A scientist at the Food and Drug Administration has been
barred from publicly presenting his finding that several
leading antidepressants may increase the risk of suicidal
behaviors among children, according to sources inside the FDA.
FDA medical officer Andrew Mosholder was to present his
report Monday at an FDA advisory hearing in Washington that
promises to be a contentious affair involving competing
medical experts and parents whose children took their own
lives while on the medications.
A senior FDA official said the study wouldn't be presented
because it wasn't "finalized." But critics fear that the
agency's action indicates it is not prepared to take stronger
action against the drugs, despite warnings about their
possible effects on children.
Mosholder had been asked by the agency to perform a safety
analysis of antidepressants after reports emerged this summer
of high rates of suicidal behavior among children enrolled in
clinical trials for Paxil, Effexor and other antidepressants.
Mosholder, a child psychiatrist, reviewed data from 20
clinical trials involving more than 4,100 children and eight
different antidepressants. His preliminary analysis, according
to two FDA sources familiar with the report's contents,
concluded that there was an increased risk of suicidal
behavior among children being treated for depression with
Paxil and several other antidepressants.
An initial agenda for Monday's hearing listed Mosholder and
his findings, but his presentation was removed from a revised
agenda, and Mosholder was told that he could not present his
findings at the hearing, one FDA official, who wished to
remain anonymous, told The Chronicle.
According to the official, in early January, Russell Katz,
director of the division of neuropharmacological drug
products, called Mosholder in for a meeting. "He told him that
he was sorry, but he wasn't going to be able to present (his
report) because he had reached a conclusion and therefore was
biased," the official said.
Mosholder declined several requests to be interviewed and
was not made available despite repeated requests to FDA's
press office. Katz was unavailable to comment on the charges.
In a telephone interview Friday with The Chronicle, Anne
Trontell, deputy director of the agency's Office of Drug
Safety, who is Mosholder's direct supervisor, said the
analysis would not be presented because it had not yet been
approved within her office.
"The consult on that is not finalized. It's not a final
document within the Office of Drug Safety," Trontell said.
However, Trontell said that at Monday's hearing, Mosholder
would provide a rundown of reports of suicidal behavior
received by the agency from doctors and other professionals.
While Mosholder's safety analysis report may eventually be
completed and made public, some FDA insiders fear that
withholding it from Monday's hearing indicates that the agency
may be siding with the pharmaceutical industry in its
long-running battle with critics of antidepressants.
"Why is the agency sitting on its hands and acting as if
there isn't a risk when their own scientists have looked at
the data and concluded that there is?" one FDA official
The use of antidepressants and other psychiatric medication
among children has more than tripled in recent years and now
approaches adult usage rates, according to a January 2003
study in the Archives of Pediatric and Adolescent Medicine.
Study author Julie Zito, an associate professor of pharmacy
and medicine at the University of Maryland, estimates that
more than 1 million American children used antidepressants in
Advocates of the drugs argue that they are imperfect but
necessary weapons against a rising tide of mental illness
Last month, a task force of the American College of
Neuropsychopharmacology released its own preliminary review of
published studies on antidepressants and suicide and stated it
found no statistically significant increase in suicide
attempts among children taking the drugs.
"The most likely explanation for the episodes of attempted
suicide while taking SSRIs (selective serotonin reuptake
inhibitors) is the underlying depression, not the SSRIs," said
Graham Emslie, a child psychiatrist and researcher at the
University of Texas Southwestern Medical Center in Dallas.
But critics, including consumer advocates and mental health
professionals contend, based on other studies, that the drugs
are often ineffective and sometimes dangerous and that the FDA
has failed to vigorously investigate the risks and protect
"The FDA is shielding the industry," said Vera Sharav,
president of the Alliance for Human Research Protection, a
consumer advocacy group.
Mosholder's analysis appears to be similar to the
conclusions reached by British regulators, who told doctors in
December to stop prescribing Paxil, Zoloft, Effexor and three
other antidepressants to children because of an apparent
"increased rate of self-harm and suicidal thoughts."
British regulators took action against Paxil in early June
after new data presented to U.S. and British authorities
showed that children taking the drug were nearly three times
as likely to consider or attempt suicide as children taking
Later that month, the FDA issued a similar warning, urging
doctors not to prescribe Paxil to children and announced that
it would conduct a detailed review of pediatric trials of
Paxil. The review was subsequently broadened to include seven
other antidepressants, including top sellers Prozac, Zoloft
In October, the agency wrote to physicians to "call to
(their) attention" reports of suicide among children in
antidepressant trials. The agency did not, however, urge
doctors to stop prescribing the drugs.
Several current and former FDA staff members interviewed by
The Chronicle said the dispute over Mosholder's report
highlights a lack of assertiveness within the agency over
safety issues. They spoke of a split between the Office of
Drug Safety -- Mosholder's office -- and the FDA's
As an example, they cite a hearing last March on a
rheumatoid arthritis drug, Arava, which had generated numerous
reports of adverse effects, including nine deaths, after being
approved by the FDA.
Members of the Office of Drug Safety, who had prepared a
37-page safety report, were present at the hearing but were
not allowed to speak. A representative of the FDA division
that originally approved the drug, along with the
pharmaceutical company that makes the drug, did most of the
A documentary crew from the PBS series Frontline filmed the
meeting and afterward, in the hallway, caught up with David
Graham, a senior epidemiologist with the Office of Drug
Safety. The producers had been denied previous requests to
interview Graham, but the government scientist gave a brief
interview without permission.
"We had a different perspective, and we really weren't
given an opportunity to present our side of the story,"
Graham, on camera, told the producers. "And the people who did
present, the reviewing division and the company, you know,
they didn't see a problem. This was a very hostile process.
And let's just leave it at that."
Paul Stolley, a professor and former chairman of the
department of epidemiology at the University of Maryland,
spent a sabbatical year as a senior consultant in the Office
of Drug Safety in 2000 and 2001. While there, he recalls, he
tussled with agency managers over the safety of Lotronex, a
drug used to treat irritable bowel syndrome, a chronic but
usually not serious disease.
Stolley said his investigation uncovered high rates of
negative side effects, including a number of deaths, among
patients using the drug and led the company to withdraw the
drug from the market.
A few months later, over Stolley's objections, the agency
allowed the drug back on the market with a "risk management"
program aimed at educating patients and doctors about the
drug's risks. Stolley said he was excluded from internal FDA
meetings on the issue.
"I'm worried about the agency," he says. "I didn't expect
people to think I was right just because I was very senior.
What I did expect was a vigorous debate and instead of having
a vigorous debate, they made a policy decision and then
Rob Waters' article, "A Suicide Side Effect? What
parents aren't being told about their kids' antidepressants,"
appeared in the Jan. 4 edition of The Chronicle Magazine.
E-mail him at firstname.lastname@example.org.