Examining Tolerance to CNS Stimulants in ADHD
Condition: Attention-deficit/Hyperactivity Disorder
MeSH terms: Attention Deficit Disorder with Hyperactivity
Study type: Interventional
Phase: Phase 4

Summary: 
      Although stimulant medication is a well-established treatment for ADHD, it is often necessary
      for doctors to increase the dose over time to maintain the benefits of the medication. While
      medication can be very effective for improving symptoms of ADHD during the first year of use,
      it has not been found to significantly improve the long term course of children with ADHD.
      For example, in large research studies, groups of children who take medication for ten years
      do not have consistently better academic grades than groups of children who never used
      medication (individual results will vary from child to child).

      In order to help children with ADHD achieve the best possible outcomes, it is important for
      doctors to study why this happens. One possible reason is development of tolerance to the
      medication. Tolerance means that a drug's effects decrease when it is taken consistently over
      time, so that an increased dose is needed to continue showing effects. Some doctors believe
      that children who take stimulant medication for ADHD develop tolerance to it which would
      explain why benefits may not persist over time, but no research studies have been done to
      measure whether this occurs. This study aims to see if children show a tolerance effect to
      stimulant medication and whether that tolerance can be prevented by taking short breaks from
      the medication called medication holidays.
    

Detailed description: 
      This is an innovative evaluation of tolerance using an objective measure in an analog
      classroom. Each subject will complete the a 10-minute math test twice a day for three weeks
      on optimal dose or placebo, and then be crossed over to the other condition. Within-subject
      drug/placebo differences will be compared over the three weeks of exposure to assess
      tolerance in the analog setting.

      When school commences, 50% of the sample will be randomized to 7-day-a-week (continuous)
      dosing and 50% to 5-day-a- week (weekend holidays) dosing to examine the efficacy of
      prescribed weekend drug holidays for combatting need for dose escalations (tolerance) during
      the school year.

      Participants will be assessed monthly to detect deteriorating functioning. Using a
      standardized protocol, study physicians will increase dose for subjects in either arm who
      meet defined impairment thresholds. The difference between the two dosing conditions will
      inform regarding how best to deal with tolerance in clinical application.
    

Intervention name(s): Methylphenidate
Intervention type(s): Drug
Intervention description(s): Children will receive a double-blind assessment to determine their optimal starting dose of Concerta. Doses will be adjusted over the course of the school year and inceased if tolerance to the medication is detected.
Other intervention name(s): Concerta
Intervention MeSH terms: Methylphenidate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Tolerance to stimulant medication