Effects of methylphenidate, desipramine, and L-dopa on attention and inhibition in children with Attention Deficit Hyperactivity Disorder

Behav Brain Res. 2003 Oct 17;145(1-2):7-15. doi: 10.1016/s0166-4328(03)00097-4.


The objective of this study was to investigate the effects of methylphenidate (MPH) on attention and inhibition in children with Attention Deficit Hyperactivity Disorder (ADHD) and to establish what the relative contributions of the noradrenergic and dopaminergic systems to this effect were. In addition to MPH, two other drugs were administered in order to affect both transmitter systems more selectively, L-dopa (dopamine (DA) agonist) and desipramine (DMI) (noradrenaline (NA) re-uptake inhibitor). Sixteen children with ADHD performed a stop-task, a laboratory task that measures the ability to inhibit an ongoing action, in a double-blind randomized within-subjects design. Each child received an acute clinical dose of MPH, DMI, L-dopa, and placebo; measures of performance and plasma were determined. The results indicated that inhibition performance was improved under DMI but not under MPH or L-dopa. The response-time to the stop-signal was marginally shortened after intake of DMI. MPH decreased omission and choice-errors and caused faster reaction times to the trials without the stop-tone. No effects of L-dopa whatsoever were noted. Prolactin levels were increased and 5-HIAA levels were lowered under DMI relative to placebo. It is suggested that the effects of MPH on attention are due to a combination of noradrenergic and dopaminergic mechanisms. The improved inhibition under DMI could be serotonergically mediated.

Publication types

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

MeSH terms

  • Attention / drug effects*
  • Attention Deficit Disorder with Hyperactivity / blood
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / physiopathology
  • Child
  • Choice Behavior / drug effects
  • Desipramine / analogs & derivatives
  • Desipramine / blood
  • Desipramine / therapeutic use*
  • Dopamine Agents / therapeutic use*
  • Double-Blind Method
  • Enzyme Inhibitors / blood
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Hydroxyindoleacetic Acid / blood
  • Inhibition, Psychological*
  • Levodopa / therapeutic use*
  • Male
  • Methylphenidate / therapeutic use*
  • Prolactin / blood
  • Reaction Time / drug effects


  • Dopamine Agents
  • Enzyme Inhibitors
  • Methylphenidate
  • Levodopa
  • Hydroxyindoleacetic Acid
  • Prolactin
  • Desipramine