Effectiveness of Combined Medication Treatment for Aggression in Children With Attention Deficit With Hyperactivity Disorder (The SPICY Study)

Study Overview
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Brief Summary
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This study will determine the advantages and disadvantages of adding one of two different types of drugs to stimulant treatment for reducing aggressive behavior in children with attention deficit with hyperactivity disorder (ADHD).

Detailed Description
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Attention deficit with hyperactivity disorder (ADHD) is a common childhood mental disorder that affects 3% to 5% of all American children. Symptoms of ADHD commonly include inability to focus or exercise normal inhibition, and in some cases, aggressive behavior. Approximately 33% to 50% of children with ADHD develop oppositional defiant disorder (ODD), and about 20% to 40% develop a conduct disorder (CD). These disorders are characterized by defiant, belligerent, and otherwise aggressive behavior. Treatment for ADHD generally includes use of stimulant medications that decrease impulsivity and increase attentiveness, such as methylphenidate (Ritalin) or dextroamphetamine (Dexedrine), but these do not always affect aggression. To treat aggression in ADHD, many physicians prescribe additional medications, including the mood stabilizing medication valproate and the antipsychotic medication risperidone. There is no clinical evidence proving that using multiple types of medications is safe and effective. This study will treat children with ADHD and aggression with a combination of stimulants and antipsychotic or mood stabilizing medications to determine whether the aggressive behaviors and ADHD symptoms are reduced without harmful side effects. This study has two phases. During the first phase, which will last 3 to 6 weeks, participants will be treated with normal ADHD stimulant medications. During the second phase, those whose aggressive behavior is not effectively suppressed by stimulant medication alone will then be randomly assigned to also receive valproate, risperidone, or placebo for 8 weeks. After 8 weeks, children whose aggression persists will be switched from either valproate to risperidone or risperidone to valproate for another 8 weeks. Those on placebo will not switch medications. All participants will attend weekly monitoring visits for 11 to 16 weeks over the course of the study. At these visits, aggression levels and medication side effects will be assessed. Families will also meet with the researchers to discuss the child's progress and will attend behavioral counseling with a therapist.

Official Title
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Adjunctive Treatment With Divalproex or Risperidone for Aggression Refractory to Stimulant Monotherapy Among Children With ADHD

Conditions
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Attention Deficit Disorder With Hyperactivity

Intervention / Treatment
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* Drug: Valproate
* Drug: Risperidone
* Drug: Placebo
* Drug: Stimulant medication
* Behavioral: Behavioral family counseling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presence of ADHD Presence of persistent, clinically significant aggression Presence of ODD or CD Exclusion Criteria: Presence of psychosis Presence of a major developmental disability Presence of a major mood disorder Contraindications to stimulant, valproate, or risperidone treatment

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>During Phase 1, participants will receive a stimulant medication. If they do not respond to the stimulant, they will add valproate and behavioral family counseling to their treatment during Phase 2. If they do not respond to valproate, they will be switched to risperidone. | Drug: Valproate<br>* Standard therapeutic doses of valproate, set according to valproic acid blood level, for 8 weeks<br>* Other names: Valproic acid;Drug: Risperidone<br>* Standard therapeutic doses of risperidone for 8 weeks<br>* Other names: Risperdal;Drug: Stimulant medication<br>* Stimulant medication standard in the care of ADHD, such as methylphenidate or dextroamphetamine<br>* Other names: Dexedrine;Behavioral: Behavioral family counseling<br>* Weekly behavioral counseling with a therapist<br>|
| Experimental: 2<br>During Phase 1, participants will receive a stimulant medication. If they do not respond to the stimulant, they will add risperidone and behavioral family counseling to their treatment during Phase 2. If they do not respond to risperidone, they will switch to valproate. | Drug: Valproate<br>* Standard therapeutic doses of valproate, set according to valproic acid blood level, for 8 weeks<br>* Other names: Valproic acid;Drug: Risperidone<br>* Standard therapeutic doses of risperidone for 8 weeks<br>* Other names: Risperdal;Drug: Stimulant medication<br>* Stimulant medication standard in the care of ADHD, such as methylphenidate or dextroamphetamine<br>* Other names: Dexedrine;Behavioral: Behavioral family counseling<br>* Weekly behavioral counseling with a therapist<br>|
| Placebo Comparator: 3<br>During Phase 1, participants will receive a stimulant medication. If they do not respond to the stimulant, they will add placebo and behavioral family counseling to their treatment during Phase 2. | Drug: Placebo<br>* An inactive substance at identical dosing to active treatments for 8 weeks<br>* Other names: Sugar pill;Drug: Stimulant medication<br>* Stimulant medication standard in the care of ADHD, such as methylphenidate or dextroamphetamine<br>* Other names: Dexedrine;Behavioral: Behavioral family counseling<br>* Weekly behavioral counseling with a therapist<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aggressive behavior |  | Measured weekly for 11 to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ADHD symptoms |  | Measured weekly for 11 to 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Attention-Deficit/Hyperactivity Disorder, Aggressive Behavior, Oppositional Defiant Disorder, Conduct Disorder