FDA orders stronger warning labels on antidepressants
By Lauran Neergaard
The Associated Press
Tuesday, September 14, 2004
WASHINGTON - Antidepressants should come with the nation's strongest warning - in a black box on the label - that they can sometimes spur suicidal behavior in children and teenagers, the government's scientific advisers decided today.
It's a rare risk, and therefore families need detailed information on how to balance that concern with the need to treat depression, which itself can lead to suicide, cautioned advisers to the Food and Drug Administration.
So antidepressants prescribed to minors also should come with an easy-to-read pamphlet that explains how to decide if the child is an appropriate candidate for the drug and what are the warning signs of suicide, the panel concluded. Also, FDA should consider the extra step of making parents sign a form that they understand the risks before the child receives the first pill.
There may be a backlash to such strong warnings, cautioned FDA advisory committee chairman Dr. Wayne Goodman, psychiatry chairman at the University of Florida.
"It will make prescribing more difficult. I anticipate there will be alarm from parents and the child," said Goodman, who still backed the big step. "I think that's worth that complication, because it will raise the threshold to prescribing" these drugs to minors.
On the other hand, the drugs seem to help some desperately ill children, said panelist Jean Bronstein, a California nurse who opposed the black-box warning.
"The biggest message I heard from the consumer is they want to be warned about what the risk is," she said, referring to hours of emotional testimony Monday from families who blamed their children's suicides on drugs they didn't know might be risky.
Tearful families greeted Tuesday's decision with applause.
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On the second day of a panel meeting, FDA officials seemed to be leaning toward requiring the new labels, based on pediatric studies of nine antidepressants, including Eli Lilly's Prozac and Pfizer's Zoloft.
For many children, however, the benefits of taking the drugs may outweigh the risks, the agency said, asking an advisory panel of experts for input on whether labels for the drugs ought to be changed to reflect the risks.
Still, the data from pediatric studies of the nine drugs show "a reasonably consistent signal for risk," said FDA official Thomas Laughren.
The data showed that, for every 100 children or adolescents taking antidepressants, there is a risk that about two or three patients will show increased suicidal behaviors caused by the drugs and not the child's underlying depression, Laughren told the advisory panel.
On the flip side, the data suggest that roughly 25 percent of these 100 patients will get a benefit from taking antidepressants, he stressed. Thus, the use of these drugs by children requires doctors to carefully balance an antidepressant's risks and benefits, he added.
Laughren said that children with major depressive disorders seem most at risk for increased suicidal tendencies, but the suicide risk might also be linked to conditions like obsessive compulsive disorder.
The FDA official indicated that suicidal behaviors or thoughts were identified in pediatric studies of seven of the nine antidepressants, but that the findings varied markedly among individual drugs and particular drug studies.
But it seems clear from the data that the increased suicide tendency is caused from antidepressants as a class, according to Laughren.
The FDA is also seeking advice from the panel on what further studies are needed of antidepressants in children.
Only Prozac is currently approved by the FDA to treat depression in children, but other antidepressants are widely prescribed "off-label" for young patients.
The antidepressants at the center of the inquiry include Bristol Myer Squibb's Serzone, Forest Laboratories' Celexa, GlaxoSmithKline's Paxil and Wellbutrin, Pfizer's Zoloft, Solvay Pharma's Luvox, Organon's Remeron and Wyeth-Ayerst Laboratories' Effexor.
The panel also said Tuesday that it agreed with the way the FDA, working with Columbia University, reclassified suicidal behaviors into standardized definitions.
Because each drug sponsor had used its own definition of what amounted to suicidal behavior when studying its antidepressant in children, it had been harder to clearly link the drugs to increased suicidal behaviors, according to FDA officials.
Panel members said that the FDA's analysis might help drug firms better identify suicidal behaviors in further trials of antidepressants in pediatric patients.
On another point, one panelist accused makers of antidepressants of holding back information about the drugs' risks in children from regulators.
In any case, officials seemed convinced that the increased risk of suicidal tendencies in children is real. See previous story.
Separately, the FDA's Robert Temple told the panel that the agency may start requiring companies to add pediatric studies showing the drug doesn't work in children to their drugs' labeling.
The agency has been reluctant in the past to make companies include negative studies on labels, since one negative study doesn't necessarily mean that drug doesn't work, Temple said, but the agency may reverse that policy for pediatric studies.
The antidepressant link to suicidal behavior prompted a call for firms to make unfavorable studies public by registering the trials in a government database. However, Temple added that his agency might not have the authority to require that studies be published if the study drug does not get approval.
Reviewer Says Depression Drugs, Suicide Linked
Mon Sep 13, 2004 05:47 PM ET
By Lisa Richwine
BETHESDA, Md. (Reuters) - A U.S. government medical reviewer told an advisory panel on Monday new findings confirmed his conclusion months ago that certain antidepressants increase the chances of suicidal behavior among children and teens.
Dr. Andrew Mosholder was prevented from giving his analysis to the panel at a public meeting in February because his supervisors thought the data he relied upon were unclear.
Relatives of suicide victims who took antidepressants applauded when Mosholder began speaking to a Food and Drug Administration advisory panel that is considering whether the drugs should come with stronger warnings.
He told the panel that information from 23 clinical trials of nine different drugs given to children and teens "indicate an association of suicidal (behavior) with antidepressant treatment" over the short term. Studies only lasted as long as 16 weeks, so long-term risks are unknown. The FDA has come under fire for being too slow to recognize the potential hazards. The agency first became aware of a possible link to suicidal behavior among children in May 2003, agency officials said.
"Obviously opinions on this are different," Mosholder told reporters when asked how he felt about being denied the chance to speak publicly earlier.
Another FDA reviewer, Dr. Tarek Hammad, also said the studies reviewed by Mosholder, other FDA staff and Columbia University suggested a link between antidepressant use and suicidal tendencies in youth.
For every 100 patients treated with an antidepressant, two or three might have a higher risk of suicidal behavior, beyond the risk inherent from depression, Hammad estimated.
ANGRY FAMILIES LASH OUT
The advisory panel is considering data from trials of more than 4,000 children with ages ranging from six to 18.
No actual suicides occurred during any of the trials, but there were dozens of reports of suicidal thoughts and actions such as writing suicide notes or attempting overdoses.
Angry relatives of suicide victims lashed out at the FDA for failing to warn about the chances of violent behavior.
"Why haven't parents ... been told the truth about these medications?" asked Mark Miller, who said his 13-year-old son killed himself after starting therapy with Pfizer Inc.'s Zoloft.
"We learned the hard way that these drugs can kill," Miller said.
Back in February, FDA officials said data on a possible link with suicide were too murky to interpret and needed further evaluation.
Dr. Robert Temple, head of the FDA office that reviews antidepressants, said he did not regret seeking the additional perspective, even though the FDA's most recent analyzes support Mosholder's earlier conclusions.
Officials wanted to avoid "scaring people needlessly" from the drugs because they can save lives by preventing suicides caused by depression, Temple told reporters.
The agency now advises doctors and parents to watch for signs of worsening depression or suicidal thoughts in patients taking the newer antidepressants. Drug makers agreed to put that advice on their product labels.
Most of the drugs in question are in a class called selective serotonin reuptake inhibitors, or SSRIs.
Most, however, have not been shown to work for children. Only Eli Lilly and Co.'s Prozac, also sold generically as fluoxetine, is approved for treating pediatric depression.
The committee will meet again on Tuesday to decide whether to recommend stronger warnings or other regulatory steps for some or all of the antidepressants.
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© Copyright Reuters 2004