Pediatricians and Antidepressant Medications: Black Box or Black Hole?

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Joel B. Greenhouse, PhD

Department of Statistics Carnegie Mellon University Pittsburgh, PA 15213

Kelly J. Kelleher, MD, MPH

Office of Clinical Sciences

Columbus Children’s Research Institute The Ohio State University

Columbus, OH 43205

ACKNOWLEDGMENTS

This work was supported by National Institute of Mental Health grants MH66960, MH 65430, and MH30915. The order of the author listing was determined alphabetically.

REFERENCES

1. Leslie L, Newman TB, Chesney PJ, Perrin JM. The food and drug admin-istration’s deliberations on antidepressant use in pediatric patients. Pe-diatrics.2005;116:195–204

2. Hammand TA. Review and evaluation of clinical data: results of the analysis of suicidality in pediatric trials of newer antidepressants. Pre-sented at: Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and Pediatric Advisory Committee; September 13–14, 2004; Bethesda, MD. Available at: www.fda.gov/ohrms/dockets/ac/04/ briefing/2004 – 4065b1.htm

3. Rothwell R. External validity of randomised controlled trials: “to whom do the results of this trial apply?” Lancet.2005;365:82–93

4. Valuck RJ, Libby AM, Sills MR, Giese AA, Allen RR. Antidepressant treatment and risk of suicide attempt by adolescents with major depres-sive disorder: a propensity-adjusted retrospective cohort study. CNS Drugs.2004;18:1119 –1132

5. Spiegelhalter D, Abrams KR, Myles JP.Bayesian Approaches To Clinical Trials And Health-Care Evaluation. Chichester, United Kingdom: John Wiley & Sons; 2004

6. Eddy DM, Hasselblad V, Shachter R. Meta-analysis by the Confidence Profile Method: The Statistical Synthesis of Evidence. New York, NY: Aca-demic Press; 1992

7. Droitcour J, Silberman G, Chemlimsky E. Cross-design synthesis: a new form of meta-analysis for combining results from randomized clinical trials and medical-practice databases.Int J Technol Assess Health Care.

1993;9:440 – 449

Pediatricians and Antidepressant

Medications: Black Box or Black

Hole?

ABBREVIATIONS. AAP, American Academy of Pediatrics; FDA, US Food and Drug Administration; AACAP, American Academy of Child and Adolescent Psychiatry.

T

he intent of this commentary on the article by

Leslie and colleagues1 _{is to describe ongoing}

efforts by the American Academy of Pediatrics (AAP) and other pediatric professional organizations

to support pediatricians and other pediatric clini-cians as they attempt to provide care for their pa-tients who have mental health disorders.

The article by Leslie et al is extremely important to primary pediatric medical providers and provides an important framework for this commentary for sev-eral reasons.

• Although there have been periodic short articles published (eg, ref 2_{), this article responds to}

re-quests from pediatricians for a more comprehen-sive summary of information describing the US Food and Drug Administration (FDA) review of antidepressant use in US children.

• The authors provided the background information

of the uneven published evidence of children’s responses and observed adverse effects of antide-pressants.

• Progressive regulatory steps were described, most of which have occurred in the past 10 years. • The need for additional research is raised. Kelleher

and Greenhouse’s commentary3_{expands the}

dis-cussion. The studies advocated by Kelleher and Greenhouse are essential to the “do-no-harm” dic-tum guiding the pediatrician’s daily work.

• The authors grappled with the thorny issue of

“off-label” prescribing of antidepressants and pro-posed future activities needed to establish the safe and appropriate prescribing patterns pediatricians want to follow.

THE PRIMARY CARE PROVIDER ON THE FRONT LINE

The AAP recognizes the critical importance of pro-viding pediatricians with assistance in the pharma-cological management of children and adolescents with mental health disorders. The FDA Pediatric Ad-visory Committee’s vote in September 2004 to advise the FDA to require a “black-box warning” sounded an alarm extending from the examination rooms of tertiary child psychiatry clinics in Boston, Massachu-setts, to solo primary care providers in the Oklahoma panhandle and rural Montana. Pediatricians were left wondering what to do about their patients al-ready taking antidepressants (for a variety of condi-tions, as Leslie and her colleagues note). Many of these children had dramatic improvement in the quality of their daily life experiences and showed no evidence of suicidal thinking, let alone self-destruc-tive actions. Would it be more “harmful” to with-draw the medications from their treatment programs than it would be to continue prescribing these black-box medications? What discussions should ensue be-tween the physicians and the parents of these chil-dren? Additionally, should these medications be prescribed as part of a newly identified mental health condition? Were there new expectations for informed consent and monitoring? What would be the future implications for other psychotropic medi-cations prescribed for children (eg, the stimulant medications)?

Now, 8 months later, pediatricians grapple with these and additional issues. In an unusual step, the FDA has released suggested practice parameters for

Accepted for publication Apr 26, 2005. doi:10.1542/peds.2005-0928

No conflict of interest declared.

