warning on the drugs' labeling. The warning would alert health -care providers to an increased risk of suicidality in children and teens using the medications. In July 2005, the FDA issued a public health advisory raising the possibility that the risk of suicidality also applied to adults taking SSRIs, after several studies pointed that way.

The authors of the current study looked at county-by-county suicide data across the United States for children aged 5 to 14 for the period 1996 through 1998. This information was cross-referenced with county-by-county prescription information.

Counties with the highest prescription rates for SSRIs had the lowest suicide rates in these age groups, the researchers found.

In counties with low antidepressant prescription rates, the suicide rate was as high as 1.7 per 100,000. That rate plummeted to as low as 0.7 per 100,000 in counties with high prescription rates.

Suicide rates were also highest in less densely populated parts of the western United States, areas that often include Indian reservations. Suicide rates were lowest in large metropolitan areas such as Chicago, New York, Boston, Los Angeles, San Diego, Seattle and Miami.

Based on the findings, the researchers estimated that if no prescriptions for SSRIs were written, there would be 253 more suicides each year among U.S. children and adolescents.

The finding "is not a surprise," said Dr. Grant Mitchell, chief of psychiatry at Northern Westchester Hospital in Mt. Kisco, N.Y. "There is a much greater risk of suicide in patients who are depressed and are untreated than there is from the use of SSRIs in terms of side effects."

It's not yet clear if there's been a cause-and-effect relationship between the drop in SSRIs use among children and any rise in suicide, according to Gibbons.

"What we don't know is if that has led to an increase or decrease in the suicide rate," he said. "It's going to be hard to ascertain because the U.S. Centers for Disease Control and Prevention (CDC) have not made those data available. We're working closely with the CDC to get those data."

Gibbons was a member of the 2004 FDA advisory panel that voted 15-8 in favor of placing the "black box warning" on SSRI prescriptions. Gibbons himself voted against the black box warning.

"There's certainly an implication that the 'black box' warning may lead to an increase in suicide, but we don't know that yet," Gibbons said. "I think that whoever is thinking about these issues and the effect of the 'black box' warning should be thinking about getting the best possible data. This is an inherent problem."

Gibbons was also a member of the Institute of Medicine Committee on U.S. Drug Safety, whose recent report The Future of Drug Safety: Promoting and Protecting the Health of the Public was critical of the FDA.

"This is an important problem that we face in terms of understanding the safety of a drug throughout its life cycle after the drug is approved by the FDA," Gibbons said.

His team's findings are consistent with the results of a study conducted by Dr. Julio Licinio, now the chairman of psychiatry and behavioral sciences at the University of Miami Miller School of Medicine.

"We looked at historical data in all age groups and found the same thing," said Licinio, who headed the study while at the University of California, Los Angeles. "The more that fluoxetine [Prozac] was prescribed, the less suicide you have."

But he also pointed out that the FDA's 'black-box' warning was based largely on data involving suicidality -- suicidal thoughts and ideas -- not suicide per se.

"Suicidality as an end point is questionable because it's how you feel -- and how you feel can change from moment to moment," he said. "Suicide is a much more important end point."

Both his study, the current study and yet another study out of Sweden all found that actual rates of suicide declined the more SSRIs were prescribed, Licinio said.
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