Low Dopamine Transporter Occupancy by Methylphenidate as a Possible Reason for Reduced Treatment Effectiveness in ADHD Patients With Cocaine Dependence

Eur Neuropsychopharmacol. 2013 Dec;23(12):1714-23. doi: 10.1016/j.euroneuro.2013.05.002. Epub 2013 May 31.


Methylphenidate (MPH) occupies brain striatal dopamine transporters (DATs) and is an effective treatment for attention deficit hyperactivity disorder (ADHD). However, patients with ADHD and comorbid cocaine dependence do not benefit significantly from treatment with MPH. To better understand the neurobiology of this phenomenon, we examined DAT availability and the effects of MPH treatment on DAT occupancy in ADHD patients with and without cocaine dependence. ADHD patients without a comorbid substance use disorder (N=16) and ADHD patients with comorbid cocaine dependence (N=8) were imaged at baseline and after two weeks MPH treatment using single photon emission computed tomography (SPECT) with the DAT tracer [(123)I]FP-CIT. Changes in ADHD symptoms were measured with the ADHD symptom rating scale (ASRS). At baseline, we observed lower striatal DAT availability in ADHD patients with cocaine dependence. Following fixed MPH treatment, MPH occupied significantly less striatal DATs in cocaine-dependent than in non-cocaine dependent ADHD patients. There were no significant correlations between baseline DAT availability or DAT occupancy by MPH and ADHD symptom improvement. However, we did find significant correlations between DAT occupancy by MPH and decreases in impulsivity scores and years of cocaine use. These preliminary findings suggest that low DAT occupancy is not the reason why ADHD patients with cocaine dependence do not benefit from MPH treatment. It also suggests that higher dosages of MPH in these patients are probably not the solution and that medications directed at other pharmacological targets should be considered in these comorbid ADHD patients. This trial is registered at the Dutch Trial Register, www.trialregister.nl, under Trial ID number NTR3127.

Keywords: Attention deficit hyperactivity disorder; Cocaine addiction; Dopamine transporter; Methylphenidate; SPECT; Substance use disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Attention Deficit Disorder with Hyperactivity / complications*
  • Attention Deficit Disorder with Hyperactivity / diagnostic imaging
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / pathology
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Central Nervous System Stimulants / therapeutic use*
  • Cocaine-Related Disorders / blood
  • Cocaine-Related Disorders / complications*
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Female
  • Humans
  • Imaging, Three-Dimensional
  • Male
  • Methylphenidate / blood
  • Methylphenidate / therapeutic use*
  • Middle Aged
  • Protein Binding / drug effects
  • Psychiatric Status Rating Scales
  • Tomography, Emission-Computed, Single-Photon
  • Tropanes
  • Young Adult


  • Central Nervous System Stimulants
  • Dopamine Plasma Membrane Transport Proteins
  • Tropanes
  • 2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane
  • Methylphenidate