Clinical trial NCT00794625: Effectiveness of Combined Medication Treatment for Aggression in Children With Attention Deficit With Hyperactivity Disorder (The SPICY Study)
Official title: Adjunctive Treatment With Divalproex or Risperidone for Aggression Refractory to Stimulant Monotherapy Among Children With ADHD
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Attention Deficit Disorder With Hyperactivity
Keywords: Attention-Deficit/Hyperactivity Disorder
Aggressive Behavior
Oppositional Defiant Disorder
Conduct Disorder
Lead sponsor: National Institute of Mental Health (NIMH)
Sponsor class: NIH
Collaborators: name: University of Texas
name: Northwell Health
First posted: 2008-11-20
Enrollment: 270
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Aggressive behavior
timeFrame: Measured weekly for 11 to 16 weeks
Secondary outcomes:
measure: ADHD symptoms
timeFrame: Measured weekly for 11 to 16 weeks
Other outcomes:
Locations:
city: Glen Oaks
country: United States
facility: North Shore - LIJ Health System, Zucker Hillside Hospital
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
affiliation: Stony Brook University School of Medicine, State University of New York
name: Joseph C. Blader, PhD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Blader JC, Pliszka SR, Kafantaris V, Foley CA, Carlson GA, Crowell JA, Bailey BY, Sauder C, Daviss WB, Sinha C, Matthews TL, Margulies DM. Stepped Treatment for Attention-Deficit/Hyperactivity Disorder and Aggressive Behavior: A Randomized, Controlled Trial of Adjunctive Risperidone, Divalproex Sodium, or Placebo After Stimulant Medication Optimization. J Am Acad Child Adolesc Psychiatry. 2021 Feb;60(2):236-251. doi: 10.1016/j.jaac.2019.12.009. Epub 2020 Jan 30.
citation: Blader JC, Pliszka SR, Kafantaris V, Sauder C, Posner J, Foley CA, Carlson GA, Crowell JA, Margulies DM. Prevalence and Treatment Outcomes of Persistent Negative Mood Among Children with Attention-Deficit/Hyperactivity Disorder and Aggressive Behavior. J Child Adolesc Psychopharmacol. 2016 Mar;26(2):164-73. doi: 10.1089/cap.2015.0112. Epub 2016 Jan 8.
citation: Blader JC, Pliszka SR, Kafantaris V, Foley CA, Crowell JA, Carlson GA, Sauder CL, Margulies DM, Sinha C, Sverd J, Matthews TL, Bailey BY, Daviss WB. Callous-unemotional traits, proactive aggression, and treatment outcomes of aggressive children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2013 Dec;52(12):1281-93. doi: 10.1016/j.jaac.2013.08.024. Epub 2013 Sep 25.