Examining Tolerance to CNS Stimulants in ADHD

Florida International University (FIU)

Status and phase: Completed; Phase 4

Conditions: Attention-deficit/Hyperactivity Disorder

Treatments: Drug: Methylphenidate

Study type: Interventional

Funder types: Other

Identifiers

NCT02039908

MH099030

Details and patient eligibility

About

Although stimulant medication is a well-established treatment for ADHD, it is often necessary for doctors to increase the dose over time to maintain the benefits of the medication. While medication can be very effective for improving symptoms of ADHD during the first year of use, it has not been found to significantly improve the long term course of children with ADHD. For example, in large research studies, groups of children who take medication for ten years do not have consistently better academic grades than groups of children who never used medication (individual results will vary from child to child).

In order to help children with ADHD achieve the best possible outcomes, it is important for doctors to study why this happens. One possible reason is development of tolerance to the medication. Tolerance means that a drug's effects decrease when it is taken consistently over time, so that an increased dose is needed to continue showing effects. Some doctors believe that children who take stimulant medication for ADHD develop tolerance to it which would explain why benefits may not persist over time, but no research studies have been done to measure whether this occurs. This study aims to see if children show a tolerance effect to stimulant medication and whether that tolerance can be prevented by taking short breaks from the medication called medication holidays.

Full description

This is an innovative evaluation of tolerance using an objective measure in an analog classroom. Each subject will complete the a 10-minute math test twice a day for three weeks on optimal dose or placebo, and then be crossed over to the other condition. Within-subject drug/placebo differences will be compared over the three weeks of exposure to assess tolerance in the analog setting.

When school commences, 50% of the sample will be randomized to 7-day-a-week (continuous) dosing and 50% to 5-day-a- week (weekend holidays) dosing to examine the efficacy of prescribed weekend drug holidays for combatting need for dose escalations (tolerance) during the school year.

Participants will be assessed monthly to detect deteriorating functioning. Using a standardized protocol, study physicians will increase dose for subjects in either arm who meet defined impairment thresholds. The difference between the two dosing conditions will inform regarding how best to deal with tolerance in clinical application.

Enrollment: 267 patients

Sex: All

Ages: 6 to 12 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of attention-deficit/hyperactivity disorder
• Full Scale IQ above 80

Exclusion criteria

• Psychotropic medications for conditions other than ADHD
• Active medical or psychiatric conditions that could be worsened by stimulants
• Diagnosis of Autism or Asperger's Disorder
• Documented intolerance fo methylphenidate or failed trial of OROS MPH

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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267 participants in 2 patient groups

Methylphenidate 7-day dosing

Active Comparator group

Description:

During the school year, children in this arm will receive 7-day dosing of medication.

Treatment:

Drug: Methylphenidate

Methylphenidate 5-day dosing

Active Comparator group

Description:

During the school year phase, these children will receive 5-day dosing with weekend holidays.

Treatment:

Drug: Methylphenidate