The new "black box" warning—the FDA's strongest possible label—will alert people younger than 25 to a similar risk. And in an unusual move, it will state that depression and some other psychiatric disorders "are themselves associated with increases in the risk of suicide."
If the warning seems to suffer from a split personality, it mirrors an ongoing debate among researchers and patient advocates about the risks and benefits of antidepressants.
The FDA's Psychopharmacologic Drugs Advisory Committee recommended in December that the warning be expanded to cover young adults. The panel had reviewed 295 trials of antidepressants that included 77,000 adults of all ages who suffered from major depressive disorder (MDD) and other psychiatric conditions.
Reviewers concluded that, compared with a placebo, antidepressant treatment had led to five additional cases—twice the rate—of suicidal thoughts or behavior (suicidality) per thousand adults aged 18 to 24.
The risks from drugs and placebos were roughly equal in those aged 25 to 64, and antidepressants led to six fewer cases than a placebo in those 65 and older, according to the proposed FDA warning, which includes a table breaking down the risks by age group. The number of successful suicides, however, did not show a clear trend.
For young adults, "the risk is quite small, but we think it is a real risk and it's something that needs to be paid attention to," said Thomas Laughren, director of the FDA's Division of Psychiatry Products, at a press conference yesterday.
The same FDA panel recommended in 2004 that the black box warnings be added to 34 drugs, from Anafranil to Zyban. The warning advised patients to consider both the risks and benefits of treatment, but some experts were concerned it would scare off patients who might benefit from the drugs.
Prescription rates for antidepressants fell in 2004, after the FDA first made public announcements about their risks. Perhaps coincidentally, the teen suicide rate rose 18 percent between 2003 and 2004, the latest years for which data is available.
"The coincidence of a decrease in prescribing and an increase in adolescent suicides after years of suicides coming down is a concern," Laughren said. "We don't know specifically whether or not the black box has been the cause of either," he said.
The suicide trend is "worrisome," agrees David Brent, a child psychiatrist at the University of Pittsburgh Medical Center. Last month Brent and colleagues published a pooled analysis of 27 trials for MDD and other psychiatric problems in kids, in which they compared the total number of individuals successfully treated with those harmed during the first couple months of treatment with one of several antidepressants.
"Many more people benefit from the drug than experience suicidal thoughts," Brent says, "So the question is what is this expanded label going to do?"
The risks of antidepressants may be small, but so are the measured benefits, says clinical psychologist David Antonuccio of the University of Nevada School of Medicine. In the Brent group's analysis, he notes, 50 percent of those suffering from MDD responded to a placebo, compared with 61 percent who responded to treatment—specifically, to Prozac, the only drug approved by the FDA for treatment of depression in children or teens.
"This comes down to informed consent," Antonuccio says. Depression requires treatment, but other treatments are less risky, if less effective, he adds.
"The value of the warning label is that it alerts parents, physicians and patients to the possibility that some kids can become more agitated" on antidepressants, Antonuccio says. "That's a very important piece of information."