A medical reviewer at the Food and Drug Administration
recommended earlier this year that the agency adopt a tough
"risk management strategy" urging doctors to stop prescribing
most antidepressants to children, but the FDA rejected his
advice and instead asked drug companies only to warn patients
and doctors about possible risks to young patients, The
Chronicle has learned.
Dr. Andrew Mosholder, an epidemiologist in the FDA's Office
of Drug Safety, analyzed 22 clinical trials of nine
antidepressants and concluded that the drugs appeared to
double the risk of suicidal behavior among children. A copy of
his report, obtained by The Chronicle, shows that Mosholder
recommended that the FDA adopt a "risk management strategy
directed at discouraging off-label pediatric use of
antidepressants" other than Prozac in the treatment of
children with depression.
As reported by The Chronicle at the time, Mosholder's
presentation to an FDA advisory committee in February was
removed from the agenda by his superiors at the agency.
The FDA opted not to issue a recommendation to doctors that
they stop prescribing the drugs to children, as British
regulators did last year and as Mosholder had urged. Instead,
the agency took a much milder step last month and called on
drug companies to include warnings in the prescribing
information provided to doctors about the risks of negative
side effects among patients who start taking a drug or
increase its dosage.
The agency also contracted with a group of doctors at
Columbia University to reanalyze the clinical trial data
provided by drug companies, the same data Mosholder reviewed,
to see whether suicidal events were correctly classified.
Agency officials have argued that the data from those trials
are sometimes vague and that some behaviors -- such as a child
slapping herself in the head -- may have been labeled wrongly
as suicidal events by researchers conducting the drug
Committees in both the House and Senate have opened
investigations into the withholding of Mosholder's report and
into efforts by the FDA's Office of Internal Affairs to
identify the staff members who leaked information to The
One congressional source predicted that the investigation
was likely to trigger congressional hearings. "I think
eventually there will be some hearings," the source said.
"There's no way to put a good face on this decision not to
allow Dr. Mosholder to present his conclusions to the advisory
Despite repeated requests, senior FDA officials declined to
comment for this story.
However, in a letter sent Wednesday to House Energy and
Commerce Committee Chairman Joe Barton, R-Texas, an agency
representative defended the agency's decision to keep
Mosholder from presenting his report. Agency officials
"decided that having Dr. Mosholder present his conclusion to
the Advisory Committee, with the appearance that it was an
agency determination, would be potentially harmful to public
health as it might lead patients who were actually benefiting
from the use of these drugs to inappropriately discontinue
therapy," wrote Amit Sachdev, acting associate commissioner
Critics of the FDA's handling of the antidepressant ruling
reacted to details of the Mosholder report with outrage. "It's
astounding that FDA officials actively blocked vital, possibly
life-saving information about the suicide risks to children"
of these drugs, said Vera Sharav, president of the Alliance
for Human Research Protection, an advocacy group. "Every day
that doctors and parents are not informed about the risks,
children are at risk of dying."
In arguing that the agency should take strong action rather
than wait for the reanalysis by the Columbia University group,
Mosholder made much the same point in his report.
"Given the strength of the association shown by the present
data, the clinical importance of the apparent effect, and the
fact that the additional analyses are likely to take several
more months to complete while considerable numbers of
pediatric patients are being exposed to these drugs, I favor
an interim risk management plan," he wrote.
Mosholder's report found that 74 children out of 2,298 who
took antidepressants engaged in a "suicide-related event,"
compared to 34 of the 1, 952 patients who took placebos, or
fake pills. The drugs presenting the highest risk were Effexor
and Paxil, which nearly tripled the risk of a suicidal event,
and Zoloft, which more than doubled the risk, his research
Prozac, which is now available in generic form, had the
lowest risk among the major drugs, and is the only
new-generation antidepressant specifically approved by the FDA
for treating depressed children. For that reason, Mosholder
recommended that Prozac alone continue to be prescribed to
But since drugs that have been cleared by the FDA for
treatment of adults can be prescribed "off label" to children,
other drugs -- including Paxil, Zoloft, Effexor, Luvox,
Remeron, Celexa, Serzone and Wellbutrin -- are widely
prescribed for children and teenagers. The FDA estimates that
nearly 11 million antidepressant prescriptions were written
for children in 2002, 2.7 million of them for children under
Joseph Glenmullen, a clinical instructor in psychiatry at
Harvard University, said the agency's withholding of the
Mosholder report and its failure to take stronger action was
an example of the FDA's failure to protect the public from the
dangerous side effects of antidepressants.
"They have mishandled this issue for 15 years," he said.
"They have not adequately protected American children."