Address correspondence to Lynn Mowbray Wegner, MD, Learning and Development Associates, 3500 Gateway Centre Blvd, Suite 140, Morrisville, NC 27560. E-mail: lwegner@learningfirst.com

COMMENTARIES 233

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monitoring youth taking antidepressants and raised concerns about medico-legal implications of care provision. The suggestion to limit the use of psych-otropic medications in the United States solely to mental health subspecialists (eg, child and adult psy-chiatrists, pediatric subspecialists with postresidency training in mental health diagnosis, management, and psychotropic medications) is untenable, given the projected increase in incidence of the disorders and the concomitant static numbers of child psychi-atrists.4

Leadership of national pediatric medical organiza-tions recognizes improved access to mental health care must involve children’s medical primary pro-viders. We now have a situation in the United States in which screening is encouraged in primary care settings to identify children and adolescents with needs for developmental and/or emotional/behav-ioral assessment and to provide possible interven-tion.5 _{What steps are the AAP and other pediatric}

organization taking to assist the primary care front line?

CURRENT AAP ACTIVITIES RESPONDING TO THE BLACK BOX

Leslie and her co-authors articulated important areas for development. At this time, the following are in place:

Coordinated Activities Within the AAP Regarding the Black-Box Warning

When the FDA announcement was made last fall, the leadership of the AAP Section on Developmental and Behavioral Pediatrics, Committee/Section for Children With Disabilities, Committee on Drugs, Committee on Psychosocial Aspects of Child and Family Health, Committee on Medical Liability, AAP Federal Affairs Office, and several AAP members attending the FDA hearings began an ad hoc group: the “black-box committee.” Regular conference calls were established immediately after the FDA an-nouncement. Since then, antidepressant use as well as other emerging psychotropic medication issues (eg, the Drug Enforcement Agency announcement regarding schedule II drugs–refill practice, the Cana-dian government’s announcement of the prohibition against prescribing long-acting amphetamine salt medications) have been discussed. The black-box committee is in the midst of finalizing suggestions to help primary medical providers. These suggestions will be forthcoming in the next 2 months (possibly sooner) and will provide interim guidance between the 2004 FDA decision and the future development of a set of consensus-supported practice guidelines.

Development of Materials for Use With Families in Primary Care Settings

In late December, the joint American Academy of Child and Adolescent Psychiatry (AACAP)/Ameri-can Psychiatry Association sent their preliminary guidelines and proposed a “family fact sheet”6_{to the}

AAP (among other organizations) for review and anticipated endorsement. The AAP board felt that a

separate family fact sheet endorsed by the AAP would better meet the needs of primary pediatri-cians. The AACAP statement to psychiatrists and the family fact sheet were subsequently published in February 2005 on the AACAP Web site and a Web site directed at the lay public. The black-box commit-tee is revising this statement so that it is more ap-propriate for use in primary care settings. The ex-planatory statement for families, the “AAP Family Fact Sheet,” should be released by the black-box committee in the next several months. AAP member-ship will be alerted on the AAP Web site and other AAP-sponsored periodicals such as the AAP News. This fact sheet will not be identical to the AACAP family information sheet.

Improved Partnerships With Child Psychiatry at the National Level

Two national organizations, the AAP and AACAP, are combining forces to create the support permitting primary providers to function as the “front line.” Carol Berkowitz, MD, FAAP, and Richard Sarles, MD, both current presidents and representing the leadership of the AAP and AACAP, respectively, met in January 2005 and jointly endorsed future col-laborations between pediatrics and child psychiatry to enhance access to and quality of children’s mental health care. Efforts at increasing AAP/AACAP col-laboration have continued. Drs Berkowitz and Sarles sent a joint letter to a national behavioral health company endorsing modification of allowable phy-sician visits for medication monitoring in light of the FDA decision. There have been official AACAP rep-resentatives on AAP projects, and new relationships are being established. For example, an AAP liaison to the AACAP Committee on Healthcare, Access, and Economics was created to specifically collaborate on access areas through identifying effective collabora-tions between primary care physicians and child psy-chiatrists as well as improving financial factors. The AAP and AACAP are also addressing access-to-care issues in the areas of reimbursement, mental health “carve outs,” accurate coding for mental health is-sues, and novel collaborative working relationships to extend the limited US child psychiatry workforce.

Development of Continuing Education Modules for the Primary Care Provider

AAP continuing medical education meetings are being developed to provide sessions describing evi-dence-based care and consensus positions on the diagnosis and management of children’s and adoles-cents’ mental health disorders. Articles in AAP-spon-sored publications will continue to expand the knowledge base for primary providers for children. The evidence supporting intervention (both pharma-cologic and nonpharmapharma-cologic) will be clearly iden-tified in all continuing medical education activities. The AAP will continue to require full disclosure of pharmaceutical industry relationships for those pre-senting programs at these meetings and writing these articles. In addition, the Section on Develop-mental and Behavioral Pediatrics will continue to host 4-day-long continuing medical education

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ing in developmental and behavioral diagnosis and management on an every-other-year basis.

