op Food and Drug Administration officials
admitted yesterday that they barred the agency's top expert from
testifying at a public hearing about his conclusion that
antidepressants cause children to become suicidal because they
viewed his findings as alarmist and premature.
"It would have been entirely inappropriate to present as an
F.D.A. conclusion an analysis of data that were not ripe," Dr.
Robert Temple, the Food and Drug Administration's associate director
of medical policy, said in an interview. "This is a very serious
matter. If you get it wrong and over-discourage the use of these
medicines, people could die."
Dr. Temple was seeking to quell a growing controversy into
whether the agency's warnings on March 22 that antidepressant
therapy could lead patients to become suicidal were sufficient.
"There is concern that we hid data," said Dr. Temple. "We did not
hide data. It was there for all to see."
Recent studies have shown that children given antidepressants are
more likely to become suicidal than those given placebos. But the
studies have lead to different interpretations by psychiatrists. The
refusal by drug companies to publish the studies has worsened the
confusion. Internal agency documents obtained by The New York Times
show that federal health officials are divided, too.
Dr. Andrew D. Mosholder, an agency epidemiologist, was the man
charged with analyzing 22 studies involving 4,250 children and seven
drugs. In a carefully argued, 33-page memorandum, he concluded that
children given antidepressants were almost twice as likely as those
given placebos to become suicidal.
He urged the agency to discourage doctors from prescribing to
children all antidepressants except Prozac. Prozac is the only
antidepressant proven effective in treating depressed children, and
its studies showed no link with suicide, Dr. Mosholder wrote. Dr.
Mosholder's conclusions mirrored those made by British health
But Dr. Mosholder's supervisors, Drs. Mark Avigan and Anne
Trontell, wrote memorandums disagreeing, according to the documents.
"In particular, we disagree that the data are sufficiently robust
to advocate preferential use" of Prozac in children, Dr. Trontell
Health officials convened a special advisory committee on Feb. 2
to offer guidance on how the agency should respond to the studies.
As the agency's principal reviewer, Dr. Mosholder was scheduled to
speak. He was removed from the agenda, Dr. Temple said.
Senator Charles E. Grassley, a Republican from Iowa and chairman
of the Senate Finance Committee, said he was investigating whether
the agency inappropriately suppressed crucial findings.
Representative Joe L. Barton, a Republican from Texas who is
chairman of the House Energy and Commerce Committee, said he was
"It would have been very wrong for the F.D.A. to withhold any
information it had about unintended consequences that might result
from the use of antidepressants, especially for children and
adolescents," Mr. Grassley said.
Dr. Temple was unapologetic about the decision.He said that Dr.
Mosholder's underlying data were presented to the committee but that
agency officials explained that Dr. Mosholder had failed to treat
with the appropriate skepticism some reports of suicidal behavior.
The Food and Drug Administration has hired investigators at
Columbia University to examine reports from about 400 of the 4,250
children and determine independently which should be classified as
The controversy had its start when GlaxoSmithKline sought a
six-month extension to its patents on Paxil. To help guide
pediatricians' prescribing habits, federal law grants such
extensions when companies test their medicines in children.
The company's studies in depressed children failed to show any
positive effect. It was a disappointing finding, but patent
extensions are granted even when studies fail. Reviewing the data,
Dr. Mosholder noticed in October 2002 that they showed a disturbing
number of problems listed under the category, "emotional liability."
Suicidal thoughts and self-injurious behavior were among the things
lumped into this category. Dr. Mosholder asked GlaxoSmithKline to
provide more detail about these cases, according to one of the
In May 2003, the company submitted a new report. It showed that
children given Paxil were more likely to become suicidal than those
given placebos. In June, the agency announced that doctors should
avoid using Paxil in depressed children.
Three days later, according to documents and interviews, the
agency asked for similar data from the makers of Prozac, Zoloft,
Luvox, Celexa, Wellbutrin, Effexor, Serzone and Remeron.
Dr. Mosholder found that 108 of the 4,250 children had done
something that merited being called suicidal. He divided the cases
into those who were given drugs and those given placebos and found
that children given drugs were almost twice as likely to become
suicidal as those given placebo.
The agency declined to make Dr. Mosholder available for an