Treatment of Mania Symptoms With Drug Therapy

June 19, 2018 updated by: Patricia Suppes, Palo Alto Veterans Institute for Research

Divalproex Extended Release and Placebo, Lithium, or Quetiapine for Mania

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 comprise a 12-week acute phase and a 14-week continuation phase. While the acute phase is the primary component of this study, the continuation phase will provide extended data on the characteristics and course of responders to the initial treatment combinations. Results from the continuation phase will be reported elsewhere. In the acute phase, 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 the acute phase; biweekly study visits will occur for the following 8 weeks. After the acute phase, 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 offered enrollment in the 14-week continuation phase, during which time participants will continue the drug regimen they began in the acute phase. Participants will have biweekly study visits in the continuation phase. During each study visit in both phases, 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 the acute phase, and at the end of the continuation phase. Participants over 50 years of age will have an electrocardiogram (EKG) at study entry to determine cardiac function.

Study Type

Interventional

Enrollment (Actual)

75

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94304
        • VA Palo Alto Health Care System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • depakote ER
Drug: Quetiapine
Quetiapine will be dosed to efficacy, provided in 50 mg, 100 mg, 200 mg, or 300 mg pills.
Other Names:
  • 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 Names:
  • 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 Names:
  • Lithobid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Symptoms of Mania, as Measured by Young Mania Rating Scale
Time Frame: Week 12
Symptoms of mania, as measured by Young Mania Rating Scale. The scale is eleven-item multiple choice diagnostic questionnaire (range 0-60), which psychiatrists use to measure the severity of manic episodes in children and young adults. Typically, 20 is the minimum score required for mania. Higher scores represent increased severity of mania symptoms.
Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hamilton Rating Scale for Depression (HAM-D,17)
Time Frame: Week 12
The Hamilton Rating Scale for Depression is a multiple item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. The questionnaire is designed for adults and is used to rate the severity of their depression by probing mood, feelings of guilt, suicide ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. The 17-item Likert-type scale (range 0-50) includes eight questions with a 5-point scale (ranging from 0=not present to 4=severe) and nine items scored from 0 to 2. Higher scores indicate increased depression severity. The total sum of these 17 answers is used to arrive at the final score: normal (0-7), mild (8-13), moderate (14-18), severe (19-22), or very severe (>=23).
Week 12
Clinical Global Impression Scale for Bipolar Disorder (CGI-BD)
Time Frame: Week 12
The Clinical Global Impression (CGI) rating scale was modified by Spearing and colleagues (1997) for use in bipolar disorder. CGI scales are measures of symptom severity, treatment response and the efficacy of treatments in treatment studies of patients with mental disorders. The revised CGI-Bipolar Version (CGI-BP) is effective in rating severity of manic and depressive episodes and the degree of change from the immediately preceding phase and from the worst phase of illness. The CGI-BP is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal, not ill) to 7 (very severely ill). Each component of the CGI is rated separately; the instrument does not yield a global score. Only severity of illness scores are reported. Increased scores represent increased illness severity
Week 12
Global Assessment of Functioning
Time Frame: Week 12
The Global Assessment of Functioning (GAF) is a numeric scale used by mental health clinicians and physicians to rate subjectively the social, occupational, and psychological functioning of an individual, e.g., how well one is meeting various problems-in-living. Scores range from 100 (extremely high functioning) to 1 (severely impaired).
Week 12
Social and Occupational Functioning Assessment Scale (SOFAS)
Time Frame: Week 12
The Social and Occupational Functioning Assessment Scale (SOFAS) provides a rating of global social and occupational function independent of clinical symptoms. SOFAS is provided in the Diagnostic and Statistical Manual (DSM-IV) as an Axis V measure. The SOFAS is a global rating of current functioning, which is scored positively on a scale from 0 to 100. Higher scores represent higher levels of functioning. This instrument is a one-item rating of consumer functioning.
Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Palo Alto Veterans Institute for Research

Collaborators

National Institute of Mental Health (NIMH)

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2005

Primary Completion (Actual)

November 1, 2010

Study Completion (Actual)

November 1, 2010

Study Registration Dates

First Submitted

September 13, 2005

First Submitted That Met QC Criteria

September 13, 2005

First Posted (Estimate)

September 16, 2005

Study Record Updates

Last Update Posted (Actual)

July 17, 2018

Last Update Submitted That Met QC Criteria

June 19, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SUP0001AGG/ADO
  • DSIR 83-ATSO (National Institute of Mental Health)
  • R01MH069801 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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