Treatment of children with attention-deficit/hyperactivity disorder: results of a randomized, multicenter, double-blind, crossover study of extended-release dexmethylphenidate and D,L-methylphenidate and placebo in a laboratory classroom setting

Psychopharmacol Bull. 2008;41(1):19-33.


The purpose of this study was to compare the efficacy and safety of extended-release dexmethylphenidate (d-MPH-ER) to that of d,l-MPH-ER and placebo in children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. This multicenter, double-blind, crossover study randomized 82 children, 6 to 12 years of age, stabilized on a total daily dose to the nearest equivalent of 40 to 60 mg of d,l-MPH or 20 or 30 mg/day of d-MPH. Patients participated in a screening day and practice day, and were randomized to 1 of 10 sequences of all five treatments in five separate periods. Treatments included d-MPH-ER (20 mg/day), d-MPH-ER (30 mg/day), d,l-MPH-ER (36 mg/day), d,l-MPH-ER (54 mg/day), and placebo. Primary efficacy was measured by the change from predose on the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale-Combined scores at 2-h postdose during the 12-h laboratory assessment (d-MPH-ER 20 mg/day vs. d,l-MPH-ER 36 mg/day). Adverse events were monitored throughout the study period. d-MPH-ER (20 mg/day) was significantly more effective than d,l-MPH-ER (36 mg/day) in the primary efficacy variable, change from predose to 2-h postdose in SKAMP-combined score. In general, d-MPH-ER had an earlier onset of action than d,l-MPH-ER, while d,l-MPH-ER had a stronger effect at 12-h postdose. No serious adverse events were reported. Treatment with either agent was associated with significant improvements in ADHD symptoms. d-MPH-ER and d,l-MPH-ER can be differentiated on what part of the day each is more effective.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Area Under Curve
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Central Nervous System Stimulants / administration & dosage*
  • Central Nervous System Stimulants / adverse effects
  • Child
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Dexmethylphenidate Hydrochloride*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Methylphenidate / administration & dosage*
  • Methylphenidate / adverse effects
  • Placebos


  • Central Nervous System Stimulants
  • Delayed-Action Preparations
  • Placebos
  • Dexmethylphenidate Hydrochloride
  • Methylphenidate