Event Rate and Effects of Stimulants in ADHD

Summary

Stimulants alleviate information processing and task performance deficits in Attention Deficit/Hyperactivity Disorder (ADHD). Long acting formulations of amphetamines such as lisdexamphetamine dimesylate (LDX) are especially valuable as they target the school day and improve classroom performance. Although stimulants have been widely used in treatment of ADHD, the exact mechanism action and effect on task performance is not completely known.

According to the State Regulation Deficit (SRD) model, children with ADHD have difficulty regulating their levels of arousal/activation during tasks in response to the changing demands of the environment. This leads to problems with downregulating overaroused states and upregulating underaroused states. According to this view, stimulants exert their therapeutic effect (in part) by optimising arousal/activation levels - especially during states of underarousal/activation. Arousal/activation levels can also be altered by extrinsic factors such as event rate (ER), e.g., the rate at which information is presented. Multiple studies suggest that very fast and very slow events can both cause problems for individuals with ADHD, related to overarousal and underarousal state respectively. Putting these intrinsic (stimulants) and extrinsic (ERs) factors together leads to the prediction that changing the rate at which information is presented in a task may alter the efficacy of stimulants and affect the optimal stimulant dose level. More specifically, one dose of stimulant that may be optimal on slow ER tasks (as it increases arousal/activation level) may be less effective under high ER tasks because in such a setting arousal/activation level needs to be lowered and not increased further. Adding stimulants to an already overactivated state may exacerbate the associated problems. The implication of this is that a different dose of stimulant will be needed under different environmental conditions for optimal performance. For example, children with ADHD might require different dosage in the classroom setting to optimize performance. In addition, the neuropsychological basis of performance deficits and improvement by ER and stimulants are also unclear. According to the SRD model, the underlying mechanism can be specific problems in motor activation/preparation or effort regulation. Event-related potentials (ERP), pupil size measurements and cardiac measures enable us to see objectively how motor activation/preparation and effort are affected by ER and simulants.

In this study the investigators aim to test these predictions of the SRD model and identify the neurobiological basis of stimulant action.

Conditions

• Attention Deficit Hyperactivity Disorder

Interventions

DRUG

LDX.

In this study 3 different doses of LDX will be used: * 30 mg capsules: 30 mg LDX, equivalent to 8.9 mg of dexamphetamine * 50 mg capsules: 50 mg LDX, equivalent to 14.8 mg of dexamphetamine * 70 mg capsules: 70 mg LDX, equivalent to 20.8 mg of dexamphetamine

DRUG

sugar pill

Children will take once only a placebo capsule during the DBPC phase (phase 4) the morning of the testing. For blinding purpose we will blindfold the children when taking placebo.

DEVICE

computer task (Go/No-Go task)

DEVICE

EEG

event-related potentials (ERP) and heart rate measurements

DEVICE

pupil size measurements (by using eye tracking)

Sponsors & Collaborators

• Fund for Scientific Research, Flanders, Belgium

  collaborator OTHER

• Shire

  collaborator INDUSTRY

• University Ghent

  lead OTHER

Principal Investigators

• Rudy van Coster, MD, PhD · University Hospital, Ghent

• Herbert Roeyers, PhD · University Ghent

• Edmund Sonuga-Barke, PhD · University Ghent

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

7 Years

Max Age

12 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2014-01-31

Primary Completion

2014-01-31

Completion

2014-01-31

Countries

• Belgium

Study Locations