FDA Advisory Committee Recommends Black Box Warnings on Antidepressants
Following a two-day hearing on the safety and efficacy of antidepressants in children, an FDA advisory panel on Tuesday voted 15-8 to recommend that all antidepressants carry a black box warning -- the strongest warning issued by the government -- to inform consumers that the drugs can cause suicidal thoughts and behavior in patients under age 18, the Boston Globe reports (Dembner/Wirzbicki, Boston Globe, 9/15). A black box warning is a black section with white writing that appears at the top of drug inserts distributed to physicians and patients (Mulkern, Denver Post, 9/15).
On Monday, FDA officials said that an analysis of 15 clinical trials -- some of which were not made public for years -- has found that there is a "consistent link" between the use of any kind of antidepressant and suicidal tendencies in children. Tarek Hammad, an FDA analyst who conducted the latest review, said that between 2% and 3% of children treated with antidepressants had suicidal thoughts or behavior as a result of taking the drugs, adding that the increased risk is "beyond the suicidality as a result of the disease being treated."
The analysis has led FDA officials to revise their 10-year position that any increase in suicidal tendencies in children was the result of their underlying depression (California Healthline, 9/14).
If approved, the black box warning would go "much further" than FDA's decision in March to require antidepressant manufacturers to strengthen warning labels urging physicians to carefully monitor patients for worsening depression and suicidal thoughts, the Wall Street Journal reports (Wilde Mathews/Windham, Wall Street Journal, 9/15). That warning made no mention of a specific risk in children, and it did not state that the drugs could cause suicidal behavior (Shogren, Los Angeles Times, 9/15).
In addition to including a warning on the risk of suicide in children, the black box may state that studies conducted on several antidepressants have found the drugs are ineffective in children, according to Dr. Robert Temple, director of FDA's Center for Drug Evaluation and Research (Elias, USA Today, 9/15). Currently, Prozac is the only antidepressant that studies have shown to be effective in children and that has received FDA approval for children's use; other antidepressants are prescribed to children on an off-label basis (California Healthline, 9/14).
The advisory panel considered excluding from the warnings some of the nine antidepressants currently marketed and weighed whether the warning should also apply to older, less frequently prescribed antidepressants and to new drugs under development (Los Angeles Times, 9/15). The committee voted unanimously that it was "unable to conclude that any single antidepressant agent is free of risk at this time" based on clinical data analyzed by FDA (Wall Street Journal, 9/15).
"We have very strong evidence of harm and not very strong evidence of efficacy," panel member Thomas Newman, a professor of epidemiology at the University of California-San Francisco, said, adding, "It would not be bad if use of these drugs were diminished" (Vedantam, Washington Post, 9/15).
The panel also unanimously voted to recommend that FDA require drug makers to attach patient guides to antidepressants' packaging to describe the "risks of suicide in plain language," the New York Times reports (Harris, New York Times, 9/15). Committee members also suggested that the pamphlets detail potential warning signs of suicidal thoughts and behavior (Boston Globe, 9/15). While hundreds of drugs must carry black box warnings, fewer than 30 require patient information attachments, according to FDA officials (New York Times, 9/15).
The panel recommended FDA also require parents to sign a form stating they understand the risks of the drug (Anderson, Atlanta Journal-Constitution, 9/15).
Temple said FDA has already been considering drug label changes for antidepressants and will make a decision on the advisory panel's recommendations within a few months (New York Times, 9/15). If FDA decides to include a black box warning on antidepressants, it will write the warning in consultation with drug makers (Boston Globe, 9/15).
Temple added that FDA is "reconsidering" its general policy of not including data from failed efficacy trials on drug labels. In addition, the agency plans to require pediatric trials of antidepressants to include a head-to-head comparison to a drug that has already been proven effective, rather than just a placebo (Wall Street Journal, 9/15).
Several advisory panel members said that a black box warning could discourage drug companies from direct-to-consumer advertising of antidepressants because, while the warning does not prohibit such marketing, it requires that advertisements include the warnings, which "could make them unappealing or unfeasible," the Washington Post reports. The black box would also "raise the stakes for physicians deciding whether to prescribe drugs," according to the Post (Washington Post, 9/15).
Last year, physicians wrote about 15 million prescriptions for nine antidepressants for patients under age 18, according to data from IMS Health and FDA (Los Angeles Times, 9/15). After the new warnings were issued in March, antidepressant prescriptions for children still increased by nearly 8% (New York Times, 9/15). The warning could "make (doctors) think twice about prescribing the drugs," Dr. P. Joan Chesney, chair of the advisory committee, said (Los Angeles Times, 9/15).
Some members of the panel expressed concern that the warning could cause physicians to leave children's depression untreated. Dr. Matthew Rudorfer, a panel member from the National Institute of Mental Health, said 15% of children with untreated depression commit suicide -- a greater risk than that presented by the drugs themselves (New York Times, 9/15).
Several broadcast programs reported on the FDA advisory committee's ruling:
- CBS' "Evening News": The segment includes comments from Dr. Harold Koplewicz, a psychiatrist at New York University's Child Study Center, and a parent who attended the hearing (Kaledin, "Evening News," CBS, 9/14). The complete segment is available online in RealPlayer.
- NPR's "All Things Considered": NPR's Joanne Silberner discusses the hearing (Silberner, "All Things Considered," NPR, 9/14). The complete segment is available online in RealPlayer.
- NPR's "Morning Edition": The segment includes comments from Dr. Wayne Goodman, chair of the FDA advisory committee; James McGough, associate professor of clinical psychiatry at the University of California-Los Angeles; Barbara Wells, dean of the School of Pharmacy at the University of Mississippi; and parents and children who testified at the hearing (Silberner, "Morning Edition," NPR, 9/15). The complete segment is available online in RealPlayer.