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
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      The specific aims of this project are to use functional magnetic resonance imaging (fMRI) to
      determine the significance of activation changes over treatment related to clinical
      improvement, and the impact of treatment on neural connectivity within and between the
      anti-correlated frontostriatal 'task-positive' circuit and cingulate-precuneus
      'task-negative' network. Our central hypotheses are that clinical improvement is associated
      with: (i) normalization of reduced connectivity of regions within the 'task-positive'
      network, with resultant increased inhibition of motor cortex, and (ii) normalization of low
      task-related connectivity in regions within the task-negative network for MPH and the
      'task-positive' network for ATX.

      This research proposes to test a model which posits a neurophysiological basis of mechanisms
      of response to stimulant and non-stimulant medications, and fits with our long term
      objectives of being able to match treatments to individual patients. Testing this model
      requires large samples of youth scanned using fMRI before and after treatment, and matched
      healthy controls also scanned twice. We will use an innovative network-based approach to
      study the effects of treatment, building on results from our current fMRI treatment study,
      and incorporating new theoretical approaches to understanding ADHD and its treatment.
    

Intervention name(s): fMRI scans; Atomoxetine arm; Methylphenidate arm
Intervention type(s): Other; Drug; Drug
Intervention description(s): 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.
Other intervention name(s): Strattera; ATX; Concerta; MPH
Intervention MeSH terms: Methylphenidate; Atomoxetine Hydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
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