BioEd Online

A re-evaluation of clinical data suggests that although antidepressants do promote suicidal tendencies in a small percentage of children and adolescents — as widely reported a few years ago — the benefits of the drugs for the treatment of depression and anxiety disorders almost always outweigh the risks.

The new study, published this week in the Journal of the American Medical Association, makes use of data that were not available when the US Food and Drug Administration (FDA) evaluated the drugs for their safety in children in 2004. The findings from that evaluation led to the placement of a so-called 'black box' warning label on antidepressants, cautioning consumers that the drugs could cause suicidal tendencies in individuals under the age of 18. Black-box warnings are the strongest alerts the agency can assign before banning a drug.

After the FDA review, Jeffrey Bridge, an epidemiologist at Ohio State University in Columbus, and his colleagues worried that the negative publicity surrounding the drugs had shifted attention away from any benefit the treatments might offer to children suffering from depression and other anxiety disorders. "The black-box warning showed us that there was a risk of suicidal thinking and behaviour, but it didn't take benefit into account," says Bridge. "We wanted to balance the discussion."

Their new analysis concludes that study participants were much more likely to experience some relief from their symptoms than to turn towards thoughts of suicide. That's in line with other studies looking at the benefits of these drugs, says Bridge. But it is useful to have an up-to-date confirmation after the 2004 FDA report, he notes.

None of this means that the warning label should be changed, says Bridge — at least not until more data on long-term use is collected. But his study emphasizes that the warning message should be taken in the right spirit — as a call to monitor young people taking the drugs, rather than to stop people from using them. Some experts say the evidence shows that this isn't happening.

There are no plans to alter the warning message on these drugs, says Thomas Laughren, director of the Division of Psychiatry Products at the FDA's Center for Drug Evaluation and Research, in a written statement: "At this time, nothing indicates a need for change in the 'black box' warning, which urges attention to patients starting treatment (still good advice), and does not suggest avoiding the drugs."

Risk-benefit analysis

Bridge and his colleagues analysed 27 clinical trials in which a particular class of antidepressant — known as selective serotonin reuptake inhibitors — was used to treat children and adolescents with major depressive disorder, obsessive-compulsive disorder, or other anxiety disorders.

Their data set included several clinical trials that were performed after the FDA's evaluation, increasing the overall number of patients studied by around 20%.

There were no attempted suicides among the group of more than 5,300 subjects studied, although the analysis did reveal that children and adolescents taking the drugs had a 1% increase in their risk of thinking suicidal thoughts or attempting suicide¹. But the benefits were more dramatic. For example, children and adolescents with obsessive-compulsive disorder were 20% more likely to respond positively to the drug than the placebo.

Off label

Gregory Simon, a psychiatrist at the Group Health cooperative healthcare system in Seattle, Washington, points out that the black-box warnings have not worked to convey the idea that the drugs should still be used when appropriate, but that young people should be monitored more closely. "From a public-health perspective I don't think the labels have accomplished what the FDA wanted them to," says Simon.

There is no evidence that any additional patient monitoring is taking place, Simon says, and antidepressant prescriptions declined soon after the warning labels were added.

Only about 20% of patients who are prescribed antidepressants return to their doctor for the recommended minimum of three follow-up visits in the 12 weeks following their diagnosis, according to the National Committee for Quality Assurance, a nonprofit organization that evaluates health care and is based in Washington, DC. Black-box labels have had no effect on those numbers, which have remained largely unchanged since 1999.

"The problem is that the healthcare system is generally well organized to respond to the patients who show up in the office, but not the ones who don't come back," says Simon.