APA Trustee David Fassler, M.D. (far right), introduces
with (from right to left) Darrel Regier, M.D., APA's director of research;
Gail Griffith, FDA advisory panel member; Leslie Walker, M.D., of the Society
of Adolescent Medicine; Sherri Walton, parent/mental health advocate; and
Darcy Gruttadaro, J.D., director of the NAMI Child and Adolescent Action
Center. David Hathcox
Gail Griffith, the patient representative to the FDA's
Psychopharmacological Drugs Advisory Committee, says that had she known then
what she knows now, she would never have voted in favor of the black-box
warnings. David Hathcox
APA and the American Academy of Child and Adolescent Psychiatry (AACAP)
unveiled a new Web site last month to serve as a primary resource for parents
of children with depression. The highlights of the Web site are two medication
fact sheets: "ParentsMedGuide," which uses basic, straightforward
language for parents and other family members of children and adolescents
being treated for depression, and "PhysiciansMedGuide," which
includes a referenced discussion of the evidence base on the use of
antidepressant medications by primary care and family practice physicians to
treat children and adolescents for depression.
"We've tried to address many of the specific questions we've been
hearing from parents," said David Fassler, M.D., at a press briefing in
Washington, D.C., launching the new resources.
Fassler, a child and adolescent psychiatrist, APA trustee-at-large, and
member of the AACAP Council, chaired the task force of APA and AACAP members
that developed the fact sheets and Web site. The task force worked closely
with family members and advocacy organizations, including the National Mental
Health Association and the National Alliance for the Mentally Ill.
The resources have been approved by the APA Board of Trustees and the AACAP
Council and endorsed by a wide array of patient, family, and professional
organizations (see box on page
42). As Web-based resources, posted at<parentsmedguide.org>,
the guides will be updated periodically as new data become available.
"The fact sheets explain that research has shown that a number of
interventions are effective at treating the signs and symptoms of depression
in children and adolescents," Fassler noted."
ParentsMedGuide" and "PhysiciansMedGuide" also
emphasize that all treatments have risks and benefits, he continued,"
and we believe that parents and physicians deserve as much information
as possible to make appropriate decisions for their children and their
patients. That's why we've developed these fact sheets."
The two med guides include a detailed discussion of the decision by the
Food and Drug Administration (FDA) to implement black-box warnings last fall
on all antidepressants marketed in the United States (Psychiatric
News, November 5, 2004).
"The FDA identified a small increase in the percentage of children
who spontaneously expressed thoughts about suicide or demonstrated potentially
harmful behaviors," Fassler explained. "The data actually show
that in those studies that asked kids about suicidal thoughts, there were no
significant differences between those on medication and those taking a
The need for balanced, accurate information on the risks and benefits of
antidepressants was made all the more evident with the release of updated
prescription sales data the day before the launch of the new Web site. Those
data, spanning 12 quarters from the first quarter of 2002 through the fourth
quarter of 2004, showed dramatic decreases in pediatric antidepressant
utilization, apparently in response to the FDA's advisory committee meetings
and imposition of black-box warnings (see chart on page 1). The data, from a
Medco Health Solutions Inc. analysis, show an overall 10 percent decrease in
the proportion of patients under age 18 on an antidepressant in 2004, in sharp
contrast to the nearly 9 percent increase during 2003.
Usage of the drugs in pediatric patients had steadily been on the increase
through all four quarters of 2002. However, with the first quarter of 2003,
that trend began to change as the quarter-to-quarter increases that had been
common became ever smaller. In the first quarter of 2004—at the same
time as the FDA's first advisory committee meeting on antidepressants and
suicidality—usage declined by 9.4 percent compared with the first
quarter of 2003. The most dramatic declines were registered in the third and
fourth quarters of 2004, when the FDA held its second set of advisory
committee hearings and ordered the strong warnings.
However, the Medco Health data also reveal that, on the whole,
antidepressants are prescribed to a very small proportion of eligible patients
under the age of 18 and thus strongly suggest that undertreatment continues to
be a significant dilemma.
For example, during the three years the data cover, the fourth quarter of
2002 saw the highest number of patients under 18 receive prescriptions for
antidepressants: 103,102 out of a total of 12,374,932 patients under 18
covered by Medco. That amounts to a prescribing rate of only 0.83 percent.
Over the 12 quarters of data released by Medco Health, prescribing rates
ranged from a low of 0.66 percent to a high of 0.84 percent—far below
the expected incidence of depression in the population (between 3 percent and
5 percent, according to the NIMH).
"I had grave misgivings about imposing a black-box warning on all
antidepressants because the repercussions of that action will be incalculable
for years to come," said Gail Griffith, the patient representative on
the FDA's Psychopharmacological Drugs Advisory Committee. That committee and
the Pediatric Drugs Advisory Committee voted for the warnings.
Griffith, who attended the press briefing launching the pair of med guides,
has long grappled with depression herself, she said, and has a son who
attempted suicide amid a severe depression at the age of 16.
"If I would have known how sharply prescription rates were
falling," Griffith added, "I would not have voted in favor of the
black-box warning. I had hoped the FDA could help to inform parents, but it
seems many parents have simply become fearful of antidepressants, which so
often are the lifejacket preserving us from being sucked under by depression's
APA research staff reviewed the evidence base relating antidepressants and
suicidal thoughts and behaviors in preparation for developing the fact sheets
and Web site. It quickly became apparent that part of the difficulty in
analyzing the FDA's position was the agency's narrow focus on spontaneous
"We wanted to focus on the broader context," explained Darrel
Regier, M.D., M.P.H., director of research at APA and executive director of
the American Psychiatric Institute for Research and Education. "The FDA
was focusing on a very narrow and specific issue: adverse events that are
spontaneously reported by patients in a clinical trial. The problem we had was
that [the FDA's approach] missed a much larger picture that we think is
important for parents and physicians to understand."
The experience of suicidal thoughts, Regier explained, "is one of the
characteristics of depression. And it is not surprising then that you would
have [a high percentage] of patients who meet criteria for depression also
have, as a part of meeting that criteria, the presence of suicidal
While spontaneously reported events involving suicidal thoughts or
behaviors do occur at a higher rate in those taking medication than in those
on placebo within the context of clinical trials, Regier said, this narrow
focus misses the much larger picture.
The problem, both Fassler and Regier explained, is that systematic
assessment of suicidal thoughts and behaviors—actually asking youngsters
in clinical trials about suicidal thoughts and behaviors—shows no
difference between patients on drug compared with placebo. The FDA noted this
finding in its analysis, but only briefly, and did not discuss it at all at
the public advisory committee meetings.
"We know that the FDA's adverse-event reports are just the tip of the
iceberg of suicidality," Regier continued. "We know that
systematic assessment finds much higher rates and is certainly preferable from
a research standpoint. Children don't often say anything spontaneously about
suicidal thoughts—and it is when they don't talk about it that they are
at gravest risk."
Antidepressant medications, Regier noted, "seemingly allow people to
be more communicative about suicidal ideation," and this may be what is
reflected in the clinical trials data.
"But there is certainly a research issue here regarding what is the
best predictor of not simply suicidal thinking or suicide attempts, but of
completed suicide," Regier said. "We need research to evaluate the
value of spontaneously reported events versus systematic assessment. We need
to recognize that suicide itself is not equivalent to suicidal thoughts or
"ParentsMedGuide," "PhysiciansMedGuide," and
related resources are posted at<parentsmedguide.org>.▪