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Clinical and Research News
New Depression Resources Educate Parents, Physicians
Psychiatric News
Volume 40 Number 5 page 1-42
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APA Trustee David Fassler, M.D. (far right), introduces ParentsMedGuide.org, 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

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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 placebo."

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 powerful undertow."

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 adverse-event reporting.

"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 ideation."

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 attempts."

"ParentsMedGuide," "PhysiciansMedGuide," and related resources are posted at<parentsmedguide.org>.

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APA Trustee David Fassler, M.D. (far right), introduces ParentsMedGuide.org, 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

Anchor for JumpAnchor for Jump

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


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