Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder

Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood mental
disorders. Children with ADHD have impaired functioning in multiple settings, including home
and school. They also have difficulty relating with peers. If left untreated, the disorder
may cause adverse effects that can last into adolescence and adulthood. Stimulant
medications, such as methylphenidate, are effective in reducing ADHD symptoms on a
short-term basis. However, few long-term benefits in academic or general functioning from
current ADHD therapies have been demonstrated. Focalin XR is a stimulant medication that is
FDA-approved for treating ADHD. Guanfacine is another medication that is currently approved
for the treatment of hypertension, but has long been used for treating ADHD. This study will
determine the effectiveness of a combination of Focalin XR and guanfacine in enhancing
cognitive functioning and improving the long-term benefit of ADHD treatment.

Participants in this study will be randomly assigned to one of three treatment regimens:
Methylphenidate (Focalin XR) and placebo; guanfacine and placebo; or Focalin XR and
guanfacine. The study will be conducted in two phases: an 8-week double-blind treatment
phase and a 12-month open-label treatment phase. In Phase I, one third of participants will
receive placebo for the initial 4 weeks, followed by Focalin XR alone for the remaining 4
weeks. All other participants will receive their assigned medications for the full 8 weeks.
All participants will attend two study visits prior to beginning treatment and one study
visit per week throughout Phase I. At the end of Phase I, treatment assignments will be
unblinded. Participants who experienced adequate improvement with their assigned treatment
will then continue in Phase II on the same medication(s) for an additional 12 months.
Participants will attend study visits once per month until the end of the study. Study
visits will include self-report measures, clinical assessments, and cognitive testing.
Participants will also undergo four electroencephalography (EEG) tests and two fMRI scans
over the course of the study. All Phase II participants will receive a follow-up telephone
call 1 month after the final study visit.

Inclusion Criteria:

- Diagnosis of DSM-IV ADHD by K-SADS-PL and confirmed by clinical interview

- Clinical Global Impression-Severity score of at least 4 for ADHD

- Resided with primary caretaker for at least 6 months prior to study entry

Exclusion Criteria:

- History of autism, pervasive developmental disorder, chronic tic disorder, psychosis,
or bipolar disorder

- Current major depression or panic disorder

- Systolic or diastolic blood pressure at screening greater than the 95th percentile or
less than the 5th percentile for age and body mass index (BMI)

- Any medical condition that might make stimulant or alpha agonist therapy medically
inadvisable

- Need for chronic use of other medications with central nervous system effects

- Pregnant, breastfeeding, or beyond menarche and has a positive urine pregnancy test

- History of structural heart defects, syncope, or fainting while exercising

- Clinically significant cardiac abnormality as determined by echocardiogram (ECG) at
study entry

- Mental retardation as determined by clinical functional assessment and an IQ estimate
of less than 70 based on Wechsler Adult Intelligence Scale (WAIS) subtests