Treatment of Severe Childhood Aggression (The TOSCA Study)
Condition: Attention Deficit Disorder With Hyperactivity
MeSH terms: Attention Deficit Disorder with Hyperactivity; Aggression
Intervention: Methylphenidate HCl; Risperidone; Parent Management Training (PMT); Placebo
Intervention description: For children weighing less than 25 kg, the dose will be titrated at 18 mg for the first 7 days, 36 mg for the next 4 days, and, if needed, 54 mg for the next 4 days. For children weighing more than 25 kg, the dose will be titrated at 18 mg for the first 4 days, 36 mg for the next 3 days, 54 mg for the next 4 days, and 72 mg for the next 3 days.
Once the child's optimal dose is established, he or she will continue on that dose for the rest of the 21-week trial.
One pill is taken once daily.; For children weighing less than 45 kg, the dose will start at 0.5 mg at night. After 4 days, the child's dose may be increased to 1 mg a day. On Day 8, the child's dose may be increased to 1.5 mg a day. On Day 16, the child's dose may be increased to 2.0 mg a day. On Day 22, the child's dose may be increased to 2.5 mg a day.
For children weighing more than 45 kg, the dose will start at 0.5 mg at night. After 4 days, the child's dose may be increased to 1.0 mg a day. On Day 8, the child's dose may be increased to 1.5 mg a day. On Day 12, the child's dose may be increased to 2.0 mg a day. On Day 15, the child's dose may be increased to 2.5 mg a day. On Day 18, the child's dose may be increased to 3 mg a day. On Day 23, the child's dose may be increased to 3.5 mg a day.; PMT will include individual parent sessions held weekly for 9 weeks, with two booster sessions to be completed during the 3-month extension. Sessions will include development of problem-solving skills and behavior management strategies, practice activities, and role-playing with the behavioral therapist.; One pill will be taken once daily for the first 4 days and then twice daily until Week 21.
Intervention MeSH terms: Risperidone; Methylphenidate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 168.0
Sex: All
Minimum age: 6 Years
Maximum age: 12 Years
Healthy volunteers: No
Keywords: Conduct Disorder; Attention Deficit and Disruptive Behavior Disorders

Summary:

      This study will determine the safety and effectiveness of two medications for treating
      aggression in children with attention deficit hyperactivity disorder (ADHD).
    

Eligibility criteria:

        Inclusion Criteria:

          -  DSM-IV diagnosis of ADHD, any subtype

          -  DSM-IV diagnosis of a disruptive behavior disorder, including CD or ODD

          -  Evidence of serious physical aggression, as rated on the Overt Aggression
             Scale-Modified, and as determined by parent or guardian ratings on the NCBRF D-Total
             Score. In addition, the blinded clinician must assign a clinical global impressions
             severity score of 4 or greater for aggression.

          -  Prior to random assignment, participants must be free of all psychotropic medicines
             for 2 weeks for most drugs (such as most antidepressants, alpha agonists, beta
             blockers, anxiolytics, mood stabilizers, and antihistamines), and 4 weeks for depot
             antipsychotics and fluoxetine.

        Exclusion Criteria:

          -  Full-scale IQ below 71

          -  Pregnancy or a history of seizure disorder or other neurological or medical disorders
             for which medication may present a considerable risk

          -  Abnormal liver function

          -  Pervasive developmental disorder, schizophrenia or other psychotic disorders, or
             eating disorders

          -  Currently taking other psychotropic medications from which discontinuation would
             present a significant risk. Participants may not discontinue a satisfactory medication
             to participate.

          -  Presence or history of major depressive disorder

          -  Diagnosis of bipolar disorder

          -  A hypomanic/biphasic score of 36 or greater as rated by child's parent on the General
             Behavior Inventory and confirmed by clinician as indication of mood disorder

          -  Active substance abuse disorder or lack of control of substance use that does not
             allow for safe medication administration

          -  Evidence of current child abuse or neglect

          -  History of suicide attempt in the past year or current suicidal ideation with plan
             and/or intent

          -  Family history of type II diabetes in two or more first degree relatives, defined as
             biological parents and/or full biological siblings