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

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ClinicalTrials.gov Identifier: NCT00057681

Recruitment Status : Completed

First Posted : April 8, 2003

Results First Posted : March 27, 2013

Last Update Posted : April 4, 2013

Sponsor:

Collaborator:

National Institute of Mental Health (NIMH)

Information provided by (Responsible Party):

Washington University School of Medicine

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Bipolar Disorder	Drug: Lithium carbonate Drug: Valproate Drug: Risperidone	Phase 3

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	379 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Treatment of Early Age Mania (TEAM) Study
Study Start Date :	February 2003
Actual Primary Completion Date :	December 2008
Actual Study Completion Date :	December 2008

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Bipolar disorder

MedlinePlus related topics: Bipolar Disorder

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

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

Clinical Global Impressions-Bipolar Mania Improvement [ Time Frame: Measured at Week 8 ]
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 ]
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 ]
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.

Eligibility Criteria

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Ages Eligible for Study:	6 Years to 15 Years (Child)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00057681

Locations

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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

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

More Information

Publications of Results:

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.

Other Publications:

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.

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

Walkup JT, Wagner KD, Miller L, Yenokyan G, Luby JL, Joshi PT, Axelson DA, Robb A, Salpekar JA, Wolf D, Sanyal A, Birmaher B, Vitiello B, Riddle MA. Treatment of Early-Age Mania: Outcomes for Partial and Nonresponders to Initial Treatment. J Am Acad Child Adolesc Psychiatry. 2015 Dec;54(12):1008-19. doi: 10.1016/j.jaac.2015.09.015. Epub 2015 Oct 8.

Salpekar JA, Joshi PT, Axelson DA, Reinblatt SP, Yenokyan G, Sanyal A, Walkup JT, Vitiello B, Luby JL, Wagner KD, Nusrat N, Riddle MA. Depression and Suicidality Outcomes in the Treatment of Early Age Mania Study. J Am Acad Child Adolesc Psychiatry. 2015 Dec;54(12):999-1007.e4. doi: 10.1016/j.jaac.2015.09.016. Epub 2015 Oct 8.

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.

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Responsible Party:	Washington University School of Medicine
ClinicalTrials.gov Identifier:	NCT00057681
Other Study ID Numbers:	U01MH064846-06 ( U.S. NIH Grant/Contract ) U01MH064846 ( U.S. NIH Grant/Contract ) U01MH064911 ( U.S. NIH Grant/Contract ) U01MH064868 ( U.S. NIH Grant/Contract ) U01MH064887 ( U.S. NIH Grant/Contract ) U01MH064850 ( U.S. NIH Grant/Contract ) U01MH064869 ( U.S. NIH Grant/Contract )
First Posted:	April 8, 2003 Key Record Dates
Results First Posted:	March 27, 2013
Last Update Posted:	April 4, 2013
Last Verified:	March 2013

Keywords provided by Washington University School of Medicine:


Mania

Additional relevant MeSH terms:

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Bipolar Disorder Bipolar and Related Disorders Mental Disorders Valproic Acid Risperidone Lithium Carbonate Serotonin Antagonists Serotonin Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs	Antipsychotic Agents Tranquilizing Agents Central Nervous System Depressants Psychotropic Drugs Dopamine Antagonists Dopamine Agents Antidepressive Agents Enzyme Inhibitors Antimanic Agents Anticonvulsants GABA Agents

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