Quetiapine and Concerta in the Treatment for ADHD and Aggressive Behavior.
Condition: Attention Deficit Disorder With Hyperactivity
MeSH terms: Attention Deficit Disorder with Hyperactivity; Aggression
Intervention: Oros Methylphenidate; quetiapine
Intervention description: Oros methylphenidate will be titrated over 3 visits according to the following schedule:
Visit 2 dose of 18 mg QAM
Visit 3 dose of 36mg QAM
Visit 4 dose of 54mg QAM.; Quetiapine will be titrated according to the following schedule as determined by efficacy and safety assessments (See Table 1).
Table 1: Quetiapine Dosing Schedule (subject's required weight = 30-80 kg)
Visit 5 dose of 25mg BID
Visit 6 dose of 50mg BID
Visit 7 dose of 100mg BID
Visit 8 dose of 200mg BID
Visit 9 dose of 300mg BID
Efficacy: For any visit following Visit 5, dosage will remain stable if clinically significant improvement criteria are met.If subjects subsequently fail to meet clinically significant improvement criteria, dose increases will resume at the next level of the dosing schedule.
Intervention MeSH terms: Quetiapine Fumarate; Methylphenidate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 12 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: ADHD-Combined TypeDisruptive behavior Disorder

Summary:

      The primary purpose of this thirteen-week, open-label study is to test the hypothesis that
      quetiapine in combination with Oros methylphenidate will reduce aggressive symptoms in
      children and adolescents who have shown inadequate response to OROS methylphenidate alone.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects must be at least 12 yrs.old but less than 18 when informed consent is
             obtained.

          2. Subjects must meet DSM-IV criteria for ADHD/Combined Type and one of the Disruptive
             Behavior Disorders as diagnosed by clinical interview and confirmed by the
             Kiddie-SADS-PL (K-SADS-PL) semistructured diagnostic interview.

          3. Subjects must have one DSM-IV aggressive feature of Conduct Disorder (CD) as rated on
             the K-SADS-PL including:

               -  initiation of physical fights (CD symptom A2)

               -  use of a weapon to bring harm to others (CD symptom A3)

               -  physical cruelty to people (CD symptom A4) or animals (CD symptom A5)

               -  confrontation stealing (CD symptom A6)

               -  destruction of property (CD symptom A8 or A9).

          4. Subjects must have severe aggressive and ADHD symptoms as indicated by a global CGI
             score of 4 or greater and a RAAPP score of 4 or 5 at Visit 1.

          5. Subjects must have had at least four outbursts per month involving destruction of
             property, verbal aggression, or physical aggression toward others or self during the
             past two months at Visit 1.

          6. Subjects with previous trials of psychostimulants must have had a response
             insufficient to markedly change overall quality of life as defined by a CGI score of 3
             or greater based on interview with the parent.

          7. Subjects must not have taken any medication for the treatment of ADHD or DBD for
             either 5 half-lives of the medication or 28 days (whichever is less) at Visit 1. If
             subjects are currently taking medications for the treatment of ADHD or DBD, the assent
             and consent must be reviewed and signed by the subject and parent/legal guardians
             (Visit 0) before the physician investigator will provide a tapering schedule for
             current medications.

          8. Laboratory results obtained at Visit 1 must be reviewed by a physician by Visit 2 and
             show no significant abnormalities.

          9. Baseline electrocardiogram (ECG) results obtained at Visit 1 must be assessed by a
             physician by Visit 2 and show no significant abnormalities.

        Exclusion Criteria:

          1. Subjects with likely mental retardation as defined as a K-BIT Matrices IQ score of
             less than 70 at Visit 1.

          2. Subjects who meet criteria for bipolar disorder as diagnosed by clinical interview and
             confirmed by the K-SADS-PL at Visit 1.

          3. Subjects with a biological parent or sibling who meets criteria for bipolar disorder.

          4. Subjects who have any history of psychosis.

          5. Subjects who weigh less than 30kg or more than 80kg at study entry.

          6. Female subjects who are pregnant or who are breast-feeding as assessed at Visit 1.

             Postmenarcheal sexually-active females who are not using a clinically acceptable
             method of birth control.

          7. Subjects with a history of any seizure disorder other than febrile seizures.

          8. Subjects with a history of alcohol or drug abuse within the past three months or who
             are currently using alcohol, drugs of abuse, or any prescribed or over-the-counter
             medications in a manner considered abusive by the investigators.

          9. Subjects currently taking any psychotropic medications or who are likely to need
             psychotropic medications during the study as assessed by the physician at Visit 1.

         10. Subjects considered to be at serious suicidal risk.

         11. Subjects taking any medications that are not reviewed and approved by a physician
             investigator. Specific requirements include:

               -  Psychotropic medications other than quetiapine and Concerta may not be used
                  during the trial.

               -  Patients may receive lorazepam or chlorpromazine if needed for severe aggression.
                  These drugs should not be given beyond 24 hours.