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.