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

• ClinicalTrials.gov Identifier: NCT00794625
• Recruitment Status: Unknown
• First Posted: November 20, 2008
• Last Update Posted: July 16, 2012
• Sponsor: Joseph Blader
• Collaborators: University of Texas; Northwell Health
• Information provided by (Responsible Party): Joseph Blader, National Institute of Mental Health (NIMH)

Tracking Information

• First Submitted Date: November 19, 2008
• First Posted Date: November 20, 2008
• Last Update Posted Date: July 16, 2012
• Study Start Date: November 2008
• Estimated Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 19, 2008): Aggressive behavior [ Time Frame: Measured weekly for 11 to 16 weeks ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: November 19, 2008): ADHD symptoms [ Time Frame: Measured weekly for 11 to 16 weeks ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Attention Deficit Disorder With Hyperactivity

Intervention

• Drug: Valproate
  Standard therapeutic doses of valproate, set according to valproic acid blood level, for 8 weeks
  Other Names:

  • Depakote
  • Valproic acid
• Drug: Risperidone
  Standard therapeutic doses of risperidone for 8 weeks
  Other Name: Risperdal
• Drug: Placebo
  An inactive substance at identical dosing to active treatments for 8 weeks
  Other Names:

  • Inactive substance
  • "Sugar pill"
• Drug: Stimulant medication
  Stimulant medication standard in the care of ADHD, such as methylphenidate or dextroamphetamine
  Other Names:

  • Ritalin
  • Dexedrine
• Behavioral: Behavioral family counseling
  Weekly behavioral counseling with a therapist

Study Arms

• Experimental: 1
  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.
  Interventions:

  • Drug: Valproate
  • Drug: Risperidone
  • Drug: Stimulant medication
  • Behavioral: Behavioral family counseling
• Experimental: 2
  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.
  Interventions:

  • Drug: Valproate
  • Drug: Risperidone
  • Drug: Stimulant medication
  • Behavioral: Behavioral family counseling
• Placebo Comparator: 3
  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.
  Interventions:

  • Drug: Placebo
  • Drug: Stimulant medication
  • Behavioral: Behavioral family counseling

Publications *

• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: November 19, 2008): 270
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 2013
• Estimated Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years to 12 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00794625
• Other Study ID Numbers: R01MH080050( U.S. NIH Grant/Contract ); DSIR 84-CTM
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Joseph Blader, National Institute of Mental Health (NIMH)
• Original Responsible Party: Joseph C. Blader, PhD, Stony Brook University, State University of New York
• Current Study Sponsor: Joseph Blader
• Original Study Sponsor: National Institute of Mental Health (NIMH)

Collaborators

• University of Texas
• Northwell Health

Investigators

• Principal Investigator: Joseph C. Blader, PhD, MSc; Stony Brook University School of Medicine, State University of New York

• PRS Account: National Institute of Mental Health (NIMH)
• Verification Date: July 2012