Efficacy and safety of extended-release dexmethylphenidate compared with d,l-methylphenidate and placebo in the treatment of children with attention-deficit/hyperactivity disorder: a 12-hour laboratory classroom study

J Child Adolesc Psychopharmacol. 2008 Jun;18(3):248-56. doi: 10.1089/cap.2007.0015.


Objective: This study compared the efficacy and safety of extended-release dexmethylphenidate (d-MPH-ER) 20 mg/day and 30 mg/day with extended-release racemic methylphenidate hydrochloride (d,l-MPH-ER) 36 mg/day and 54 mg/day, and placebo in children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting.

Methods: This multicenter, double-blind, crossover study included children (N = 84) 6-12 years of age, stabilized on total daily doses of 40 mg to 60 mg d,l-MPH or 20 mg/day or 30 mg/day d-MPH who were randomized to different treatment sequences. Primary efficacy was measured by the change from pre-dose in Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale-Combined scores at 2 hours post-dose (d-MPH-ER 20 mg/day versus d,l-MPH- ER 36 mg/day). Adverse events were monitored throughout the study period.

Results: Mean change in SKAMP-Combined score at 2 hours post-dose was significantly larger for d-MPH-ER 20 mg/day versus d,l-MPH-ER 36 mg/day (p < 0.001). Both doses of d-MPH-ER had a more rapid onset and greater morning effect relative to d,l-MPH-ER while d,l-MPH-ER had a greater effect at the end of the 12-hour day. All active treatments provided a significant benefit over placebo at most time points to 12 hours post-dosing. Both treatments were well tolerated.

Conclusions: d-MPH-ER and d,l-MPH-ER improved ADHD symptoms and were well tolerated. While d-MPH-ER had a faster onset of action, d,l-MPH-ER retained greater effect at the end of the 12- hour classroom day.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Chemistry, Pharmaceutical
  • Child
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Dexmethylphenidate Hydrochloride*
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Headache / chemically induced
  • Headache / psychology
  • Humans
  • Male
  • Methylphenidate / administration & dosage*
  • Methylphenidate / adverse effects*
  • Methylphenidate / chemistry
  • Placebos
  • Schools*
  • Social Environment
  • Time Factors
  • Treatment Outcome


  • Delayed-Action Preparations
  • Placebos
  • Dexmethylphenidate Hydrochloride
  • Methylphenidate