Intuniv vs Placebo in the Treatment of Childhood Intermittent Explosive Disorder
Condition: Intermittent Explosive Disorder; Childhood Aggression; Oppositional Defiant Disorder; Attention Deficit Disorder
MeSH terms: Attention Deficit Disorder with Hyperactivity; Aggression; Attention Deficit and Disruptive Behavior Disorders; Disruptive, Impulse Control, and Conduct Disorders
Intervention: Parent Management Training; Placebo; Intuniv
Intervention description: This is a psychological treatment that focuses on decreasing tantrums and outbursts by reducing the ability of the tantrum to coerce parents into giving in to the demand that precipitated the tantrum.; Weekly dispensation of pills matching Intuniv but without the active medication; Weekly administration of medication in doses as per protocol
Intervention MeSH terms: Guanfacine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 11.0
Sex: All
Minimum age: 6 Years
Maximum age: 12 Years
Healthy volunteers: No
Keywords: childhood; temper; explosive; aggression; tantrums; oppositional; defiant; conduct; disruptive; emotional dysregulation; special education

Summary:

      Children with explosive aggression are often rejected by their peers, placed in special
      classroom, and contribute to family discord. When psychotherapy and family therapy is
      unsuccessful, medications are often used. Current medications are stimulants (e.g.
      methylphenidate, dextroamphetamine), anticonvulsants (e.g. Divalproex) and antipsychotics
      (olanzapine, risperidone). At this time, the available medications are of limited usefulness,
      either because they do not always work or because they have side effects such as weight gain
      or insomnia. There is a clear need for new medications to treat explosive aggression when
      psychotherapy is unsuccessful.

      The hypothesis of this study is the medication Intuniv when combined with psychotherapy will
      be more helpful to children with explosive aggression than placebo combined with
      psychotherapy. Intuniv is a long acting form of guanfacine, a medication approved by the FDA
      for treatment of Attention Deficit Hyperactivity Disorder. Intuniv is not a stimulant, nor is
      it an anticonvulsant, nor is it an antipsychotic.

      The children in this study will be between the ages of 6 and 12 and meet Diagnostic and
      Statistical Manual of Psychiatry Fourth Edition, Text Revision (DSM-IV-TR) criteria for
      Intermittent Explosive Disorder.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 6-12

          2. Meets DSM-IV TR Criteria for Intermittent Explosive Disorder

               1. several discreet episodes of failure to resist aggressive impulses that result in
                  serious assaultive acts or destruction of property

               2. the degree of aggressiveness is grossly out of proportion to any precipitating
                  psychosocial stressors

               3. the aggressive episode is not better accounted for by another mental disorder

               4. duration of at least six months

               5. impairment in home, peer relations and / or school

          3. Modified Overt Aggression Scale (MOAS) score > 15

          4. Parent and child willing to consent to study

          5. Inadequate response to psycho-social interventions (including school interventions)

          6. Medically healthy with

               1. weight > 55 lb (25 kg)

               2. body mass index < 35

               3. normal blood pressure as defined by National Heart Lung and Blood Institute
                  (below 95th percentile for age height and weight)

               4. normal response to orthostatic changes (no persistent fall in systolic/diastolic
                  BP > 20/10 mm Hg within 3 minutes of assuming the upright position)

               5. normal electrocardiogram

               6. normal vital signs

               7. no history of intolerance of guanfacine.

          7. If on another medication, willingness to discontinue if medication is judged
             ineffective after adequate trial or to remain on a constant optimized dose if it is
             partially effective

        Exclusion Criteria:

          1. Current Treatment with another alpha 2 blocker e.g. clonidine

          2. Puberty

          3. Meets criteria for Pervasive Developmental Disorder or Childhood schizophrenia

          4. MOAS score > 50

          5. weight < 55 lb or body mass index > 35

          6. hypertension (Blood Pressure above 95th percentile for age height and weight)

          7. Chronic hypotension (Blood Pressure at or below 5th percentile for age height and
             weight)

          8. Orthostatic Hypotension fall in systolic/diastolic BP > 20/10 mm Hg within 3 minutes
             of assuming the upright position

          9. QTc interval of > 440 milliseconds; Bradycardia; heart block diagnosed

         10. history of seizure during the past 2 years (exclusive of febrile seizures)

         11. Patients who had taken an investigational drug within 28 days

         12. Intelligence Quotient < 70

         13. Physical exam, EKG or laboratory results with any other significant abnormalities
             until reviewed by medicine.

         14. Active suicidal or homicidal ideation or history of suicide attempts

         15. Unequivocal manic or hypomanic Episode

         16. Patients who meet criteria for Major Depression in pre-puberty will not be eligible
             for this study.

         17. Axis I disorders that are current, severe and uncontrolled. Children with moderate
             Axis I pathology will be evaluated on a case by case basis and excluded if the other
             diagnosis is not ADHD but could still be the cause of the temper dyscontrol and the
             treatment is judged substandard.

         18. Any other history of cardiovascular dysfunction

         19. Positive Urine Toxicology

         20. Children who have experienced prior adverse effects (physical or psychological) to
             either Tenex or clonidine

         21. Any child who previously received Tenex and either did not tolerate it, or failed to
             respond to an adequate trial