CNS Stimulants for ADHD
Trial Summary
What is the purpose of this trial?
Impulsive Aggression and chronic irritability (IACI) often occur together and are one of the most common reasons children present for behavioral health (BH) care. ADHD frequently associated with IACI as upwards of 50% of youth with ADHD manifest impairing IACI levels. IACI is the most common reason that children with ADHD are prescribed antipsychotics and admitted to inpatient BH units. Systematic dose optimization of CNS stimulants improves levels of IACI, reducing the need for these more intensive and burdensome treatments. However, response varies, with over half of children with ADHD showing meaningful improvement, upwards of 40% receiving minimal benefit and 3 to 10% exhibiting increased IACI levels. Symptom levels of ADHD or IACI and other demographic variables are of limited utility for predicting response, suggesting the need to move beyond symptoms in the search for treatment predictors. Youth with ADHD and IACI struggle with multiple aspects reinforcement learning (RL), defined as learning from interactions with the environment to reach a goal. Successful RL efforts tap multiple cognitive functions. In controlled laboratory tasks, youth with IACI and various BH disorders exhibit excessive behavioral and neural response to receiving reward (reward responsiveness), difficulty processing environmental cues to adapt behavior to meet a goal (set shifting/goal updating) and impaired ability to flexibly attend to relevant stimuli when blocked from a goal (frustrative nonreward). Event related potentials (ERP) are small electrical responses in the brain in response to specific events or stimuli measured by electroencephalogram (EEG) testing. ERPs exist that can serve as established neural measures of each of these cognitive functions offering a child friendly means to assess their contribution to observable levels of IACI. CNS stimulants improve functioning in these specific realms and impact associated ERPs to the degree that differences between ADHD and non-ADHD youth disappear. This study will examine the capacity of these ERPs to predict levels of IACI exhibited by children with ADHD when at home. Investigators will then assess if variability across children in the capacity of CNS stimulants to impact RL associated ERPs accounts for differences in the clinical effects of CNS stimulant medications to improve IACI at home using a multimethod battery integrating ERPs, parent report and task performance. Specifically, investigators will examine variance in the reward positivity (RewP) ERP when receiving reward feedback, the switch positivity (SwP) ERP measuring mental effort when cued to shift set and the change in P3b amplitude measuring attention allocation when transitioning from reward to nonreward on a go-no-go task. To achieve these aims, 136 children with ADHD and elevated IACI levels will have their CNS stimulant dose optimized over six weeks and then complete a two week within subjects crossover trial of placebo versus optimal dose. ERP collection will be completed within each blinded week. Parent ratings will be gathered 3 times per day including during peak and off-peak times of medication efficacy to capture the variance in IACI levels within the day and disentangle reports of worsening IACI related to loss of previously beneficial medication effects versus those most likely related to a direct adverse response to medication.
Will I have to stop taking my current medications?
The trial requires that participants stop taking antipsychotics, mood stabilizers, and other medications that affect EEG data collection, like benzodiazepines.
What evidence supports the effectiveness of CNS stimulants as a drug for treating ADHD?
Research shows that CNS stimulants, like methylphenidate and amphetamine derivatives, are effective in improving school performance, behavior, and social interactions in about 75% of children with ADHD. These drugs are well-tolerated and are the most commonly used treatment for managing ADHD symptoms.12345
Are CNS stimulants safe for humans, especially regarding heart health?
Research shows that CNS stimulants, like those used for ADHD, have been studied for heart safety. Some studies found a slight increase in emergency visits for heart symptoms, but larger studies found no link to serious heart problems like heart attacks or strokes. However, these studies mostly looked at short-term use, so long-term effects are still unclear.26789
How do CNS stimulants differ from other ADHD drugs?
CNS stimulants, like methylphenidate and amphetamine derivatives, are the first-line therapy for ADHD and are unique because they include longer-acting formulations that provide up to 12 hours of symptom control, reducing the need for multiple daily doses and minimizing side effects from rapid concentration changes. Lisdexamfetamine, a novel CNS stimulant, is a prodrug that requires oral administration to activate, which may help prevent abuse.210111213
Eligibility Criteria
This trial is for children with ADHD who show signs of impulsive aggression and chronic irritability. Participants must have elevated levels of these behaviors and will undergo a process to find the best dose of CNS stimulants over six weeks, followed by a two-week test comparing their optimized dose with a placebo.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Open-label Dose Optimization
Participants have their CNS stimulant dose optimized over 6 visits under open label conditions.
Randomized Controlled Trial (RCT)
Participants undergo a 2-week within-subjects crossover trial of optimal dose versus placebo.
Follow-up
Participants are monitored for safety and effectiveness after treatment.
Treatment Details
Interventions
- CNS Stimulant
Find a Clinic Near You
Who Is Running the Clinical Trial?
Milton S. Hershey Medical Center
Lead Sponsor