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Comparison of symptomatic versus functional changes in children and adolescents with ADHD during randomized, double-blind treatment with psychostimulants, atomoxetine, or placebo


  • Conflict of interest statement: This work was sponsored by Eli Lilly and Company. Dr. Buitelaar has been a consultant for Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Lilly, Organon, and UCB, and has been a speaker for Janssen, Lilly, and UCB. Dr. Wilens has received research grants from Cephalon, GlaxoSmithKline, Janssen, Lilly, NeuroSearch, New River, McNeil, Novartis, and Shire. He has been a consultant for Abbott, Cephalon, Lilly, NeuroSearch, Novartis, McNeil, Sanofi-Sythelabo, and Shire and has been a speaker for Abbott, Celltech, Cephalon, GlaxoSmithKline, Janssen, Lilly, McNeil, NeuroSearch, Novartis, Saegis, and Shire. Ms. Zhang and Dr. Feldman are employees of Eli Lilly and Company. Mr. Ning is a former employee of Eli Lilly and Company.

Jan K. Buitelaar, Department of Psychiatry, Radboud University Nijmegen Medical Centre and Karakter University Centre for Child and Adolescent Psychiatry, P.O. Box 9101, 6500HB Nijmegen, The Netherlands; Tel: (+31) 24/361-3490; Fax: (+31) 24/354-6461; Email:


Background:  This meta-analysis was designed to determine the relationship between reduction of attention-deficit/hyperactivity disorder (ADHD) symptoms and improvement in functioning by examining short-term changes in functional and symptomatic scores in children and adolescents with ADHD.

Methods:  Search of atomoxetine’s clinical trial database identified four studies involving a symptomatic measure, the ADHD Rating Scale-IV-Parent Version:Investigator-administered and -scored (ADHDRS-IV-Parent:Inv), and a functional measure, the Life Participation Scale for ADHD (LPS).

Results:  Correlation analysis revealed a moderate-to-strong association between changes in the LPS total versus ADHDRS-IV-Parent:Inv total (r: −.68). The LPS Self-control subscale showed higher correlations than the Happy/Social subscale with the symptomatic measures. Regression analysis also showed high sensitivity for functional measures to changes in symptom severity. Stratified analysis of mean changes in ADHDRS-IV-Parent:Inv scores corresponding to standardized changes in LPS functional scores indicated that a threshold reduction of 16–18 points on the ADHDRS-IV-Parent:Inv total score was needed for functional improvements to become evident.

Conclusions:  Subjects’ symptomatic improvements appear to be reflected in improvements in their social and behavioral function as measured by the LPS. These initial findings warrant verification by replication with other outcome measures.