ADHD Attention Deficit and Hyperactivity Disorders

, Volume 6, Issue 4, pp 291–302

Findings from the observational COMPLY study in children and adolescents with ADHD: core symptoms, ADHD-related difficulties, and patients’ emotional expression during psychostimulant or nonstimulant ADHD treatment

  • Ralf W. Dittmann
  • Tobias Banaschewski
  • Alexander Schacht
  • Peter M. Wehmeier
Original Article


The aim of this study was to explore the course of attention-deficit/hyperactivity disorder (ADHD) core symptoms, ADHD-related difficulties, and emotional expression during ADHD pharmacotherapy and associations between them. This prospective, observational study examines pediatric patients with ADHD who newly initiated stimulant, atomoxetine or a combination of both treatments. Data were collected at baseline; weeks 1, 2, and 4; and months 3, 6, 9, and 12. Physicians rated ADHD core symptoms using the ADHD Rating Scale (ADHD-RS); patients, parents, and physicians rated ADHD-related difficulties using the Global Impression of Perceived Difficulties (GIPD) Scale; and patients and parents rated emotional expression using the Expression of Emotion Scale for Children (EESC). Results were analyzed using mixed model repeated measures. Associations are presented by Spearman’s correlations. Overall, 504 patients, mean age 9.6 years, 72.6 % males, were analyzed. Fifty percent of patients started atomoxetine, 49.0 % stimulant and 1 % a combination of both. ADHD-RS, GIPD, and EESC scores decreased significantly in both monotherapy groups. Correlations between ADHD-RS and parent- or physician-rated GIPD scores were at-best moderate and increased over time but remained low to moderate for patient-rated GIPD [patient, r = 0.43 (95 % CI 0.34, 0.51); parent, r = 0.58 (0.50, 0.64); physician, r = 0.55 (0.48, 0.62)]. Correlations between ADHD-RS and patient- or parent-rated EESC scores were low at baseline (r < 0.2) and increased over time mostly for parent ratings [patient, r = 0.35 (0.26, 0.44); parent, r = 0.41 (0.32, 0.50)]. These data support the effectiveness of ADHD pharmacotherapy. The at-best moderate correlations between ADHD core symptoms and ADHD-related difficulties or emotional expression assessed by different raters indicate potentially important patient outcomes beyond core symptoms.


Atomoxetine Stimulants Parent/patient perspectives Emotional expression ADHD-related difficulties 


