eeding the recommendation of an advisory
committee, the Food and Drug Administration ordered pharmaceutical
companies yesterday to add strong warnings to antidepressants,
saying the drugs could cause suicidal thoughts and actions in some
children and teenagers.
The so-called black-box warnings will appear in boldface type,
framed by a black border, on information sheets for patients and
doctors. They are the toughest requirement that federal drug
regulators can impose short of banning a medication.
Black-box warnings accompany hundreds of other drugs. But in this
case the agency also directed the manufacturers to print and
distribute medication guides with every antidepressant prescription,
to inform patients of the risks. Such guides are required for fewer
than 30 other drugs.
The agency's decision came after a year of intense controversy
about antidepressants and one month after the advisory committee
concluded that evidence linking them with suicidal behavior in
children and adolescents was sufficient to warrant the strengthened
warnings.
Though the overall risk of suicide is low, children and teenagers
who take antidepressants appear twice as likely as those given
placebos to become suicidal, according to studies. If 100 patients
are given the drugs, 2 or 3 more will become suicidal than would
have had they been given placebos, the studies suggest.
Many critics of the drugs said they were pleased by the agency's
action.
"This is a milestone that a lot of us were concerned would never
happen," said Karen Barth Menzies, a plaintiffs' lawyer who
testified at hearings that the advisory committee held on the
drugs.
But she and others said the agency had been too slow to act, and
some said the warnings did not go far enough. Tom Woodward, whose
17-year-old daughter committed suicide last summer, a week after
starting therapy with the antidepressant Zoloft, said she might
still be alive had the F.D.A. acted earlier.
"How many other lives have been lost while they dragged their
feet?" Mr. Woodward asked.
For its part, the American Psychiatric Association, the
specialty's medical society, issued a statement repeating its "deep
concern that a black-box warning on antidepressants may have a
chilling effect on appropriate prescribing for patients."
"This,'' the statement continued, "would put seriously ill
patients at grave risk."
Psychiatrists across the country have been deeply divided about
how to respond to the revised view of antidepressants. Many maintain
that untreated depression poses a far graver risk of suicide in
children and teenagers than the risk posed by the drugs. The number
of teenagers and children being prescribed antidepressants in the
United States has dropped 18 percent this year amid concerns over
the antidepressants, according to a large provider of drug
benefits.
Still, many psychiatrists were pleased that federal drug
regulators were ending the uncertainty surrounding the medicines.
The black-box warning "is probably a little overcautious, but you
have to start somewhere," said Dr. Laurence Greenhill, a professor
of clinical psychiatry at Columbia University.
The warnings will be added to all antidepressants, not just to
the newer generation of drugs that has been a focus of much of the
controversy. The agency has yet to make final the language of the
patient medication guides, but the wording of the black-box warning
is stark.
"Antidepressants increase the risk of suicidal thinking and
behavior (suicidality) in children and adolescents," the warning
begins. It goes on to recommend that patients given the pills be
closely observed, and notes that few antidepressants have proved
effective against depression in children and teenagers.
The agency's action will most likely have a chilling effect on
antidepressant advertising. So-called reminder ads - advertising
that includes only a drug's name and not its use - will be banned
for antidepressants. In other ads, the entire black-box warning must
be either prominently printed on the ad or, for radio and
television, spoken clearly during the commercial.
Dr. Joseph Feczko, president for development at Pfizer Inc.,
which makes Zoloft, said his company was still studying how the
warning would affect its advertising plans for the drug.
Dr. Feczko noted that no completed suicides had been found in any
of the tests of antidepressants in the young. He said Pfizer stood
behind the safety of Zoloft, the biggest-selling antidepressant.
F.D.A. officials and drug company representatives said that to
provide the patient medication guides ordered by the agency,
manufacturers would have to change their packaging processes
entirely.
At present, most antidepressants are delivered to pharmacies in
large plastic containers from which pharmacists count out pills into
the familiar generic plastic vials. But in the coming months,
manufacturers must instead begin delivering them in individually
boxed bottles with patient guides inserted, similar to the way
over-the-counter drugs like Advil and Tylenol are packaged.
Having to stock such bottles will be difficult for some
pharmacies and could lead to confusion, said John Coster, a
spokesman for the National Association of Chain Drug Stores.
Pharmacists will have to devote considerable shelf and inventory
space to storing scores of boxes of antidepressants, Mr. Coster
said. And because the bottles will probably contain 30 pills each,
he added, physicians will be unable to write prescriptions for, say,
20 pills or 40 pills.
"Up and down the distribution line,'' he said, "there's going to
have to be huge adjustments.''
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