Effects of long-term atomoxetine treatment for young children with attention-deficit/hyperactivity disorder.

OBJECTIVE The purpose of this 13-study (seven double-blind/placebo-controlled, six open-label) meta-analysis is to determine the effectiveness and tolerability of long-term atomoxetine treatment among young children with attention-deficit/hyperactivity disorder (ADHD). METHOD Data were pooled from 6- and 7-year-olds (N = 272) who met DSM-IV criteria for ADHD, received atomoxetine treatment, and were enrolled in clinical trials of > or =2 years. Of these, 97 subjects reached the 24-month time point, providing data for long-term trend analysis of safety and effectiveness. RESULTS Effectiveness for most subjects was maintained over long-term treatment, as demonstrated by total scores and total T scores on the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version, investigator administered and scored. During the 2-year period, 25.7% discontinued because of lack of effectiveness, but adverse events were clinically minor and transient, and only 4.0% of children discontinued because of an adverse event. Notable effects on growth were seen during early phases of the study, with attenuation occurring by the 2-year time point. Statistically significant increases in pulse and blood pressure and decreases in cardiac PR interval were seen, but no changes were deemed both statistically significant and clinically meaningful among any vital signs, electrocardiographic measures, or laboratory tests. CONCLUSION Long-term atomoxetine treatment appears generally well tolerated and effective in the treatment of young children with ADHD.

[1]  M. Horan.  Report of the Second Task Force on Blood Pressure Control in Children--1987. Task Force on Blood Pressure Control in Children. National Heart, Lung, and Blood Institute, Bethesda, Maryland. , 1987, Pediatrics.

[2]  J. Biederman,et al.  Atomoxetine and methylphenidate treatment in children with ADHD: a prospective, randomized, open-label trial. , 2002, Journal of the American Academy of Child and Adolescent Psychiatry.

[3]  P. Muglia,et al.  Long-term risperidone for pervasive developmental disorder: efficacy, tolerability, and discontinuation. , 2000, Journal of child and adolescent psychopharmacology.

[4]  R. Gibbons,et al.  Prevalence rates and correlates of psychiatric disorders among preschool children. , 1996, Journal of the American Academy of Child and Adolescent Psychiatry.

[5]  M. Monuteaux,et al.  PSYCHIATRIC DIAGNOSIS IN PRESCHOOL CHILDREN , 2003 .

[6]  P. Brovedani,et al.  A 3-year naturalistic study of 53 preschool children with pervasive developmental disorders treated with risperidone. , 2003, The Journal of clinical psychiatry.

[7]  S. Faraone,et al.  An open-label, dose-ranging study of atomoxetine in children with attention deficit hyperactivity disorder. , 2001, Journal of child and adolescent psychopharmacology.

[8]  Joseph Biederman,et al.  Psychiatric comorbidity and functioning in clinically referred preschool children and school-age youths with ADHD. , 2002, Journal of the American Academy of Child and Adolescent Psychiatry.

[9]  C. Conners.  Conners' rating scales-revised : technical manual , 1997 .

[10]  S. West,et al.  Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies , 2003, Biological Psychiatry.

[11]  R. Tamura,et al.  A randomized, placebo-controlled study of once-daily atomoxetine in the school setting in children with ADHD. , 2005, Journal of the American Academy of Child and Adolescent Psychiatry.

[12]  C. Popper.  Pharmacological Alternatives to Psychostimulants for the Treatment of Attention-Deficit/Hyperactivity Disorder , 2000 .

[13]  K. Schuh,et al.  Once-daily atomoxetine treatment for children with attention-deficit/hyperactivity disorder, including an assessment of evening and morning behavior: a double-blind, placebo-controlled trial. , 2004, Pediatrics.

[14]  Joel R. Grossbard,et al.  How informative are parent reports of attention-deficit/hyperactivity disorder symptoms for assessing outcome in clinical trials of long-acting treatments? A pooled analysis of parents' and teachers' reports. , 2004, Pediatrics.

[15]  J. Buitelaar,et al.  Relapse prevention in pediatric patients with ADHD treated with atomoxetine: a randomized, double-blind, placebo-controlled study. , 2004, Journal of the American Academy of Child and Adolescent Psychiatry.

[16]  Stephen P. Hinshaw,et al.  A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. , 1999, Archives of general psychiatry.

[17]  A F Roche,et al.  CDC growth charts: United States. , 2000, Advance data.

[18]  L. Greenhill.  The Use of Psychotropic Medication in Preschoolers: Indications, Safety, and Efficacy , 1998, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[19]  Robert Reid,et al.  Adhd Rating Scale-IV: Checklists, Norms, and Clinical Interpretation , 1998 .

[20]  K. Perry,et al.  Atomoxetine Increases Extracellular Levels of Norepinephrine and Dopamine in Prefrontal Cortex of Rat: A Potential Mechanism for Efficacy in Attention Deficit/Hyperactivity Disorder , 2002, Neuropsychopharmacology.

[21]  A. Poulton,et al.  Slowing of growth in height and weight on stimulants: A characteristic pattern , 2003, Journal of paediatrics and child health.

[22]  J. Biederman,et al.  Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder. , 2002, The Journal of clinical psychiatry.

[23]  S. Sandberg.  Epidemiological aspects: what have we learned over the last decade? , 2002 .

[24]  J. Wernicke,et al.  Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study. , 2001, Pediatrics.

[25]  S. West,et al.  Once-Daily Atomoxetine Treatment for Children and Adolescents With Attention Deficit Hyperactivity Disorder: A Randomized, Placebo-Controlled Study , 2002 .

[26]  J. Biederman,et al.  Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders. , 1991, The American journal of psychiatry.

[27]  D. Faries,et al.  Validation of the ADHD Rating Scale as a clirlician administered and scored instrument , 2001 .

[28]  J. Swanson,et al.  ADHD treatment with once-daily OROS methylphenidate: interim 12-month results from a long-term open-label study. , 2003, Journal of the American Academy of Child and Adolescent Psychiatry.

[29]  M. Rapport,et al.  Attention deficit/hyperactivity disorder and methylphenidate. A review of height/weight, cardiovascular, and somatic complaint side effects. , 2002, Clinical psychology review.

[30]  T. Wilens,et al.  Do children and adolescents with ADHD respond differently to atomoxetine? , 2006, Journal of the American Academy of Child and Adolescent Psychiatry.

[31]  P. Zeiner,et al.  Does extended medication with amphetamine or methylphenidate reduce growth in hyperactive children? , 2002, Nordic journal of psychiatry.

[32]  S. Rivkees,et al.  Daily Methylphenidate Use Slows the Growth of Children: A Community Based Study , 2003, Journal of pediatric endocrinology & metabolism : JPEM.