This six-site parallel RO1 application requests funding for a three year study of the efficacy and safety of methylphenidate (MPH) in preschool children with Attention-Deficit/ Hyperactivity Disorder (ADHD). Although MPH's use in all age groups is increasing, its package insert prohibits its use in preschool children. Previous MPH preschool treatment studies have few subjects, and their results cannot be combined to yield needed safety information. The proposed study will address these concerns by mounting a six-site, controlled trial of 44 ADHD children per site, or 264 children total. It will be based at the New York State Psychiatric Institute (NYSPI), Duke University, Johns Hopkins University (JHU), New York University (NYU), University of California at Los Angeles (UCLA), and University of California at Irvine (UCI). Each site's subjects (N=44) will include: Group 1, ADHD preschoolers (n=33), ages 3-5 years, 6 months; and Group 2 (n=11), a contrast ADHD group, ages 6-8. After assessment, all children will enter a four-part study. Phase l will be a 3 week, open-label safety titration trial of MPH, 2.5 - 10 mg/dose, given 3 times daily (t.i.d.). Those without impairing side effects will enter Phase 2, a five week double-blind, placebo controlled, titration trial, with random assignments (weekly) to either placebo or to one of 4 doses of MPH (2.5, 5, 7.5, and 10 mg/dose) and monitored once in a laboratory (analog) classroom. Phase III will be an open-label, one-year extension, and Phase IV will be a double-blind, placebo discontinuation trial.
Aim I is to determine the safety and efficacy of MPH in preschoolers with ADHD.
Aim 2 is to test for differences between Groups 1 and 2 in dose-response to MPH.
Aim 3 is to examine if two putative risk loci, the dopamine D4 receptor gene (DRD4) or the dopamine transporter gene (DATI), are associated with ADHD in a family-based association study of parent to child allele transmission, and whether dose response to MPH is related to generic variability at these two loci.
|Vitiello, Benedetto; Lazzaretto, Deborah; Yershova, Kseniya et al. (2015) Pharmacotherapy of the Preschool ADHD Treatment Study (PATS) Children Growing Up. J Am Acad Child Adolesc Psychiatry 54:550-6|
|Riddle, Mark A; Yershova, Kseniya; Lazzaretto, Deborah et al. (2013) The Preschool Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS) 6-year follow-up. J Am Acad Child Adolesc Psychiatry 52:264-278.e2|
|Ghuman, Jaswinder K; Riddle, Mark A; Vitiello, Benedetto et al. (2007) Comorbidity moderates response to methylphenidate in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS). J Child Adolesc Psychopharmacol 17:563-80|
|Abikoff, Howard B; Vitiello, Benedetto; Riddle, Mark A et al. (2007) Methylphenidate effects on functional outcomes in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS). J Child Adolesc Psychopharmacol 17:581-92|
|Swanson, James M; Moyzis, Robert K; McGough, James J et al. (2007) Effects of source of DNA on genotyping success rates and allele percentages in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS). J Child Adolesc Psychopharmacol 17:635-46|
|Vitiello, Benedetto; Abikoff, Howard B; Chuang, Shirley Z et al. (2007) Effectiveness of methylphenidate in the 10-month continuation phase of the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS). J Child Adolesc Psychopharmacol 17:593-604|
|Wigal, Tim; Greenhill, Laurence; Chuang, Shirley et al. (2006) Safety and tolerability of methylphenidate in preschool children with ADHD. J Am Acad Child Adolesc Psychiatry 45:1294-303|
|McGough, James; McCracken, James; Swanson, James et al. (2006) Pharmacogenetics of methylphenidate response in preschoolers with ADHD. J Am Acad Child Adolesc Psychiatry 45:1314-22|
|Swanson, James; Greenhill, Laurence; Wigal, Tim et al. (2006) Stimulant-related reductions of growth rates in the PATS. J Am Acad Child Adolesc Psychiatry 45:1304-13|
|Kollins, Scott; Greenhill, Laurence; Swanson, James et al. (2006) Rationale, design, and methods of the Preschool ADHD Treatment Study (PATS). J Am Acad Child Adolesc Psychiatry 45:1275-83|
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