Low-dose vs. Normal-dose Psychostimulants on Executive Functions in Individuals With ADHD

Attention Deficit Hyperactivity Disorders Clinical Trial

Official title: Effects of Low-dose Versus Normal-dose Psychostimulants on Executive Functions in Individuals With Attention-Deficit Hyperactivity Disorder

Status Active, not recruiting

Clinical Trial Summary

This double-blind crossover study aims to compare cognitive performance (e.g., working memory, selective attention and cognitive flexibility) of children ages 6-18 years diagnosed with ADHD of the combined type (ADHD-C) or inattentive-type (ADHD-IA) and currently on > 20 mg/day of psychostimulants (psychostimulants) on: a) their current dose of psychostimulants, vs. b) a lower-dose of psychostimulants (half of their current dose).

The investigators hypothesize that the lower-dose psychostimulants will result in better cognitive performance than moderate-to-high doses of psychostimulants.

Clinical Trial Description

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by attention deficits, hyperactivity, or impulsive actions that are not appropriate for the individuals' age (Barkley 1997). These behavioural issues arise relatively early in life, typically before the age of 12, and continue to persist into adulthood in many cases (Barkley 1997). In school-aged children, ADHD is associated with low academic achievement, poor school performance, anxiety and depression.

Symptoms are divided into inattention (e.g., easily distracted, difficulty focusing on & completing a task), hyperactivity (e.g., constantly in motion, fidgets, squirms, talks non-stop), and impulsivity (e.g., difficult waiting one's turn, interrupting others). Three subtypes of ADHD have been identified: predominantly inattentive (ADHD-I), predominantly hyperactive-impulsive (ADHD-H), and the combined type (ADHD-C).

Psychostimulants in medium to high doses acts to inhibit re-uptake of dopamine by the dopamine transporter (DAT), resulting in increased dopamine concentrations in the synapse. DAT is abundant in the striatum, which is implicated in hyperactivity and impulsivity aspects of ADHD. However, DAT is sparse in prefrontal cortex (PFC), which plays a critical role in subserving executive functions. Executive functions (EFs; also called cognitive control or self-regulation) are a group of processes involved in concentration, focused attention, self-control, cognitive flexibility, problem-solving, and working memory (refs: Diamond, 2013; Jacques & Marcovitch, 2010). Thus the number of high risk alleles of the gene that codes for the dopamine transporter (DAT1) are associated with hyperactivity (which depends on the striatum) but not inattention or EF deficits (which depend on PFC; refs: Jucaite et al., 2005; Waldman et al., 1998.

The action of low doses of psychostimulants has been shown to be different, however. At low doses psychostimulants has been demonstrated to act preferentially on PFC, increasing dopamine release (refs: Berridge et al., 2006; Schmeichel & Berridge, 2013; Spencer et al, 2012). Thus, moderate to high doses of psychostimulants (doses most often prescribed for children and youths with ADHD) probably do not improve PFC function or EFs, or worse, may actually impair cognitive function, leaving a patient feeling more in a daze.

Optimal dosing for psychostimulants in children and youths with ADHD is usually determined by parents' reports of improved behaviour, almost never by performance on cognitive measures. We propose to look at cognitive performance on measures of attention, working memory, planning, etc. in children and youths with ADHD on their current dose of psychostimulants and on half that much (order counterbalanced across participants).

Purpose/Objectives: This double-blind crossover study aims to compare cognitive performance (e.g., working memory, selective attention and cognitive flexibility) of children ages 6-18 years diagnosed with ADHD of the combined type (ADHD-C) or inattentive-type (ADHD-IA) and currently on > 20 mg/day of psychostimulants on their current dose of psychostimulants and on a lower-dose of psychostimulants (half of their current dose), order counterbalanced across subjects.

To give us an estimate of order effects to help us correct for better performance in the 2nd session due simply to taking the same cognitive tests twice (note: the tests are Version A and B), we will also be recruiting healthy volunteers to serve as a control group. This control group will be strictly no intervention.

Hypotheses: The investigators hypothesize that lower-dose psychostimulants will result in better cognitive performance than moderate-to-high doses of psychostimulants. ;

Related Conditions & MeSH terms

• Attention Deficit Disorder with Hyperactivity
• Attention Deficit Hyperactivity Disorders
• Hyperkinesis

• NCT number: NCT02167048
• Study type: Interventional
• Source: University of British Columbia
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: June 2014
• Completion date: December 2024