Feb. 3, 2004 -- The FDA should put out a stronger warning about the risk of suicide in kids who take antidepressant drugs, an FDA advisory panel says.
That's one of three conclusions the panel reached after its 12-hour session on Monday.
The panel concluded that this is "a reasonable possibility that some people are made worse by these drugs and we should be telling people that," an FDA spokesperson tells WebMD. "They said the FDA should take an interim step to provide this information to parents and to physicians."
The panel made two other recommendations:
- Pharmaceutical company data from clinical trials of antidepressants in children and teens contains "signals" that some patients may become more suicidal after taking them. The panel endorsed an FDA plan to have an independent group at Columbia University comb through this data for more definitive information.
- The FDA must urge doctors who prescribe antidepressants to follow patients closely for signs of suicidal behavior or thinking.
Suicide and Antidepressants: No Clear Answers
Do antidepressants make some children suicidal? If so, do the drugs' benefits outweigh their risks?
Clinical trials usually provide answers to these questions. But when it comes to the question of whether antidepressants do children and teens more harm than good, there's no clear answer.
Last month, a task force for the American College of Neuropsychopharmacology issued its own interpretation of the published data on antidepressants and children. Not surprisingly, these psychiatrists and pharmacologists found that the benefits of the SSRI class of antidepressants -- which includes Celexa, Lexapro, Paxil, Prozac, and Zoloft -- outweighed their risks to young people.
But even this group admitted that it had not seen most of the data, and that its findings had to be considered "preliminary." That's because much of it remains in the hands of the pharmaceutical companies that sponsored the studies.
Thomas P. Laughren, MD, is the FDA's team leader for psychiatric drug products. His team has made heroic efforts to comb through the drug-company data and published studies to evaluate antidepressants' actual benefits and risks for children and teens.
In a January 5 memo sent to members of the advisory panel, Laughren finds little evidence that antidepressants are effective in children.
"We at the FDA, however, do not view negative studies as proof of no benefit," he writes. "Nevertheless, the failure of most of these programs to show a benefit in major depressive disorder does heighten the concern about the possibility of certain risks that may be associated with these drugs."
To find out more about these risks, Laughren's team asked the drug companies to comb through their data for any sign that antidepressants increased suicidal thoughts or behaviors. The results were disappointing. The different companies interpreted the FDA request in different ways, making the resulting information difficult to interpret.
Given the same data, however, British authorities were quick to act. The U.K. Medicines and Healthcare Products Regulatory Agency strongly advised doctors not to use the drugs in children and teens. Further, they insisted that the drugs' labels carry this warning. As of Dec. 10, 2003, the U.K. effectively bans Paxil, Effexor, Zoloft, Celexa, and Lexapro for children and teens. Only Prozac is seen to have a favorable risk-benefit profile.
Patient Advocates on Both Sides
Patient advocates are arguing both for and against antidepressants for children. The National Mental Health Association is strongly urging the FDA to approve the drugs. The Center for Science in the Public Interest is demanding that the FDA remove three panel members because of financial support from the pharmaceutical industry. And the Alliance for Human Research Protection says the FDA has "stacked the deck" by denying independent scientists sufficient opportunity to present crucial research findings.
The FDA's Laughren offers the panel a way out. He's asked a Columbia University group to act as an independent consultant to review the drug company data. This solution may get the FDA panel off the hook -- but it won't make everybody happy.
Clinical trials don't conclusively show that antidepressant drugs work. That's because the studies compare the drug to inactive placebo. And depressed patients who enroll in clinical trials, have interactions with medical staff, and receive realistic-looking sugar pills tend to get better. This so-called "placebo effect" can be a nightmare for drug trials.
University of Connecticut psychologist Irving Kirsch, PhD, says that 75% of the effect of SSRI antidepressants -- and 97% of the effect of the older, tricyclic antidepressants -- is due to the placebo effect.
Children react differently to antidepressants than adults. And there's reason to think that antidepressants may, in some people, lead to changes in brain chemistry that make suicidal behavior more likely.
Psychotherapy can help depression. But different clinicians do different kinds of psychotherapy, making this very difficult to measure in clinical trials. One kind of therapy -- cognitive-behavioral therapy -- is standardized. And clinical trials do show it to be effective -- but far from a cure-all.
The FDA advisory panel will meet again this summer. Then the heat will be on. They'll have to recommend which course the FDA should take.
SOURCES: Susan Cruzan, FDA. Laughren, T. Memorandum: Background comments for Feb. 2, 2004 Meeting of Psychopharmacological Drugs Advisory Committee and Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee, Jan. 5, 2004. News release, National Mental Health Association. News release, Center for Science in the Public Interest. News release, Alliance for Human Research Protection. FDA Testimony of Dr. Irving Kirsch and Dr. David Antonuccio on the Efficacy of Antidepressants With Children, Alliance for Human Research Protection, Feb. 2, 2004. FDA.