The neuropsychological effects of chronic methylphenidate on drug-naive boys with attention-deficit/hyperactivity disorder

Biol Psychiatry. 2007 Nov 1;62(9):954-62. doi: 10.1016/j.biopsych.2006.12.030. Epub 2007 Jun 1.


Background: The reported neuropsychological effects of methylphenidate (MPH) in attention-deficit/hyperactivity disorder (ADHD) are inconsistent. The assumed relationships between these neuropsychological effects and clinical efficacy have not been substantiated. We therefore investigated the effects of chronic MPH administration on neuropsychological functioning.

Methods: We conducted a 12-week, placebo-controlled, double-blinded, randomized, crossover trial (MPH .3 and .6 mg/kg/dose and placebo). Participants were 75 boys aged 7-15 years with ADHD. Neuropsychological performance was assessed with tests taken from the Cambridge Neuropsychological Test Automated Battery (CANTAB) battery and a GoNoGo task.

Results: Chronic MPH improved performance (p < .001) on aspects of the GoNoGo task (p < .02) and on three CANTAB tasks which together contributed to a "recognition memory" component identified through principal components analysis (delayed matching to sample [DMtS], pattern and spatial recognition). There were no effects on other, high or low "executive demand" tasks (p > .05). GoNoGo performance improvements were the only neuropsychopharmacological changes associated with clinical response. Poor performance on the DMtS task was the sole baseline neuropsychological predictor of clinical response.

Conclusions: Chronic MPH predominantly enhanced neuropsychological functioning on "recognition memory" component tasks with modest "executive" demands. Neuropsychological measures offer only modest contributions to the prediction of clinical responses to MPH in ADHD.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Association Learning / drug effects
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / physiopathology*
  • Central Nervous System Stimulants / administration & dosage*
  • Child
  • Choice Behavior / drug effects
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Routes
  • Humans
  • Male
  • Methylphenidate / administration & dosage*
  • Neuropsychological Tests / statistics & numerical data*
  • Predictive Value of Tests
  • Principal Component Analysis
  • Problem Solving / drug effects
  • Reaction Time / drug effects
  • Recognition, Psychology / drug effects
  • Time Factors


  • Central Nervous System Stimulants
  • Methylphenidate