Predictors of Improvements in Irritability and Aggression in Children With ADHD Treated With CNS Stimulants

Study Summary

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-ADH

Primary Outcome

Thus study examines response markers for CNS stimulants to improve irritability and to improve aggression. For this second treatment phase comprised of the within subjects crossover of optimal med vs placebo, the primary outcome for irritability is the drug placebo difference in the guardian rated Affective Reactivity Index collected for 7 days over the blinded within subjects crossover phase. ARI has 6 items rated 0-2 for range of - to 14 with higher scores representing greater irritability lev

Conditions Studied

Interventions

• DRUG Placebo
• DRUG CNS Stimulant
• OTHER CNS Stimulant open label first phase

Study Locations (1)