Study of Outcome and Safety of Lithium, Divalproex and Risperidone for Mania in Children and Adolescents - Full Text View

Purpose

This study will evaluate the effectiveness of the medications, lithium (Eskalith®), valproate (Depakote®), and risperidone (Risperdal®) in treating children and adolescents with bipolar disorder or symptoms of mania.

Condition	Intervention	Phase
Bipolar Disorder	Drug: Lithium carbonate Drug: Valproate Drug: Risperidone	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Treatment of Early Age Mania (TEAM) Study

Resource links provided by NLM:

MedlinePlus related topics: Bipolar Disorder

Drug Information available for: Valproic acid Lithium carbonate Valproate sodium Lithium citrate Divalproex sodium Risperidone

Genetic and Rare Diseases Information Center resources: Children's Interstitial Lung Disease

U.S. FDA Resources

Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:

Clinical Global Impressions-Bipolar Mania Improvement [ Time Frame: Measured at Week 8 ] [ Designated as safety issue: No ]
The Clinical Global Impressions-Bipolar (CGI-BP) assessment instrument measured improvement in mania, depression, and overall bipolar illness. The primary outcome measure was mania improvement, which measured the change in mania from baseline. Scores were 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse.

Secondary Outcome Measures:

Modified Side Effects Form for Children and Adolescents [ Time Frame: Measured at Week 8 ] [ Designated as safety issue: Yes ]
The Modified Side Effects Form for Children and Adolescents includes 62 potential side effects, with measures of frequency and severity for each item. Frequencies are 0=not present, 1=1-2 days, 2=3-4 days, 3=5-7 days. Severity scores are 0=not present, 1=mild (does not interfere with functioning), 2=moderate (some interference with functioning), 3=severe (functioning is significantly impaired because of side effects). Items for cardiovascular, gastrointestinal, central nervous system, ocular, mouth and nose, genito urinary, dermatology, musculo-skeletal, and other side effects are included. For analyses, side effects that were reported at any frequency and a severity of 2 or greater were considered present.
K-SADS Mania Rating Scale [ Time Frame: Measured at Week 8 ] [ Designated as safety issue: No ]
The K-SADS Mania Rating Scale (KMRS) is comprised of 15 items modified from WASH-U-KSADS items. The individual items are scored on a 1-6 severity scale and then these item scores are summed to create an overall KMRS score. Guidelines for interpretation are as follows: 0-11 = no or minimal mania, 12-17 = mild mania, 18-25 = moderate mania, 26+ = marked or worse mania. The maximum possible score is 64.


Enrollment:	379
Study Start Date:	February 2003
Study Completion Date:	December 2008
Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Participants will receive treatment with lithium for 8 to 16 weeks	Drug: Lithium carbonate Titrated until blood level is 1.1 to 1.3 mEq/L
Experimental: 2 Participants will receive treatment with valproate for 8 to 16 weeks	Drug: Valproate Titrated until blood level is 111 to 125 ug/mL Other Name: Depakote
Experimental: 3 Participants will receive treatment with risperidone for 8 to 16 weeks	Drug: Risperidone Titrated by weight until dose is 2.0 mg BID to 3.0 mg BID Other Name: Risperdal

Detailed Description:

Patients are randomly assigned to receive lithium (Eskalith), valproate (Depakote), or risperidone (Risperdal) for 8 to 16 weeks. They will have weekly visits to monitor their response to the medication. When the study is complete, care will be transferred to the child's treating psychiatrist.

Eligibility


Ages Eligible for Study:	6 Years to 15 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

DSM-IV criteria for bipolar I (manic or mixed) or mania for at least 4 weeks
CGAS less than or equal to 60
Good physical health

Exclusion Criteria:

Schizophrenia or any pervasive developmental disorder
Major medical or neurological disease
History of addiction to illicit substances or alcohol or drug abuse within the last 4 weeks
IQ less than 70
Pregnancy or breast-feeding
Unacceptable methods of contraception
In-patient care at baseline

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00057681

Locations


United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Maryland
Johns Hopkins Medical Center
Baltimore, Maryland, United States, 21287
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110-1093
United States, Pennsylvania
University of Pittsburgh/WPIC
Pittsburgh, Pennsylvania, United States, 15208
United States, Texas
University of Texas
Galveston, Texas, United States, 77555

Sponsors and Collaborators

Washington University School of Medicine

National Institute of Mental Health (NIMH)

Investigators


Principal Investigator:	Barbara Geller, MD	Washington University School of Medicine

More Information

Publications:

Geller B, Luby JL, Joshi P, Wagner KD, Emslie G, Walkup JT, Axelson DA, Bolhofner K, Robb A, Wolf DV, Riddle MA, Birmaher B, Nusrat N, Ryan ND, Vitiello B, Tillman R, Lavori P. A randomized controlled trial of risperidone, lithium, or divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents. Arch Gen Psychiatry. 2012 May;69(5):515-28. doi: 10.1001/archgenpsychiatry.2011.1508. Epub 2012 Jan 2.

Tillman R, Geller B, Klages T, Corrigan M, Bolhofner K, Zimerman B. Psychotic phenomena in 257 young children and adolescents with bipolar I disorder: delusions and hallucinations (benign and pathological). Bipolar Disord. 2008 Feb;10(1):45-55. doi: 10.1111/j.1399-5618.2008.00480.x.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Vitiello B, Riddle MA, Yenokyan G, Axelson DA, Wagner KD, Joshi P, Walkup JT, Luby J, Birmaher B, Ryan ND, Emslie G, Robb A, Tillman R. Treatment moderators and predictors of outcome in the Treatment of Early Age Mania (TEAM) study. J Am Acad Child Adolesc Psychiatry. 2012 Sep;51(9):867-78. doi: 10.1016/j.jaac.2012.07.001. Epub 2012 Jul 31.

Tillman R, Geller B. Diagnostic characteristics of child bipolar I disorder: does the "Treatment of Early Age Mania (team)" sample generalize? J Clin Psychiatry. 2007 Feb;68(2):307-14.


Responsible Party:	Washington University School of Medicine
ClinicalTrials.gov Identifier:	NCT00057681 History of Changes
Other Study ID Numbers:	U01 MH64846-06, U01MH064846, U01MH064911, U01MH064868, U01MH064887, U01MH064850, U01MH064869
Study First Received:	April 4, 2003
Results First Received:	May 29, 2012
Last Updated:	March 27, 2013
Health Authority:	United States: Federal Government

Keywords provided by Washington University School of Medicine:


Mania

Additional relevant MeSH terms:


Risperidone Antipsychotic Agents Central Nervous System Agents Central Nervous System Depressants Dopamine Agents Dopamine Antagonists 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 February 27, 2015

Study of Outcome and Safety of Lithium, Divalproex and Risperidone for Mania in Children and Adolescents (TEAM)