title: A pilot evaluation of the safety, tolerability, pharmacokinetics, and effectiveness of memantine in pediatric patients with attention-deficit/hyperactivity disorder combined type.
abstract: BACKGROUND
  Disturbances in N-methyl-D-aspartate (NMDA) receptor activity may play a role in attention-deficit/hyperactivity disorder (ADHD).
  
  
  OBJECTIVE
  This study is a preliminary evaluation of the safety, pharmacokinetics, and effectiveness of the NMDA receptor antagonist memantine in pediatric ADHD.
  
  
  METHODS
  An open-label, dose-finding, 8-week, trial in outpatients 6-12 years old with ADHD combined type. Memantine oral solution (2 mg/mL) was titrated to 10 mg/day (n = 8) or 20 mg/day (n = 8). Safety data and blood samples for pharmacokinetic analyses were collected. The ADHD Rating Scale-IV (ADHD-IV) and Clinical Global Impression of Severity (CGI-S) scale measured the effectiveness of memantine.
  
  
  RESULTS
  There were no discontinuations due to adverse events (AEs), serious AEs, deaths, or suicides. Most AEs were mild and occurred during the first week of treatment. The 20 mg/day memantine dose was associated with a higher rate of completion and larger mean improvement on the ADHD-IV and CGI-S than 10 mg/day memantine. Pharmacokinetic analyses suggest response to memantine may be dose-dependent beyond an initial threshold concentration.
  
  
  CONCLUSIONS
  This pilot study suggests that a memantine dose of 20 mg/day may be a safe and possibly effective treatment for pediatric ADHD. Further investigations of memantine in ADHD appear to be warranted.
authors.affiliation: Department of Psychiatry, Case Western Reserve University and Division of Child & Adolescent Psychiatry, University Hospitals of Cleveland, Cleveland, Ohio 44106-5080, USA. Robert.Findling@uhhs.com
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
authors.forename: Nora K
authors.initials: NK
authors.lastname: McNamara
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Stansbrey
authors.forename: Rebecca
authors.initials: R
authors.lastname: Maxhimer
authors.forename: Antonia
authors.initials: A
authors.lastname: Periclou
authors.forename: Allison
authors.initials: A
authors.lastname: Mann
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Graham
mesh_terms: D000284:Administration, Oral; D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood / Q000188:drug therapy*; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008559:Memantine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D010865:Pilot Projects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D008559:Memantine