This study evaluates the effects of receiving and then discontinuing methylphenidate (MPH) in children with ADHD. After receiving MPH for 8 weeks, participants will be randomized to either discontinue MPH (and receive placebo) OR remain on MPH for 4 weeks.
The stimulant methylphenidate (MPH) is the most commonly prescribed psychoactive medication in children. An abundance of studies attest to the efficacy of MPH for attenuating inattentive, hyperactive, and impulsive symptoms in children with ADHD. Despite its efficacy, most children with ADHD who are prescribed MPH have poor continuity of treatment for a variety of reasons, including forgetting to administer the medication and delays obtaining refills. In addition, it is an accepted clinical practice for physicians to omit MPH for periods of time, such as during the summer or on weekends (i.e., drug holidays). Since MPH discontinuation is considered to be benign, many clinicians do not employ any special procedures or inform families of any special precautions in regard to its cessation. However, increasing evidence suggests that the pharmacological effects of MPH cause lasting changes in brain neurochemistry that persist beyond medication discontinuation. Moreover, these neurobiological effects of discontinuation appear to have neurobehavioral consequences. There is a critical need to better understand the breadth and magnitude of the neurobehavioral effects caused by MPH discontinuation as well as to better understand the temporal trajectory of these deleterious effects. Hence, the primary goal of the proposed research is to conduct the first randomized, double-blind, placebo-controlled trial specifically designed to study the negative effects of MPH discontinuation at multiple time points. 180 children diagnosed with ADHD will participate across two recruitment sites. After undergoing a 4-week MPH titration trial and 4-week MPH maintenance phase, participants will be randomized to either discontinue MPH (and receive placebo) OR remain on MPH for 4 weeks. Comprehensive multi-time point, multi-informant (parents, teachers, study staff) and multi-modal (behavior/mood/affect ratings scales, direct behavior observations, standardized testing) assessments will be used to assess a broad range of neurobehavioral outcomes. We will examine the magnitude and time course of effects of MPH discontinuation on behavioral as well as cognitive and academic functioning in children with ADHD. Furthermore, we will examine moderators of the adverse effects of MPH discontinuation on these outcomes to aid in the identification of those who are at increased risk.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
204
OROS-methylphenidate will be taken orally once daily at doses that have been approved for the study age group by the U.S. FDA.
Children's Hospital Medical Center
Cincinnati, Ohio, United States
Seattle Children's Hospital
Seattle, Washington, United States
Parent ADHD Total Symptom Scores
Parent Vanderbilt ADHD Rating Scale Total Symptom Score, minimum=0, maximum=54, higher scores indicate more/worse ADHD symptoms
Time frame: baseline, study weeks 8, 9, 10, 12
Inhibitory Control Reaction Time Variability (SD of the Reaction Time)
Assessed via the Go/No-Go computerized measure of inhibitory control reaction time variability (with standard deviation of the reaction time being the indicator variability variability). Unit of measure is msec. Minimum is 0, Maximum is 500. Higher scores indicate more variability (higher standard deviation) in reaction time, indicating worse outcome (more characteristic of individuals with ADHD and less characteristic of typically developing individuals).
Time frame: baseline, study weeks 8, 9, 10 & 12
Math Computation - Number of Problems Completed Correctly
Math Computation Curriculum-Based Measure - Number of Problems Completed Correctly. Minimum=0, Maximum=600. Higher scores indicate improved/better performance
Time frame: baseline, study weeks 8, 9, 10 & 12
% Time on Task
Participants were videotaped while completing the 20-minute Analogue Math task. Their behavior was coded in 20-second intervals by trained coders who determined if the children were on-task or off-task during each interval. The amount of time coded as on-task was divided by the total amount of time and then multiplied by 100 to generate the % of time on task variable.
Time frame: baseline, study weeks 8, 9, 10, 12
Barkley Sluggish Cognitive Tempo (SCT) Ratings
assessed via parent-completed Barkley Sluggish Cognitive Tempo Scale. Minimum=12, Max=48, higher scores indicate worse outcome.
Time frame: baseline, study weeks 8, 9, 10 &12
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Parent Ratings of Emotional Regulation
assessed via parent-completed Emotion Regulation Checklist (ERC). Outcome assessed is ERC total mean score: minimum value=1, max value=4, higher scores indicate worse outcome
Time frame: baseline, study weeks 8, 9, 10 &12
Spatial Working Memory
Spatial working memory was assessed via the Corsi Computerized Spatial Span Task, which requires the participant to reproduce a sequence of movements by tapping a series of blocks on a computer screen in the same order demonstrated by the examiner. Outcome of interest is total trials correct. Minimum score=0, max score=10. Higher scores indicate better performance.
Time frame: baseline, study weeks 8, 9, 10 &12
Math Reasoning
Math reasoning was assessed by child completion of the AIMSWEB curriculum based measure (CBM) test of Math Concepts and Applications. At baseline (week 1), child's performance was assigned a value of 1.0. The child's performance at weeks 8, 9, 10, and 12 was derived by dividing actual score on the test by the score predicted at that time point after applying the measure's normed "rate of improvement (ROI)" metric to the baseline score. For example, a score of 1.5 at week 8 would indicate that the child's actual score at week 8 was 50% higher than the predicted score at week 8 (which was derived by applying the normed ROI metric to the baseline score). Scores at weeks 8, 9, 10, 12 that are \>1.0 indicate greater improvement than expected (so better outcome), while scores at weeks 8, 9, 10, 12 that are \<1.0 indicate less improvement than expected (so worse outcome).
Time frame: baseline, study weeks 1, 8, 9, 10 &12
Reading Comprehension
Reading Comprehension was assessed by child completion of the AIMSWEB curriculum based measure (CBM) test of Reading Comprehension. At baseline (week 1), child's performance was assigned a value of 1.0. The child's performance at weeks 8, 9, 10, and 12 was derived by dividing actual score on the test by the score predicted at that time point after applying the measure's normed "rate of improvement (ROI)" metric to the baseline score. For example, a score of 1.5 at week 8 would indicate that the child's actual score at week 8 was 50% higher than the predicted score at week 8 (which was derived by applying the normed ROI metric to the baseline score). Scores at weeks 8, 9, 10, 12 that are \>1.0 indicate greater improvement than expected (so better outcome), while scores at weeks 8, 9, 10, 12 that are \<1.0 indicate less improvement than expected (so worse outcome).
Time frame: baseline, study weeks 8, 9, 10 &12
Written Expression
Assessed by child completion of the AIMSWEB curriculum based measure (CBM) test of Written Expression, with the measure assessing number of words written by the child after receiving a prompt. At baseline (week 1), child's performance was assigned a value of 1.0. The child's performance at weeks 8, 9, 10, and 12 was derived by dividing actual score (# of words written) on the test by the score predicted at that time point after applying the measure's normed "rate of improvement (ROI)" metric to the baseline score. For example, a score of 1.5 at week 8 would indicate that the child's actual score at week 8 was 50% higher than the predicted score at week 8 (which was derived by applying the normed ROI metric to the baseline score). Scores at weeks 8, 9, 10, 12 that are \>1.0 indicate greater improvement than expected (so better outcome), while scores at weeks 8, 9, 10, 12 that are \<1.0 indicate less improvement than expected (so worse outcome).
Time frame: baseline, study weeks 1, 8, 9, 10 &12