Treatment of Mania Symptoms With Drug Therapy - Full Text View

Purpose

This study will determine the effectiveness of three different drug therapies in treating the symptoms of mania.

Condition	Intervention	Phase
Bipolar Disorder Schizophrenia	Drug: Divalproex-extended release (DVP-ER) Drug: Lithium Drug: Quetiapine	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Divalproex Extended Release and Placebo, Lithium, or Quetiapine for Mania

Resource links provided by NLM:

Genetics Home Reference related topics: schizophrenia

MedlinePlus related topics: Bipolar Disorder

Drug Information available for: Lithium carbonate Lithium citrate Quetiapine Quetiapine fumarate

U.S. FDA Resources

Further study details as provided by Palo Alto Veterans Institute for Research:

Primary Outcome Measures:

Reduction in symptoms of mania, as measured by Young Mania Rating Scale [ Time Frame: Measured at baseline and Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Hamilton Rating Scale for Depression [ Time Frame: Measured at baseline and Week 12 ] [ Designated as safety issue: No ]
Clinical Global Impression Scale [ Time Frame: Measured at baseline and Week 12 ] [ Designated as safety issue: No ]
Global Assessment of Functioning [ Time Frame: Measured at baseline and Week 12 ] [ Designated as safety issue: No ]
Lehman Quality of Life scale [ Time Frame: Measured at baseline and Week 12 ] [ Designated as safety issue: No ]


Enrollment:	75
Study Start Date:	February 2005
Study Completion Date:	November 2010
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: DVP + placebo Participants will receive divalproex ER at a therapeutic dose, plus placebo	Drug: Divalproex-extended release (DVP-ER) Divalproex ER will be given in 250 mg or 500 mg tablets. Dosing is once a day, every day, for the duration of study participation, either 12 or 26 weeks. Other Name: depakote ER
Active Comparator: DVP + Quetiapine Participants will receive divalproex ER at a therapeutic dose, plus quetiapine up to 800 mg	Drug: Divalproex-extended release (DVP-ER) Divalproex ER will be given in 250 mg or 500 mg tablets. Dosing is once a day, every day, for the duration of study participation, either 12 or 26 weeks. Other Name: depakote ER Drug: Quetiapine Quetiapine will be dosed to efficacy, provided in 50 mg, 100 mg, 200 mg, or 300 mg pills. Other Name: Seroquel
Active Comparator: DVP + Lithium Participants will receive divalproex ER at a therapeutic dose, plus lithium at a therapeutic blood level	Drug: Divalproex-extended release (DVP-ER) Divalproex ER will be given in 250 mg or 500 mg tablets. Dosing is once a day, every day, for the duration of study participation, either 12 or 26 weeks. Other Name: depakote ER Drug: Lithium Extended release lithium will be provided in 300 mg capsules. Participants will be dosed to a therapeutic blood level of lithium from 0.8 to 1.2 mcg/L. Other Name: Lithobid

Detailed Description:

Mania is a serious condition characterized by extreme excitement, mental and physical hyperactivity, insomnia, and disconnected thoughts. Symptoms of mania are common in patients with schizophrenia or bipolar disorder. When associated with these conditions, mania reaches psychotic proportions and often includes hallucinations, paranoia, and feelings of omnipotence. Such symptoms may put individuals with mania and those around them at risk for physical harm. Drug therapies that can safely and effectively treat symptoms of mania are needed. This study will compare three drug combinations in their ability to treat symptoms of mania in people with schizophrenia or bipolar I disorder.

This study will last 26 weeks and will comprise two parts. In Part 1, participants will be randomly assigned to receive one of three treatments: divalproex-extended release (DV-ER) and lithium, DV-ER and quetiapine, or DV-ER and placebo. Participants will receive their intervention for 12 weeks. Participants will have weekly study visits for the first 4 weeks of Phase 1; biweekly study visits will occur for the following 8 weeks. After Phase 1, participants who have not responded to their drug regimen will complete their participation in the study.

Participants whose symptoms of mania have decreased will be enrolled in Phase 2. During this 14-week continuation phase, participants will continue the drug regimen they began in Phase 1. Participants will have biweekly study visits in Phase 2. During each study visit in Phases 1 and 2, participants will be interviewed about their mania symptoms. Mania, depression, quality of life, and overall functioning scales will assess participants at study entry, at the end of Phase 1, and at the end of Phase 2. Participants over 50 years of age will have an electrocardiogram (EKG) at study entry to determine cardiac function.

Eligibility


Ages Eligible for Study:	18 Years to 65 Years (Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosis of bipolar I disorder or schizophrenia
Experiencing symptoms of mania at study entry
Able to speak and understand English
Willing and able to comply with all study requirements

Exclusion Criteria:

History of partial response or nonresponse to any of the drugs or drug combinations given in this study
History of intolerance to DVP, DVP-ER, lithium, or quetiapine
Disorders that would contraindicate the use of DV, DV-ER, lithium, or quetiapine
Use of antidepressants within 1 month prior to study entry
Use of fluoxetine within 3 months prior to study entry
Impaired cardiac function, as evidenced by abnormal EKG in participants 50 or over
Unstable medical illness within 2 months prior to study entry
At risk for suicide
Substance abuse or dependence within 1 month prior to study entry
Pregnancy, breastfeeding, or plans to become pregnant during the study

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: NCT00183443

Locations


United States, California
Stanford School of Medicine and VA Palo Alto Health Care System
Palo Alto, California, United States, 94304

Sponsors and Collaborators

Palo Alto Veterans Institute for Research

National Institute of Mental Health (NIMH)

Investigators


Principal Investigator:	Trisha Suppes, MD, PhD	Stanford School of Medicine and VA Palo Alto Health Care System

More Information


Responsible Party:	Patricia Suppes, Director, Bipolar and Depression Research Program, National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:	NCT00183443 History of Changes
Other Study ID Numbers:	R01MH069801 DSIR 83-ATSO
Study First Received:	September 13, 2005
Last Updated:	October 8, 2013
Health Authority:	United States: Federal Government

Keywords provided by Palo Alto Veterans Institute for Research:


Mania Manic-depressive Psychotic disorder

Additional relevant MeSH terms:


Schizophrenia Bipolar Disorder Schizophrenia Spectrum and Other Psychotic Disorders Mental Disorders Bipolar and Related Disorders Quetiapine Fumarate Lithium Carbonate Antipsychotic Agents	Tranquilizing Agents Central Nervous System Depressants Physiological Effects of Drugs Psychotropic Drugs Antidepressive Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antimanic Agents

ClinicalTrials.gov processed this record on September 23, 2016