Families and doctors should be cautioned that children taking antidepressant drugs may be at an increased risk for suicidal behavior and thinking, and the government should require a prominent "black box" warning label on the medications, an expert panel concluded yesterday.
If adopted, the recommendation by the panel advising the Food and Drug Administration would mark a significant shift in the government's regulatory stance toward the widely used drugs -- which include Prozac, Paxil, Zoloft and Celexa -- for treating children with depression, anxiety, obsessive-compulsive disorder or other conditions.
Such a warning would raise the stakes for physicians deciding whether to prescribe the drugs and would encourage parents and doctors to pay much closer attention to research that has raised questions about whether the drugs are safe and effective for children, experts said.
Expressing the dilemma faced by the expert panel, chairman Wayne Goodman, a psychiatrist at the University of Florida in Gainesville, said he wanted to discourage casual use of the drugs while preserving doctors' ability to carefully assess children and prescribe the medications when needed.
"We can't ignore there is data out there that points to the effectiveness and protective action of these drugs against suicide," Goodman said. "Given what we know, I am not ready to ban the antidepressants."
Several psychiatrists told the panel during two days of hearings that the failure of many studies to show that the drugs worked does not mean they are ineffective. Many families testified that the medications helped their children.
But panel member Thomas Newman, a professor of epidemiology at the University of California at San Francisco, said, "We have very strong evidence of harm and not very strong evidence of efficacy. It would not be bad if use of these drugs were diminished."
The panel's recommendation comes as use of the medications has soared despite growing evidence of their risks. Many panel members blamed pharmaceutical industry marketing for prompting clinicians to prescribe the drugs.
Short of an outright ban, a "black box" warning is the most serious caution the FDA can require. Several panel members said they hope it would discourage drug companies from advertising antidepressants to patients, especially through television. The warning would not preclude such marketing, experts said, but the requirement that the caution be included in any ads could make them unappealing or unfeasible.
The rulings came at the end of two days of high drama in Bethesda, where experts were told about a new FDA analysis of 24 antidepressant trials that showed that children taking a range of drugs had twice the rate of suicidal behavior and thinking compared with those who took dummy pills, or placebos.
The panel had to wrestle with a problem unique to psychiatry: Depression is itself associated with suicide, and many specialists believe the drugs reduce the risk.
While there is no conclusive evidence of this, studies have shown that suicide rates dropped among populations of children as the prescribing of antidepressants increased. Some experts believe the medications, many of which belong to a class of drugs called selective serotonin reuptake inhibitors, or SSRIs, may increase the risk of suicide among some children while reducing it in others.
"If there were no SSRIs, would there be more suicides, fewer suicides or the same number of suicides in children?" panel member Norman Fost, professor of pediatrics and bioethics at the University of Wisconsin Medical School, asked at the start of yesterday's session.
Robert J. Temple, the FDA's associate director for medical policy, said there are no data to answer that question.
But most of the panelists agreed that the enthusiasm for the drugs among American physicians was not supported by the research. Many noted with concern that with the exception of Prozac, none of the antidepressants have been approved by the FDA for treating depression in children. Most children are prescribed the medications "off label" -- based on physicians' belief that the drugs are safe and effective. Once a drug has been cleared for the market, physicians are free to use it even for conditions not specifically endorsed by the agency.
The panel's recommendation, on a 15 to 8 vote, left the FDA in the potentially awkward position of having to warn physicians about using the drugs for purposes that the agency has not approved.
While the agency traditionally avoids telling doctors how to practice medicine, many panel members argued that drug marketing was superseding science: Although companies cannot promote most of the antidepressants for childhood depression -- an unapproved use -- they can aggressively market the same medications for adults.
The experts noted that although Prozac is the only drug specifically approved to treat depression in children, the top-selling antidepressant for youngsters is Zoloft. Two trials of Zoloft failed to show the medication was superior to sugar pills in depressed children.
Prozac is no longer being actively marketed because its patent has expired; Zoloft is still being promoted.
Temple said the FDA would weigh whether to include specific information on each drug's label detailing how the drug had performed in clinical trials.