Risperidone and Divalproex Sodium With MRI Assessment in Pediatric Bipolar

This study has been completed.
Information provided by (Responsible Party):
Mani Pavuluri, University of Illinois at Chicago
ClinicalTrials.gov Identifier:
First received: September 9, 2005
Last updated: November 4, 2015
Last verified: November 2015
The study is to examine the null hypothesis that risperidone and divalproex sodium are equally effective in treating/stabilizing pediatric bipolar disorder.

Condition Intervention Phase
Bipolar Disorder
Drug: Divalproex Sodium
Drug: risperidone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Controlled Trial of Risperidone and Divalproex Sodium With MRI Assessment of Affected Circuitry in Pre and Post Treatment in Pediatric Bipolar

Resource links provided by NLM:

Further study details as provided by University of Illinois at Chicago:

Primary Outcome Measures:
  • Young Mania Rating Scale (YMRS) [ Time Frame: Six week study with assessment at baseline and end of the study (at the end of 6 weeks or earlier if they ended the study before 6 week end point). ] [ Designated as safety issue: No ]
    This measure has 11 items. The purpose of each item is to rate the severity of that abnormality in the patient. A severity rating is assigned to each of the eleven items, based on the patient's subjective report of his or her condition over the previous forty-eight hours and the clinician's behavioral observations during the interview, with the emphasis on the latter. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. Total score of zero to 60 is possible, zero being normal and 60 being severe, 12 serving as a cut off point for illness if equal or above. There are several ways to show change in outcome. We show the mean and standard deviation at week 0 and 6.

Secondary Outcome Measures:
  • Child Depression Rating Scale- Revised (CDRS-R) [ Time Frame: Six week study with assessment at baseline and end of the study (at the end of 6 weeks or earlier if they ended the study before 6 week end point). ] [ Designated as safety issue: No ]
    Response for depressive symptoms was defined as a score less than 40 on the CDRS-R. Range is 18 to 120. Score 18 is normal and higher score signifies depression. The Children's Depression Rating Scale (CDRS) is a 16-item measure used to determine the severity of depression in children 6-18 years of age. Items are measured on 3-, 4-, 5-, and 6-point scales. The mean and standard deviation are measured in this study to illustrate outcome at baseline and when the subject ended the study.

  • Child Mania Rating Scale (CMRS) [ Time Frame: Six week study with assessment at baseline and end of the study (at the end of 6 weeks or earlier if they ended the study before 6 week end point). ] [ Designated as safety issue: No ]
    Child Mania rating scale is a parent rated measure to screen for symptoms of mania. It includes 21 items reflecting the DSM-IV criteria for a manic episode. Each item is answered on a four-point Likert type scale anchored by 0 (Never/Rare), 1 (Sometimes), 2 (Often), and 3 (Very Often). Maximum score possible is 63. Score higher than 20 is considered clinically significant, and this is a dimensional score of manic severity.

  • Clinical Global Improvement in Bipolar Disorder Overall (CGI-BP Overall) [ Time Frame: Six week study with assessment at baseline and end of the study (at the end of 6 weeks or earlier if they ended the study before 6 week end point). ] [ Designated as safety issue: No ]
    Severity of Illness and Global Improvement are rated on a 7-point scale by the clinician. In addition to rating the overall illness with the CGI-BP, severity and improvement are considered on various other dimensions such as mania, depression, attention deficit/hyperactivity, psychosis, aggression and sleep difficulties. Score of 1, 2 and 3 would mean there is clinically observed symptom improvement where 1 is the best outcome than 2 or 3. The point 4 is the point where the subject presents at baseline of that specific individual. If they become worse on clinical symptoms, they are rated as 5, 6 or 7 where 7 is worse than 5.

Enrollment: 65
Study Start Date: April 2003
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Risperidone
Risperidone is an antimanic medication and is a second generation antipsychotic
Drug: risperidone
Risperidone is a second generation antipsychotic and antimanic drug
Other Names:
  • antipsychotic
  • risperdal
Active Comparator: Divalproex sodium
Divalproex sodium is an antiepileptic medication and is a mood stabilizer
Drug: Divalproex Sodium
Divalproex sodium is a mood stabilizer
Other Names:
  • antiepileptic
  • valproic acid

Detailed Description:

Pediatric Bipolar Disorder (PBD) severely impairs a child's emotional development, and is associated with alarming rates of suicide, school failure, aggression, risk taking behaviors and substance abuse (Geller et al, 1998; 2001; Carlson et al, 1998). At present, very little is known about the pathophysiology or optimal treatment of PBD. The long range goals of this proposal are threefold: to investigate a range of pharmacotherapeutic agents that are safe and efficacious for PBD, to use fMRI techniques to examine abnormalities in brain function in this disorder, as well as any change in brain function after treatment.

In contrast to the adult literature, we are aware of only two prospective studies assessing the efficacy of standard mood stabilizers in a pediatric sample. In one, lithium was found to be moderately effective in PBD with comorbid substance abuse (Geller et al, 1998). In the other, divalproex sodium, lithium and carbamazepine produced a maximum of 50% symptom reduction (Kowatch et al, 2000). Subsequently, Kafantaris et al (2001) observed a potentiation of lithium's antimanic effect when combined with risperidone. Further, a prospective, open trial of olanzapine for PBD reported a 70% symptom reduction (Frazier et al, 2001) with a retention rate of 96% compared to only 7% with classic mood stabilizers (Kowatch et al, 2000).

Thus, parallelling adult studies (Sachs et al, 2000), novel antipsychotics are a promising treatment in this population. Further, up to 60% of acute PBD episodes present with psychotic features (Geller et al, in press). Finally, the time to full effect with mood stabilizers is often 4 weeks in children (Kowatch et al, 2000; Geller et al, 1998; Kafantaris et al, 2001), whereas antipsychotics usually have a more rapid response onset (Pavuluri et al, in press). Given the potential efficacy of novel antipsychotics for PBD, the aim is to conduct a randomized trial comparing a novel antipsychotic to a standard mood stabilizer:


Ages Eligible for Study:   10 Years to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Children with Bipolar Disorder
  • Must be able to swallow tablets

Exclusion Criteria:

  • Children with general medical condition such as head injury, epilepsy, endocrine disorders
  • Those who are on mood altering medications such as steroids, and those diagnosed with mental retardation are excluded to avoid confounding and contributing factors to mood swings.
  • If we discover during the interview that the parent and/or child does not understand the consent/assent procedures, we will exclude them.

We expect only a small number of children to be excluded from the study due to exclusionary criteria. Selection of the subjects is not based on sex, race, or ethnic group.

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00176202

United States, Illinois
Neuro Psychiatric Institute (NPI)
Chicago, Illinois, United States, 60612
NPI, University of Illinois at Chicago
Chicago, Illinois, United States, 60612
Chicago, Illinois, United States, 60612
Sponsors and Collaborators
University of Illinois at Chicago
Principal Investigator: Mani Pavuluri, MD University of Ilinois at Chicago
  More Information

No publications provided

Responsible Party: Mani Pavuluri, Director of BRAIN Center, University of Illinois at Chicago
ClinicalTrials.gov Identifier: NCT00176202     History of Changes
Other Study ID Numbers: RIS-BIP-407
Study First Received: September 9, 2005
Results First Received: June 2, 2015
Last Updated: November 4, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mental Disorders
Mood Disorders
Antipsychotic Agents
Valproic Acid
Antimanic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Antagonists
Enzyme Inhibitors
GABA Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Antagonists
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on December 01, 2015