title: An observational study of response heterogeneity in children with attention deficit hyperactivity disorder following treatment switch to modified-release methylphenidate.
abstract: BACKGROUND
  Methylphenidate (MPH) has been shown to be effective in the treatment of attention deficit hyperactivity disorder (ADHD) in children. The overall population of children and adolescents with ADHD may comprise distinct clusters of patients that differ in response to MPH. The aim of this analysis was to look for subgroups with different treatment trajectories and to identify their distinctive features.
  
  
  METHODS
  OBSEER was a prospective, observational study examining the effectiveness and safety of once-daily modified-release MPH over 3 months in patients (aged 6-17 years) with ADHD under routine care. Assessments were carried out at baseline (Visit 1), after 1-3 weeks (Visit 2) and 6-12 weeks (Visit 3) after first use of once-daily modified-release MPH. Change in ADHD symptoms, as rated by parents and teachers, was examined post hoc in patients of the intent-to-treat-population (N = 822), using growth-mixture modelling to detect response trajectory groups after switching medication. Age, MPH dose at Visit 1 before medication switch, prescribed once-daily modified-release MPH dose at Visits 1 and 2, conduct problems and emotional symptoms were considered predictors of response subgroups.
  
  
  RESULTS
  Assessing formal statistical criteria and usefulness of the models, a 4-class solution best fitted the data: after switching medication two response groups with severe symptoms at study start and subsequent substantial treatment effects, and two showing no or comparatively little treatment effect, one of which had severe and the other less severe symptoms at study start. Patient age, conduct problems and MPH dose at Visit 1 were predictors of inclusion in subgroups.
  
  
  CONCLUSIONS
  Older children and children with few conduct problems were more likely to be members of a patient cluster with fewer symptoms at study start. Children with a low MPH dose before medication switch had a higher chance of being in the patient cluster with a strong treatment response after switching medication. The current analyses should assist in identifying children likely to achieve a favourable treatment course with MPH and, additionally, those who are in need of alternative treatment options.
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy, University of Cologne, Robert-Koch-Str, 10, 50931 Cologne, Germany. manfred.doepfner@uk-koeln.de.
authors.forename: Christopher
authors.initials: C
authors.lastname: Hautmann
authors.forename: Aribert
authors.initials: A
authors.lastname: Rothenberger
authors.forename: Manfred
authors.initials: M
authors.lastname: Döpfner
mesh_terms: D000293:Adolescent; D000367:Age Factors; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate