A scientific advisory panel urged the Food and Drug Administration on Monday to issue stronger warnings to doctors about the possible risks to children of a newer generation of antidepressant drugs, rather than wait until the agency’s review of the drugs is completed.
“Our sense is that we would like in the interim for the FDA to go ahead and issue stronger warning indications to clinicians” about the chance that the antidepressants might be linked to suicidal thinking and behavior, hostility or other forms of violent behavior, said Dr. Matthew Rudorfer, a scientist at the National Institute of Mental Health and the chairman of the FDA advisory committee.
Rudorfer said that such a warning should not discourage doctors from using the antidepressants but would alert them to warning signs that a drug might be having harmful effects. The recommendation came at the end of an emotional daylong public hearing on the issue. Most of the antidepressants belong to the class known as selective serotonin reuptake inhibitors, or SSRIs.
Dr. Thomas Laughren, the team leader for the FDA’s division of neuropharmacological drug products, said the agency took the committee’s recommendation “very seriously” and that it would probably issue such a warning “sooner rather later.”
The FDA has been conducting its own review of the safety and effectiveness of the antidepressants, but has not taken action to stiffen warning labels or restrict use of the drugs.
Along with experts who testified at the hearing, the panel listened to parent after parent, and children, who stepped up to the microphone to tell stories of suffering and loss.
A father spoke of his 13-year-old son who hanged himself from a closet hook after starting on an antidepressant. A teenager said that after a few weeks on the drugs, he took a hunting rifle to school and threatened his classmates. He had no memory of his actions, he said, and woke up afterward in a juvenile detention center.
“How many more people have to die before a warning gets issued?” asked one mother.
Other parents said the antidepressants had helped their children enormously and saved many other children’s lives.
“I shudder to think of their plight if these medications were not available,” said a mother whose son suffers from manic-depression.
Rudorfer said the committee was struck by the fact that in some cases described at the hearing, doctors had seemingly prescribed antidepressants casually and failed to monitor the children closely while they were taking them.
“We were all concerned about the stories we heard,” Rudorfer said, noting that the drugs are “very powerful but also potentially very effective.”
In December, British drug regulators told doctors to stop writing new prescriptions for six newer antidepressants because the potential risks outweighed their benefits. Use of the drugs might still be warranted in some cases, the regulators said, and they exempted Prozac from the order.
Laughren told the advisory committee on Monday that the agency is reviewing 25 studies of nine antidepressants, involving more than 4,000 patients. The drugs under review include Prozac, which is made by Eli Lilly; Zoloft, by Pfizer; Paxil, by GlaxoSmithKline; Luvox, by Solvay; Celexa, by Forest Laboratories; Wellbutrin, by GlaxoSmithKline; Effexor, by Wyeth; Serzone, by Bristol-Myers Squibb; and Remeron, by Akzo Nobel.
He said there is “a suggestion from that data that there is a signal of something, there is an excess of something occurring.” But trying to figure out what that “something” is, Laughren said, is enormously complicated.
At the hearing on Monday, Laughren and other FDA officials asked the scientists on the committee to advise them on several questions, including whether their plans for analyzing the existing studies of the antidepressants are adequate.
The FDA has asked researchers at Columbia to track back the data used in the clinical trials of the drugs to make sure that behaviors coded in the trials as suicidal in fact represent suicidal thoughts or actions.
Parents and some psychiatrists have been critical of the FDA for taking so long to conduct its investigation.
About 11 million prescriptions for a group of newer antidepressants were written for children under 18 in 2002 in the United States, according to the FDA.
Some of the parents at the hearing, who had two minutes each to tell their stories, described how their children seemed to change abruptly after starting the drugs, becoming aggressive, suicidal or violent towards others.
But Dr. David Shaffer, a professor of psychiatry at Columbia, told the advisory panel that suicide rates among children and adolescents has declined in recent years, and that the growing use of antidepressants was one possible explanation.
