Imaging Stimulant and Non Stimulant Treatments for ADHD: A Network Based Approach
Condition: Attention Deficit Hyperactivity Disorder; ADHD
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Intervention: fMRI scans; Atomoxetine arm; Methylphenidate arm
Intervention description: 2 fMRI scans 6-8 weeks apart; Flexible dose titration with atomoxetine prescribed at weekly visits for 6-8 weeks; Flexible dose titration with methylphenidate for 6-8 weeks, with optional post study stabilization visits.
Intervention MeSH terms: Methylphenidate; Atomoxetine Hydrochloride
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 127.0
Sex: All
Minimum age: 7 Years
Maximum age: 17 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Attention Deficit Hyperactivity Disorder; Stimulant; Non-stimulant; Drug; Methylphenidate; Atomoxetine; Strattera; Concerta; MACRO; Medication; Treatment; Youth; Adolescent; Functional Magnetic Resonance Imaging; Brain scan; Imaging; Response inhibition; Inattentive; Hyperactive; Combined; Medication Treatment; Brain Imaging

Summary:

      The growing number of medications used to treat attention-deficit/hyperactivity disorder
      (ADHD) raises important questions about whether different medications have similar or
      different therapeutic mechanisms of action. We have recently shown that the stimulant
      methylphenidate (MPH) and the non-stimulant atomoxetine (ATX) produce clinical improvement
      via a common mechanism in motor cortex, and distinct actions in frontostriatal and midline
      cingulate-precuneus regions. These exciting findings offer a window into the common and
      unique neurophysiological mechanisms of response to stimulant and non-stimulant treatments.
      However, the interpretation and clinical utility of these results would be greatly enhanced
      by in-depth investigation of the impact of the two treatments on relevant neural networks,
      and analyses which evaluate whether improvement is achieved via normalization or other
      adaptive changes in brain function.
    

Eligibility criteria:

        Inclusion Criteria:

        General inclusion criteria for subjects with ADHD and healthy controls are:

          -  aged 7-17 years;

          -  Wechsler Intelligence Scale for Children (WISC) scores ≥ 75;

          -  informed consent and assent to study participation.

        Specific inclusion criteria for youth with ADHD are:

          -  diagnosis of ADHD, any subtype, determined by Kiddie Schedule for Affective Disorders
             and Schizophrenia for School-Aged Children-Present and Lifetime Versions (K-SADS-PL);

          -  ADHD Rating Scale-IV-Parent Version: Investigator Administered (ADHD-RSIV) total score
             ≥ 1.5 SD above age and gender means for subtype

          -  Clinical Global Impressions-ADHD-Severity (CGI-S) score > 4;

          -  ADHD must be the primary diagnosis and focus of treatment, and the treatments offered
             in the study must not be contraindicated for the comorbid disorder.

        Exclusion Criteria:

        General exclusion criteria are:

          -  history of head injury with loss of consciousness or any CNS disease that is likely to
             affect brain function;

          -  diagnosis of autism or pervasive developmental, psychotic, major mood, and Tourette's
             disorder;

          -  alcohol or drug abuse in the past 3 months or a positive urinary toxic screen on
             initial evaluation;

          -  use of psychotropic medication within 2 weeks of the study (8 weeks for fluoxetine);

          -  pre-existing medical or psychological condition which precludes being in the scanner
             (e.g., claustrophobia, morbid obesity);

          -  metal in the body that precludes scanning (e.g., braces, metal plate);

          -  positive urine pregnancy test.

        Specific exclusion criteria for the treatment trial include:

          -  previous unsuccessful trial of MPH or ATX that was adequately dosed (≥ 1 mg/kg for MPH
             or 1.0 mg/kg for ATX) and of adequate duration (≥ 4 weeks);

          -  abnormal findings on physical exam, or vital signs

          -  pulse and blood pressure > 95% of age and gender mean;

          -  inability to swallow capsules;

          -  weight is < 20 kg or > 85 kg.

        Specific exclusion criteria for control youth include:

          -  no past history or current diagnosis of any psychiatric disorder, determined by the
             K-SADS-PL interview;

          -  ADHD-RS-IV and CBCL scores for each symptom domain ≤ 1 SD of age and gender means.