  1. Abikoff HB, Vitiello B, Riddle MA et al (2007) Methylphenidate effects on functional outcomes in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS). J Child Adolesc Psychopharmacol 17:581–592PubMedCrossRefGoogle Scholar
  2. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4 (text revision) (DSM-IV-TR) edn. American Psychiatric Publishing, Washington, DCGoogle Scholar
  3. Banaschewski T, Coghill D, Santosh P et al (2006) Long-acting medications for the hyperkinetic disorders. A systematic review and European treatment guideline. Eur Child Adolesc Psychiatry 15:476–495PubMedCrossRefGoogle Scholar
  4. Banaschewski T, Jennen-Steinmetz C, Brandeis D et al (2012) Neuropsychological correlates of emotional lability in children with ADHD. J Child Psychol Psychiatry 53:1139–1148. doi:10.1111/j.1469-7610.2012.02596.x PubMedCentralPubMedCrossRefGoogle Scholar
  5. Barkley RA (2002) Major life activity and health outcomes associated with attention-deficit/hyperactivity disorder. J Clin Psychiatry 63(Suppl 12):10–15PubMedGoogle Scholar
  6. Barkley RA, Fischer M, Smallish L, Fletcher K (2006) Young adult outcome of hyperactive children: adaptive functioning in major life activities. J Am Acad Child Adolesc Psychiatry 45:192–202PubMedCrossRefGoogle Scholar
  7. Biederman J, Faraone SV, Spencer T et al (1993) Patterns of psychiatric comorbidity, cognition, and psychosocial functioning in adults with attention deficit hyperactivity disorder. Am J Psychiatry 150:1792–1798PubMedGoogle Scholar
  8. Canadian Attention Deficit Hyperactivity Disorder Resource Alliance (2000) Weiss Functional Impairment Rating Scale—Parent Report (WFIRS-P). Accessed Jan 14 2014
  9. Cox DJ, Merkel RL, Kovatchev B, Seward R (2000) Effect of stimulant medication on driving performance of young adults with attention-deficit hyperactivity disorder: a preliminary double-blind placebo controlled trial. J Nerv Ment Dis 188:230–234PubMedCrossRefGoogle Scholar
  10. d’Agostino RB (1998) Tutorial in biostatistics: propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med 17:2265–2281PubMedCrossRefGoogle Scholar
  11. Dittmann RW, Wehmeier PM, Schacht A et al (2009) Atomoxetine treatment and ADHD-related difficulties as assessed by adolescent patients, their parents and physicians. Child Adolesc Psychiatry Ment Health 3:21. doi:10.1186/1753-2000-3-21 PubMedCentralPubMedCrossRefGoogle Scholar
  12. DuPaul GJ, Power TJ, Anastopoulos AD, Reid R (1998) ADHD Rating Scale-IV: checklists, norms, and clinical interpretations. Guilford Press, New YorkGoogle Scholar
  13. Escobar R, Soutullo CA, Hervas A, Gastaminza X, Polavieja P, Gilaberte I (2005) Worse quality of life for children with newly diagnosed attention-deficit/hyperactivity disorder, compared with asthmatic and healthy children. Pediatrics 116:e364–e369PubMedCrossRefGoogle Scholar
  14. Faries DE, Yalcin I, Harder D, Heiligenstein JH (2001) Validation of the ADHD Rating Scale as a clinician administered and scored instrument. J Atten Disord 5:107–115CrossRefGoogle Scholar
  15. Flapper BC, Schoemaker MM (2008) Effects of methylphenidate on quality of life in children with both developmental coordination disorder and ADHD. Dev Med Child Neurol 50:294–299. doi:10.1111/j.1469-8749.2008.02039.x PubMedCrossRefGoogle Scholar
  16. German Federal Institute for Drugs and Medical Devices (2009) Announcement on the authorisation and registration of medicinal products: recommendations for design and conduct of observational post-authorisation safety studies (Federal Gazette No. 229, p. 16884). Accessed Jan 14 2014
  17. Guy W (1976) ECDEU assessment manual for psychopharmacology: Publication ADM 76–338. US Department of Health, Education and Welfare, WashingtonGoogle Scholar
  18. Hodgkins P, Dittmann RW, Sorooshian S, Banaschewski T (2013) Individual treatment response in attention-deficit/hyperactivity disorder: broadening perspectives and improving assessments. Expert Rev Neurother 13:425–433. doi:10.1586/ern.13.31 PubMedCrossRefGoogle Scholar
  19. Kelsey DK, Sumner CR, Casat CD et al (2004) 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. Pediatrics 114:e1–e8PubMedCrossRefGoogle Scholar
  20. Kratochvil CJ, Faries D, Vaughan B et al (2007) Emotional expression during attention-deficit/hyperactivity disorders treatment: initial assessment of treatment effects. J Child Adolesc Psychopharmacol 17:51–62PubMedCrossRefGoogle Scholar
  21. Landgraf JM, Abetz L, Ware JE (1999) The CHQ: a user’s manual (2nd Printing). HealthAct, BostonGoogle Scholar
  22. Matza LS, Stoeckl MN, Shorr JM, Johnston JA (2006) Impact of atomoxetine on health-related quality of life and functional status in patients with ADHD. Expert Rev Pharmacoecon Outcomes Res 6:379–390. doi:10.1586/14737167.6.4.379 PubMedCrossRefGoogle Scholar
  23. Michelson D, Faries D, Wernicke J et al (2001) Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study. Pediatrics 108:E83PubMedCrossRefGoogle Scholar