Advocacy for Research on Pediatric Use of Psychotropic Medications

AAP members of FDA panels will continue to advocate for additional studies of the long-term ef-fects of psychotropic medications and children’s ex-posure to existing medications. Improved under-standing of the metabolism of these medicines is essential to completely understanding children’s re-sponses to them.

Support for the Primary Care Provision of Children’s Mental Health Care in General

The AAP Board established the Task Force on Mental Health in 2004 with representation from many areas of the AAP (including AAP board rep-resentation) and liaisons from the AACAP, Ameri-can Psychological Association, National Association of Social Workers, National Association of Mentally Ill, Child and Adolescent Action Center, Child Neu-rology Society, and the Society for Adolescent Med-icine. The Task Force on Mental Health has initial 2-year funding (with grant applications pending for additional years) to develop a practical consensus-based approach for the primary care provider to identify and establish an initial treatment program for children and adolescents in their practice. Estab-lishing collaborative community-based relationships with other mental health providers will be a very important component.

WHAT THE PRIMARY PROVIDER CAN DO TODAY

Although the proposed documents described above are being developed, primary health providers have a responsibility to heed the recommendations by Leslie et al:

• Pediatricians must know the published evidence

for those mental health conditions in children showing positive response to medications. • Local community resources should be identified to

provide appropriate nonpharmacologic treatment (eg, family therapy, cognitive behavioral therapy, interpersonal therapy).

• Diagnostic assessments should include

standard-ized rating scales supporting the appropriate Di-agnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis. (For examples of scales, see www.brightfutures.org/mentalhealth and the Center for Epidemiologic Studies Depression Scale for Children [CES-DC], and the Pediatric Symp-tom Checklist [PSC, Y-PSC] at www.dbpeds.org.) • Regular monitoring of efficacy and adverse effects must be part of the comprehensive plan. Standard-ized rating scales may be a useful part of this efficacy surveillance. The individual patient’s con-dition will indicate the need for the specific com-bination of telephone and face-to-face contacts. The prescribing physician needs to pay particular attention to the initiation, titration, and

discontin-uation periods with respect to medication

management.

Parents depend on pediatricians to advise treat-ment based on knowledge, and pediatricians expect the AAP to provide informed guidance. Both needs can, and will, be met.

Lynn Mowbray Wegner, MD

Learning and Development Associates Morrisville, NC 27560

REFERENCES

1. Leslie L, Newman TB, Chesney PJ, Perrin JM. The food and drug admin-istration’s deliberations on antidepressant use in pediatric patients. Pe-diatrics.2005;116:195–204

2. Wegner L. Advice for treating children with antidepressants.AAP News.

2004;25:289

3. Kelleher KJ, Greenhouse JB. Thinking outside the (black) box: antide-pressants, suicidality, and research synthesis.Pediatrics.2005;116:231–233 4. American Academy of Child and Adolescent Psychiatry. AACAP work force data sheet. Available at: www.aacap.org/training/workforce.htm. Accessed April 15, 2005

5. Rezet B, Risko W, Blaschke GS; Dyson Community Pediatrics Training Initiative Curriculum Committee. Competency in community pediatrics: consensus statement of the Dyson Initiative Curriculum Committee.

Pediatrics.2005;115(4 suppl):1172–1183

6. American Academy of Child and Adolescent Psychiatry. Facts for fam-ilies. Available at: www.aacap.org/publications/factsfam/index.htm. Accessed April 15, 2005

Screening for Overweight in

Children and Adolescents:

Where Is the Evidence?

A Commentary by the Childhood

Obesity Working Group of the US

Preventive Services Task Force

ABBREVIATION. USPSTF, US Preventive Services Task Force*.

T

he prevalence of childhood and adolescent

overweight has tripled over the past 2 decades, and associations have been identified between dietary patterns, physical activity, sedentary behav-iors, and overweight. Some believe that pediatricians can easily recognize an overweight or obese child or adolescent and that there are sufficient therapeutic options to offer these patients and their families.1

However, primary care clinicians face obese and

* The USPSTF is an independent panel of experts in primary care, preven-tion, and behavioral medicine whose charge is to develop recommendations for clinical preventive services based on high-quality evidence.

Accepted for publication Apr 19, 2005. doi:10.1542/peds.2005-0305

Conflict of interest: Dr Teutsch is a Merck & Company, Inc employee and stock options holder.

Address correspondence to Program Director, USPSTF, Agency for Health-care Research and Quality, 540 Gaither Rd, Rockville, MD 20850. E-mail: uspstf@ahrq.gov.

PEDIATRICS (ISSN 0031 4005). Published in the public domain by the American Academy of Pediatrics.

COMMENTARIES 235

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DOI: 10.1542/peds.2005-0928

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