Long Acting Stimulant Treatment of Attention Deficit Hyperactivity Disorder (ADHD) in Young Children

This protocol involves an 8-week, open-label, pilot study evaluating the effectiveness,
safety, and tolerability of Ritalin LA in treating Attention-Deficit/Hyperactivity Disorder
(ADHD) in 4 and 5 year old children. The purpose of this study is to ascertain pilot data on
the use of long-acting stimulants in preschool-age children since virtually no data exist on
these medications in this population. The interventions include utilizing short-acting
methylphenidate for the initial dosing and titration and then converting the children to
Ritalin LA once an optimal dose has been found. Parents will also be receiving parent
education training throughout the study. Evaluations will include obtaining the ADHD-IV at
every visit, side effects of the medication, vital signs, EKG, physical exam, the Clinical
Global Assessment Scale, and the Clinical Global Impression-Improvement and Severity Scales.
This study will also assess parent stress with the Parent Stress Index and the emotional
index of the children with the Expressed Emotion Scale for Children. Follow-up will be weekly
during the first month and bi-weekly during the second month.

Inclusion Criteria:

- Informed consent obtained from the legal guardian.

- Parent and child must be English-speaking.

- The child must have been living with the parent or guardian for a minimum of 6 months
at the time of study entry.

- Age: 4-5 years of age at study entry.

- weight of at least 15kg (20th percentile for 4 year olds) for boys and weight of at
least 14.5kg (20th percentile for 4 year olds) for girls

- Severity: age and sex-adjusted T score greater or equal to 65 on the Hyperactive-
Impulsive Subscale of both the Conners Parent and Teacher Rating Scales (L)

- Diagnosis: meets DSM-IV criteria for ADHD (hyperactive/impulsive or combined subtype),
on Parent Diagnostic Interview Schedule for Children-IV (DISC-IV) and clinical
interview by experienced clinician. ADHD must be the primary disorder.

- Duration: symptoms must have been present for a minimum of nine months.

- Impairment: less than or equal to 55 on the Child Global Assessment Scale.

- Cognitive functioning: An estimated IQ 70 or greater on the Peabody Picture Vocabulary
Test (PPVT).

- School: participation in school-type program at least 2 half-days per week where class
includes at least 8 peers; if child has been expelled from an eligible program in the
3 months before screening, they can be considered for enrollment as this may reflect
severity of the disorder

- Parents and patients must be able to attend regular study visits.

- Children being treated with other stimulant or non-stimulant medications prior to
enrollment will be allowed to discontinue treatment with these medications in order to
enter the study, providing the parent wants to do so to enable their child to have a
trial of Ritalin LA, the target symptoms are not well-controlled or unwanted side
effects are persisting on their current treatment, and the prescribing physician is
notified by the parent. These children will have a visit 1A in order to accommodate a
5 half-lives washout of their pre-study medication.

Exclusion Criteria:

- Other medications: no concurrent psychotropic medications or other medications
(including herbal preparations and over-the-counter medications) with significant CNS
effects (e.g., antidepressants, antipsychotics, drugs affecting blood pressure or
heart rate, anticonvulsants, alpha-agonists, adrenergic blockers, lithium, or sedating
antihistamines).

- General medical conditions: children with major medical conditions that would
interfere with involvement in the study or the study medication will not be enrolled.

- Serious structural cardiac abnormalities: The recent joint advisory of the American
Academy of Pediatrics (AAP) and the American Heart Association (AHA) recommend use of
stimulant medications should generally be avoided in patients with cardiomyopathy,
serious heart rhythm or structural abnormalities, or other serious cardiac problems.
Any patient with such a diagnosis will not be allowed in this study.

- Systolic and diastolic blood pressure above 95th percentile for age and gender

- Exclusionary Psychiatric Conditions: Current Adjustment Disorder, Autism, Psychosis,
Bipolar Disorder, PTSD, significant suicidality, or any other psychiatric disorder in
addition to ADHD that requires treatment with additional medications.

- History of physical, sexual, or emotional abuse that results in a clinically
significant impact on clinical presentation, potentially driving some of the symptoms
of ADHD.

- Prior failure to respond to an adequate trial of any methylphenidate product. This
will be at the determination of the investigator.