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To give academic researchers, government officials, and industry scientists an opportunity to assess the state of pediatric psychopharmacology and identify challenges facing professionals in the field. Increased federal spending and the introduction of pediatric exclusivity led to large increases in pediatric psychopharmacology research in the 1990s. Despite the increase in research, concerns exist about methods and incentives for making new medications available for use in pediatric psychiatric disorders. In recognition of these concerns, the Duke Clinical Research Institute held a roundtable in September 2004. Participants from the National Institutes of Health, regulatory agencies, academia, and the pharmaceutical industry spoke about the effects of government regulations such as the U.S. Food and Drug Administration Modernization Act and the Pediatric Research Equity Act on pediatric research from academic, clinical, and industry perspectives, and bioethical considerations of such research. To ensure development of new drugs for treating psychiatric disorders in children and adolescents, we must address the challenges posed by the regulatory environment governing pediatric psychopharmacology research. Strategies were identified for improving the evidence base for psychopharmacologic interventions in youth before widespread use and for more effectively defining a research agenda for the future.

To test whether 12-week treatment of major depression improved the level of functioning, global health, and quality of life of adolescents. The Treatment for Adolescents With Depression Study was a multisite, randomized clinical trial of fluoxetine, cognitive-behavioral therapy (CBT), their combination (COMB), or clinical management with placebo in 439 adolescents with major depression. Functioning was measured with the Children's Global Assessment Scale (CGAS), global health with the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA), and quality of life with the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q). Random-effects regression models were applied to the data. Compared with placebo, COMB was effective on the CGAS (p < .0001), HoNOSCA (p < .05), and PQ-LES-Q (p < .001), whereas fluoxetine was superior to placebo on the CGAS only (p < .05). COMB was superior to fluoxetine on the CGAS (p < .05) and PQ-LES-Q (p = .001). Fluoxetine was superior to CBT on the CGAS (p < .01). CBT monotherapy was not statistically different from the placebo group on any of the measures assessed. Treatment effects were mediated by improvement in depressive symptoms measured on the Child Depression Rating Scale-Revised. The combination of fluoxetine and CBT was effective in improving functioning, global health, and quality of life in depressed adolescents. Fluoxetine monotherapy improved functioning.

While the evidence base for treatments for adolescent depression is building, little is known about the relative efficiency of such treatments. Treatment costs are a relevant concern given the competing demands on family and health care budgets. The authors evaluated the cost-effectiveness of three active treatments among adolescents with major depressive disorder. Volunteers (N=439) ages 12 to 18 with a primary diagnosis of major depressive disorder participated in a randomized, controlled trial conducted at 13 U.S. academic and community clinics from 2000 to 2004. Subjects included those participants who did not drop out and had evaluable outcome and cost data at 12 weeks (N=369). Subjects were randomly assigned to 12 weeks of either fluoxetine alone (10-40 mg/day), CBT alone, CBT combined with fluoxetine (10-40 mg/day), or placebo (equivalent to 10-40 mg/day). Both placebo and fluoxetine were administered double-blind; CBT alone and CBT in combination with fluoxetine were administered unblinded. Societal cost per unit of improvement on the Children's Depression Rating Scale-Revised and cost per quality-adjusted life year (QALY) were compared. Results ranged from an incremental cost over placebo of $24,000 per QALY for treatment with fluoxetine to $123,000 per QALY for combination therapy treatment. The cost-effectiveness ratio for CBT treatment was not evaluable due to negative clinical effects. The models were robust on a variety of assumptions. Both fluoxetine and combination therapy are at least as cost-effective in the short-term as other treatments commonly used in primary care (using a threshold of $125,000/QALY). Fluoxetine is more cost-effective than combination therapy after 12 weeks of treatment.

To ascertain remission rates in depressed youth participating in the Treatment for Adolescents With Depression Study (TADS), a multisite clinical trial that randomized 439 adolescents with major depressive disorder (MDD) to a 12-week treatment of fluoxetine (FLX), cognitive-behavioral therapy (CBT), their combination (COMB), or clinical management with pill placebo (PBO).

The current generation of clinical trials in pediatric psychiatry often fails to maximize clinical utility for practicing clinicians, thereby diluting its impact. To attain maximum clinical relevance and acceptability, the Child and Adolescent Psychiatry Trials Network (CAPTN) will transport to pediatric psychiatry the practical clinical trials model widely used in other areas of medicine. CAPTN, a collaborative effort of the Duke Clinical Research Institute and the American Academy of Child and Adolescent Psychiatry, will conduct large, simple "practical" trials that provide generalizable answers to important clinical questions without bias. "Large" in this case means the random allocation of thousands of patients in hundreds of clinical centers to different treatments as they are delivered in community settings. "Simple" means that the number and type of data elements (and, hence, subject and investigator burden) is small and straightforward so as not to discourage provider or patient participation and to maximize the number of subjects per dollar spent. With 200 to 400 child and adolescent psychiatrists each participating in two or three practical clinical trials over 4 years, CAPTN promises to advance both the evidence base and research capacity in child and adolescent psychiatry.