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.
1. Subjects must be at least 12 years of age but less than 18 when informed consent is
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.
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.
- Drugs that may be used episodically during the trial include nonnarcotic
analgesics, antacids, nonsteroidal anti-inflammatory drugs, antiasthma agents
except steroids, antibiotics, antidiarrheal preparations, antiemetics,
antihistamines, antihypertensives, nonsympathomimetic cold and cough
preparations, cromolyn sodium, diphenhydramine, diuretics, hormones, insulin,
laxatives, and oral hypoglycemic agents.
- Drugs that may be used chronically during the trial include analgesics,
nonsteroidal anti-inflammatory agents, antiasthma agents except steroids,
antibiotics, nonsympathomimetic antihistamines, antihypertensives, cromolyn
sodium, diuretics, hormones, insulin, laxatives, and oral hypoglycemic agents.