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 a new study has found that the drop coincides with an unprecedented increase in the number of suicides among children.
From 2003 to 2004, the suicide rate among Americans younger than 19 rose 14 percent, the most dramatic one-year change since the government started collecting suicide statistics in 1979, the study found. The rise followed a sharp decrease in the prescribing of antidepressants such as Prozac, Zoloft and Paxil after parents and physicians were confronted by a barrage of warnings from the Food and Drug Administration and international agencies.
The data suggest that for every 20 percent 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.
'Black box warning'
Thomas Insel, director of the National Institute of Mental Health, said, "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."
The new finding, published in the September issue of the American Journal of Psychiatry, is the latest development in a controversy marked by complex science and passionate advocates. In 2003 and 2004, the 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 percent decrease in antidepressant use among children between 2003 and 2005. The suicide rate among youngsters there increased by 49 percent in that period.
Few other plausible explanations
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 said. "They may not be getting SSRIs, but they are getting psychotropics."
The new 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.
The 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.
Thomas Laughren, director of the agency's division of psychiatry products, said, "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 percent."
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."