  24. Michelson D, Allen AJ, Busner J et al (2002) Once-daily atomoxetine treatment for children and adolescents with attention-deficit hyperactivity disorder: a randomized, placebo-controlled study. Am J Psychiatry 159:1896–1901PubMedCrossRefGoogle Scholar
  25. MTA Cooperative Group (1999) 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. Arch Gen Psychiatry 56:1073–1086CrossRefGoogle Scholar
  26. National Institute for Clinical Excellence (2006) Guidance on the use of methylphenidate (Ritalin, Equasym) for attention-deficit/hyperactivity disorder (ADHD) in childhood (2000) Technology appraisal, Guidance No. 13. Accessed Jan 14 2014
  27. National Institutes of Mental Health (1985) Clinical global impressions. Psychopharmacol Bull 21:839–943Google Scholar
  28. Newcorn JH, Halperin JM, Jensen PS et al (2001) Symptom profiles in children with ADHD: effects of comorbidity and gender. J Am Acad Child Adolesc Psychiatry 40:137–146PubMedCrossRefGoogle Scholar
  29. Perwien AR, Faries DE, Kratochvil CJ, Sumner CR, Kelsey DK, Allen AJ (2004) Improvement in health-related quality of life in children with ADHD: an analysis of placebo controlled studies of atomoxetine. J Dev Behav Pediatr 25:264–271PubMedCrossRefGoogle Scholar
  30. Perwien AR, Kratochvil CJ, Faries DE, Vaughan BS, Spencer T, Brown RT (2006) Atomoxetine treatment in children and adolescents with attention-deficit hyperactivity disorder: what are the long-term health-related quality-of-life outcomes? J Child Adolesc Psychopharmacol 16:713–724PubMedCrossRefGoogle Scholar
  31. Perwien AR, Kratochvil CJ, Faries D et al (2008) Emotional expression in children treated with ADHD medication: development of a new measure. J Atten Disord 11:568–579. doi:10.1177/1087054707306117 PubMedCrossRefGoogle Scholar
  32. Prasad S, Harpin V, Poole L et al (2007) A multi-centre, randomised, open-label study of atomoxetine compared with standard current therapy in UK children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Curr Med Res Opin 23:379–394PubMedCrossRefGoogle Scholar
  33. Riley AW, Robertson J, Forrest CB, Green B, Rebok G, Starfield B (2001) Manual for the child health and illness profile—child edition (CHIP-CE). The Johns Hopkins University, BaltimoreGoogle Scholar
  34. Schacht A, Bürger A, Wehmeier PM, Huss M (2012) Evaluation of patient- and parent-rated emotional expression using the Expression and Emotion Scale for Children (EESC) in an observational study of ADHD in children and adolescents. Open Psychiatr J 6:1–12CrossRefGoogle Scholar
  35. Spencer T, Biederman J, Heiligenstein J et al (2001) An open-label, dose-ranging study of atomoxetine in children with attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol 11:251–265PubMedCrossRefGoogle Scholar
  36. Spencer T, Heiligenstein JH, Biederman J et al (2002) Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder. J Clin Psychiatry 63:1140–1147PubMedCrossRefGoogle Scholar
  37. Wehmeier PM, Dittmann RW, Schacht A et al (2007) Effectiveness of atomoxetine and quality of life in children with attention-deficit/hyperactivity disorder as perceived by patients, parents, and physicians in an open-label study. J Child Adolesc Psychopharmacol 17:813–830. doi:10.1089/cap.2007.0025 PubMedCrossRefGoogle Scholar
  38. Wehmeier PM, Schacht A, Dittmann RW, Döpfner M (2008) Global impression of perceived difficulties in children and adolescents with attention-deficit/hyperactivity disorder: reliability and validity of a new instrument assessing perceived difficulties from a patient, parent and physician perspective over the day. Child Adolesc Psychiatry Ment Health 2:10. doi:10.1186/1753-2000-2-10 PubMedCentralPubMedCrossRefGoogle Scholar
  39. Wehmeier PM, Schacht A, Dittmann RW, Banaschewski T (2010) Reasons for physicians’ choice of medication in medication-naïve patients with ADHD: baseline data from the COMPLY observational study. Curr Drug Ther 5:139–150CrossRefGoogle Scholar
  40. Weiss MD, Gadow K, Wasdell MB (2006) Effectiveness outcomes in attention-deficit/hyperactivity disorder. J Clin Psychiatry 67(Suppl 8):38–45PubMedGoogle Scholar
  41. World Health Organization (2004) Multiaxial classification of child and adolescent psychiatric disorders: the ICD-10 classification of mental and behavioural disorders in children and adolescents. Cambridge University Press, CambridgeGoogle Scholar
  42. Yang P, Hsu HY, Chiou SS, Chao MC (2007) Health-related quality of life in methylphenidate-treated children with attention-deficit-hyperactivity disorder: results from a Taiwanese sample. Aust N Z J Psychiatry 41:998–1004PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  • Ralf W. Dittmann
    • 1
  • Tobias Banaschewski
    • 1
  • Alexander Schacht
    • 2
  • Peter M. Wehmeier
    • 1
    • 3
  1. 1.Department for Child and Adolescent Psychiatry, Central Institute of Mental Health, Medical Faculty MannheimUniversity of HeidelbergMannheimGermany
  2. 2.Medical DepartmentLilly Deutschland GmbHBad HomburgGermany
  3. 3.Vitos Hospital for Psychiatry and PsychotherapyWeilmuensterGermany

Personalised recommendations