title: A double-blind, placebo-controlled trial of dexmethylphenidate hydrochloride and d,l-threo-methylphenidate hydrochloride in children with attention-deficit/hyperactivity disorder.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of dexmethylphenidate hydrochloride (d-MPH, Focalin) for the treatment of attention-deficit/hyperactivity disorder (ADHD) and to test an a priori hypothesis that d-MPH would have a longer duration of action than d,l-threo-methylphenidate (d,l-MPH).
  
  
  METHODS
  This was a randomized, double-blind study conducted at 12 U.S. centers. One hundred thirty-two subjects received d-MPH (n=44), d,l-MPH (n=46), or placebo (n=42) twice daily for 4 weeks, with titration of the dose based on weekly clinic visits. The primary efficacy variable was change from baseline to last study visit on teacher-completed Swanson, Nolan, and Pelham Rating Scale (Teacher SNAP). Secondary efficacy measures included the change on parent-completed SNAP (Parent SNAP), Clinical Global Impressions Scale-Improvement (CGI-I) score, and Math Test performance. Assessments at home in late afternoon were included to test the hypothesis that d-MPH would have a longer duration of efficacy than d,l-MPH. Safety was assessed through monitoring occurrence and severity of adverse events and discontinuations related to them.
  
  
  RESULTS
  Treatment with either d-MPH (p=.0004) or d,l-MPH (p=.0042) significantly improved Teacher SNAP ratings compared with placebo. The d-MPH group showed significant improvements compared with placebo on the afternoon Parent SNAP ratings (p=.0003) and scores on the Math Test (p=.0236) obtained late in the afternoon at 6:00 p.m. Sixty-seven percent of patients showed improvement on d-MPH and 49% on d,l-MPH based on CGI-I scores. Both d-MPH and d,l-MPH were well tolerated, no patient in the d-MPH group and only two patients each in the d,l-MPH and placebo groups discontinued the study.
  
  
  CONCLUSIONS
  For the treatment of ADHD, an average titrated dose of 18.25 mg/day of d-MPH is as efficacious and safe as an average titrated dose of 32.14 mg/day of d,l-MPH. Both active treatments have large effect sizes. Thus, d-MPH and d,l-MPH appear to provide similar efficacy, and d-MPH may have longer duration of action after twice-daily dosing, but additional studies are needed to determine the statistical and clinical significance of this possibility.
authors.affiliation: Irvine Child Development Center, University of California, Irvine, CA 92612, USA. sbwigal@uci.edu
authors.forename: Sharon
authors.initials: S
authors.lastname: Wigal
authors.forename: James M
authors.initials: JM
authors.lastname: Swanson
authors.forename: David
authors.initials: D
authors.lastname: Feifel
authors.forename: R Bart
authors.initials: RB
authors.lastname: Sangal
authors.forename: Josephine
authors.initials: J
authors.lastname: Elia
authors.forename: Charles D
authors.initials: CD
authors.lastname: Casat
authors.forename: Jerome B
authors.initials: JB
authors.lastname: Zeldis
authors.forename: C Keith
authors.initials: CK
authors.lastname: Conners
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D002648:Child; D064699:Dexmethylphenidate Hydrochloride; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D010919:Placebos; D012720:Severity of Illness Index; D013237:Stereoisomerism; D016896:Treatment Outcome
chemical_list: D000697:Central Nervous System Stimulants; D010919:Placebos; D064699:Dexmethylphenidate Hydrochloride; D008774:Methylphenidate