Youth suicides increased as antidepressant use fell.

Warnings from federal regulators four years ago that antidepressants were increasing the risk of suicidal behavior among young people led to a precipitous drop in the use of the drugs. Now new studies have found that the drop coincides with an unprecedented increase in the number of suicides among children.

A study published in the September issue of the "American Journal of Psychiatry" (AJP) found that from 2003 to 2004, the suicide rate among Americans younger than 19 rose 14%, the most dramatic one-year change since the government started collecting suicide statistics in 1979, "The Washington Post" reported Sept. 6.

The following day, the Centers for Disease Control (CDC) reported that the rate of suicide in Americans ages 10 to 24 increased 8% from 2003 to 2004, the largest jump in more than 15 years.

Some psychiatrists argue that the reason for the increase is the decline in prescriptions of antidepressant drugs like Prozac to young people since 2003, leaving more cases of serious depression untreated. Others say that it is impossible to know if the increase is linked to patterns of antidepressant prescriptions. The one-year spike in suicides could be a statistical fluctuation, they say, and not the start of a trend.

The increase was particularly sharp among adolescents, especially girls, CDC stated.

The data from the study in the AJP suggest that for every 20% decline in antidepressant use among patients of all ages in the United States, an additional 3,040 suicides per year would occur, said Robert Gibbons, a professor of biostatistics and psychiatry at the University of Illinois at Chicago, who did the study. About 32,000 Americans commit suicide each year.

CDC's analysis found that in 2004 there were 4,599 suicides in Americans ages 10 to 24, up from 4,232 in 2003, for a rate of 7.32 per 100,000 people that age. In the years before that, the rate had dropped to 6.78 per 100,000 in 2003 from 9.48 per 100,000 in 1990.

Thomas Insel, M.D., director of the National Institute of Mental Health, told The Post, "We may have inadvertently created a problem by putting a black box warning on medications that were useful." He added, "If the drugs were doing more harm than good, then the reduction in prescription rates should mean the risk of suicide should go way down, and it hasn't gone down at all--it has gone up."

However, Thomas Laughren, M.D., director of the division of psychiatry products at FDA., said in a conference call with reporters that the agency would need to see more data over time, linking declines in prescriptions to suicide risk before revisiting any of its decisions.

"You simply cannot reach causal conclusions" from the new CDC data, Laughren said.

These new findings are the latest developments in a controversy marked by complex science and passionate advocates. In 2003 and 2004, FDA issued a series of warnings that clinical trials had detected an increase in suicidal thinking among children and adolescents taking a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs), compared with children and adolescents given sugar pills. In late 2004, the agency called for a "black box" warning on the drugs to call attention to the potential risk, and expanded it last December to include young adults.

The warnings led to a broad decline in SSRI prescriptions for all patients younger than 60, Gibbons said. Prescription rates continued to rise among those older than 60, and this was the only group in which suicides dropped between 2003 and 2004, his study found.

The study included the Netherlands, which had a 22% decrease in antidepressant use among children between 2003 and 2005. The suicide rate among youngsters there increased by 49% in that period.

The trend lines do not prove that suicides rose because of the drop in prescriptions, but Gibbons, Insel and other experts said the international evidence leaves few other plausible explanations. Previous studies have shown that U.S. suicide rates are lower in counties where antidepressant use is higher, and a recent study of 200,000 depressed veterans found that those taking an antidepressant had one-third the risk of suicide of those who were not.

David Healy, a British psychiatrist who has been critical of the drugs, disagrees. He said that the increase in suicides was more likely caused by the growing use of antipsychotic drugs among children rather than a decline in antidepressant use. "I would be absolutely certain that the increase is not because kids are not being treated," he told The Post. "They may not be getting SSRIs, but they are getting psychotropics."

The AJP study was largely funded by the federal government. Pfizer, which makes Zoloft, provided some money for data collection, Gibbons said, but was not involved in the study and did not review the results before they were published.

FDA required the warnings on the drugs' labels to prompt doctors to closely monitor patients they put on antidepressants, because of some evidence that the risk of suicide is highest shortly after treatment begins. Gibbons said that the decision was misguided and that the situation called for better education of physicians, not warnings.

Laughren told The Post, "FDA is obviously concerned about possible negative impacts of labeling changes but also feels a strong obligation to alert prescribers and patients to possible risks associated with the use of antidepressants." He added, "We will continue to monitor antidepressant use and suicide rates, and will take appropriate regulatory actions as new data become available."

NIMH's Insel said it is possible that antidepressants are lowering the risk of suicide overall, even as they increase the risk among a subset of patients. New research to be published soon examines genetic factors that may put some patients at particular risk, he added.

If regulators base their decisions on risks alone, he said, "you focus on that very tiny number of kids who may be at greater risk when they are treated and you ignore the very large benefit that might accrue to the other 99.9%."

Insel acknowledged that it may be a while before physicians have tests that can reliably predict which patients are likely to become suicidal as a result of the drugs. In the interim, he said, "if I had a child with depression, I would go after the best treatment but also provide the closest monitoring."