FDA of Failing Act on Information About Link Between
Antidepressants, Suicide Risk in Children, Say
Lawmakers27 Sep 2004
could make a decision within days on whether to adopt an
advisory panel's recommendations to include a black box
warning about the increased risk of suicidal tendencies that
antidepressants pose for children, and any labeling changes
could be implemented "in a couple of weeks," Dr. Robert
Temple, director of FDA's office of medical affairs, said
Thursday at a House Energy and Commerce Oversight and
Investigations Subcommittee hearing, the Wall Street Journal
reports (Wilde Mathews, Wall Street Journal, 9/24).
The advisory panel on Sept. 14 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. A black box warning is a
black section with white writing that appears at the top of
drug inserts distributed to physicians and patients.
On Sept. 13, 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 (Kaiser Daily Health Policy Report, 9/15).
FDA regulators are still weighing whether to require a
black box warning or a bolded warning about the drugs'
heightened suicidality risk in children, Temple said (Mulkern,
Denver Post, 9/24).
"My guess is that we probably
will" decide to use a black box warning, Temple added (Harris,
New York Times, 9/24).
In addition, the agency is
still considering whether to add a statement to antidepressant
labels that indicates studies in children found most of the
drugs are no more effective than placebos, the Washington Post
reports (Vedantam, Washington Post, 9/24).
to Temple, FDA is "clearly going to implemen[t]" all the
advisory panel's other recommendations, such as a requirement
that patient information guides be distributed with
antidepressant prescriptions (Wall Street Journal, 9/24).
FDA Officials Asked Mosholder To Modify Documents
According to documents released Thursday at the
day-long hearing, FDA officials instructed agency medical
officer Dr. Andrew Mosholder to delete from records he was
submitting to Congress his research material that showed an
increased risk of suicidality in children who took
antidepressants and told him to conceal the deletions. Panel
members "repeatedly accused the agency of obfuscating the
risks, slowing action and subjecting Mosholder to harassment,"
the Post reports (Washington Post, 9/24).
FDA officials acknowledged that agency managers did not allow
Mosholder to testify at a February public hearing about a
report he compiled that found antidepressants may lead to
suicidal behavior in children because they considered the
Mosholder's 33-page report, based
on an analysis of 22 studies that involved 4,250 children and
seven antidepressants, found that children who took the
medications were twice as likely as those who took placebos to
However, FDA officials raised some
concerns about how Mosholder classified suicidal behavior in
the report. House and Senate Republican leaders at the end of
March launched investigations into whether FDA managers
prevented the release of the report (Kaiser Daily Health
Policy Report, 9/14).
Senate Finance Committee Chair Charles Grassley (R-Iowa)
requested a copy of Mosholder's records for the investigation,
Donna Katz of FDA's Office of Chief Counsel "urged him to
delete material" from a sworn statement about his findings
that also indicated he had been targeted by an internal
inquiry, according to the Post.
FDA's Office of
Internal Affairs, which conducts internal investigations, told
Mosholder that he could be subject to disciplinary action and
questioned him about whether he had leaked his findings to the
news media. Mosholder declined to make the requested changes
to his statement, saying that they would be tantamount to
FDA officials said the deletions were
necessary because agency rules require that internal
investigations remain secret (Washington Post, 9/24).
An FDA spokesperson said the revised version of the
document did not "differ substantively" from the original.
Mosholder at the hearing testified that in addition to
suggestions that he remove the reference to the investigation,
"at one point, alternative conclusions were offered to me,
which I declined to incorporate into my written document"
(Wall Street Journal, 9/24).
Mosholder said he was
asked to lessen his recommendation that antidepressant use in
children be discouraged and to suggest instead that children
use such medications with caution, the AP/South Florida
Sun-Sentinel reports. However, Dr. Paul Seligman, acting
director of FDA's Office of Drug Safety, said it is routine
for superiors to review research conclusions to ensure they
are supported by evidence, adding, "There was never any
pressure to change what he wrote" (Henderson, AP/South Florida
FDA Criticized for Suppressing
Panel members accused FDA of suppressing
information since 1996 on the increased risks of suicidality
in children using antidepressants and of withholding
information from clinical trials suggesting the drugs are not
effective in children.
"FDA knew about the lack of
efficacy in these clinical trials several years ago, and
nothing has been done to change labels to inform doctors,
patients and parents," Rep. Greg Walden (R-Ore.) said. In
March 1996, FDA researcher Dr. James Knudsen wrote to an
executive at Pfizer about an apparent "increased frequency of
reports of suicidality in the pediatric/adolescent patients"
who took the company's antidepressant, Zoloft, in clinical
However, Knudsen's supervisor, Dr. Thomas
Laughren, told the hearing that after reviewing the data he
concluded they did not "represent a signal of risk." He added
that there was no reason for a suicidality risk in children on
antidepressants to be on the agency's "radar screen" between
1996 and last year (Shogren, Los Angeles Times, 9/24).
Temple added that suicidality risk in children taking
the drugs "was not an issue that was prominent in our
thinking," adding, "We had never seen a signal for suicidality
in the adult data" (Denver Post, 9/24).
Peter Deutsch (D-Fla.) said, "There is something terribly
rotten at the FDA. No agency charged with protecting public
health should have behaved with such indifference" (Los
Angeles Times, 9/24).
Hinchey Warns FDA Against
Rep. Maurice Hinchey (D-N.Y.) on
Wednesday sent a letter to FDA Acting Commissioner Lester
Crawford alleging that FDA reduced warnings on antidepressants
after sending out an advisory in March warning doctors to look
for increasing signs of depression or suicidal behavior in
antidepressant takers, the Denver Post reports (Mulkern,
Denver Post, 9/23).
In March, FDA issued an advisory
that asked several companies that manufacture 10 different
antidepressants to revise the products' labels to include
detailed warnings about the potential risk of suicidal
tendencies in patients who take the drugs (Kaiser Daily Health
Policy Report, 9/15).
However, according to the Post,
when the proposed label was later sent to the pharmaceutical
companies, FDA had eliminated the line indicating that the
suicidal thoughts or behavior "might be a result of drug
therapy" and instead included a line that said patients can
worsen "whether or not they are taking antidepressant
medications." Steven Galson, acting director of FDA's center
for drug evaluation and research, said, "What was added in was
more precise. The overall meaning absolutely isn't different."
However, in his letter, Hinchey said that it is
"important to determine why this label was weakened to ensure
that it does not happen again." In an interview, Hinchey said
that he is concerned that FDA's past actions indicate it could
undermine a recent FDA advisory committee recommendation to
require pharmaceutical companies to place black box warnings
on antidepressants (Denver Post, 9/23).
Times Examines Parents' Role
The Los Angeles Times on
Thursday examined how parents' actions helped encourage FDA to
take action on the use of antidepressants by children.
The Times profiled Mark Miller, whose 13-year-old son
committed suicide soon after first taking the antidepressant
Zoloft. Miller's Web site, devoted to the risk of
antidepressants, brought together a number of parents with
similar stories, and together they lobbied Congress to act on
the problem. In February, a number of parents testified at an
FDA advisory panel in Bethesda, Md., and the Times reports
that their stories "helped persuade the panel to urge [FDA] to
warn doctors about the risk of suicide."
said they feel vindicated by the black box advisory issued by
FDA last week but add that they will continue to "press the
FDA to extend the warnings to adults and to add a warning that
the drugs cause some people to become hostile or even
homicidal," according to the Times (Shogren, Los Angeles
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