This study will determine whether two new psychostimulant medications are more effective, tolerable, and acceptable than two older medications for treating attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is characterized by impulsiveness, hyperactivity, and inattention. It is seen primarily in children and adolescents and is often treated with psychostimulant medications. Osmotic-release oral system (OROS) methylphenidate, brand name Concerta, and mixed amphetamine salts extended release, brand name Adderall XR, are psychostimulant medications that have shown both efficacy (that they can have therapeutic benefits) and effectiveness (that they typically have therapeutic benefits in practice). Two newer psychostimulant medications-lisdexamfetamine dimesylate, brand name Vyvanse, and methylphenidate transdermal system, brand name Daytrana-have shown efficacy but have not been tested for effectiveness, nor have they been tested head-to-head against the older psychostimulants. This study will test the effectiveness, tolerability (lack of side effects), and acceptability (ease of use for patients) of the two newer psychostimulant medications and compare them to each other and to the two older psychostimulants.

Participation in this study will last 6 weeks, although some treatments may continue past the end of the study. At enrollment, participants will undergo a series of baseline evaluations. These will include interviews and assessments of ADHD symptoms, concurrent psychiatric disorders, medical and psychiatric history, family history of mental illness, risk and protective factors, other treatments, treatment expectancy of both the youth and parent, and vital signs. In consultation with their doctors, participants will be allowed to exclude zero, one, or two of the study medications; if they choose to exclude both of the new ADHD medications, they will not able to participate in the study. Participants will then be randomly assigned to one of the treatments they choose to include. They will receive a prescription for the medication and instructions for how to use it from their doctors; the study protocol does not specify a particular treatment regimen. Participants will undergo a second set of evaluations after 6 weeks of treatment or before, if the treatment ends earlier. This will include interviews and assessments similar to those administered at baseline as well as evaluation of any medication side effects.

Inclusion Criteria:

• Meets DSM-IV diagnostic criteria for ADHD combined, hyperactive/impulsive, or inattentive subtype
• Outpatient at study entry
• Speaks English
• Willing to be randomly assigned to one of the study treatment options as outlined in the protocol
• No known significant history of cardiovascular disorders, including pre-existing congenital heart disease, structural heart disease, known clinically significant electrocardiogram (ECG) abnormality, or other clinically significant cardiac disorder
• Willing to initiate study medication for ADHD within 7 days of the study baseline visit
• May be receiving stable treatment with other drug for a comorbid disorder, defined as no changes in dose or form of drug treatment for at least 2 weeks prior to the study enrollment visit
• May be receiving psychosocial interventions for ADHD or a comorbid disorder, defined as no changes in form of psychosocial treatment for at least 4 weeks prior to the study enrollment visit

Exclusion Criteria:

• Hypersensitivity to study medication
• Inpatient status at study entry
• Currently taking another medication for ADHD, including another psychostimulant, atomoxetine, or bupropion
• Receiving treatment with a tricyclic antidepressant at study enrollment, with the exception of low-dose imipramine for enuresis or amitriptyline for chronic pain
• Received treatment with a monoamine oxidase inhibitor (MAOI) within the past 30 days
• Psychostimulant drug dependence, bipolar disorder, or schizophrenia
• Presence of psychosis
• Severe mental retardation
• Autism or Asperger's syndrome
• Active suicidal ideation
• Unable or unwilling to comply with the protocol
• Demonstrates a lack of benefit from, an intolerance to, or contraindication to psychostimulant medicine
• Presence of other clinically significant medical conditions, including hyperthyroidism, epilepsy or other seizure disorder, any condition for which an increase in blood pressure or heart rate would be problematic, glaucoma or other significant eye disease for which a psychostimulant would be problematic, or pre-existing gastrointestinal obstruction with gastrointestinal narrowing
• Pregnant or positive result of pregnancy test