Treatment of Mania Symptoms With Drug Therapy

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

Detailed Description
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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.

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

Conditions
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Bipolar Disorder, Schizophrenia

Intervention / Treatment
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* Drug: Divalproex-extended release (DVP-ER)
* Drug: Lithium
* Drug: Quetiapine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: DVP + placebo<br>Participants will receive divalproex ER at a therapeutic dose, plus placebo | Drug: Divalproex-extended release (DVP-ER)<br>* 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.<br>* Other names: depakote ER;|
| Active Comparator: DVP + Quetiapine<br>Participants will receive divalproex ER at a therapeutic dose, plus quetiapine up to 800 mg | Drug: Divalproex-extended release (DVP-ER)<br>* 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.<br>* Other names: depakote ER;Drug: Quetiapine<br>* Quetiapine will be dosed to efficacy, provided in 50 mg, 100 mg, 200 mg, or 300 mg pills.<br>* Other names: Seroquel;|
| Active Comparator: DVP + Lithium<br>Participants will receive divalproex ER at a therapeutic dose, plus lithium at a therapeutic blood level | Drug: Divalproex-extended release (DVP-ER)<br>* 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.<br>* Other names: depakote ER;Drug: Lithium<br>* 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.<br>* Other names: Lithobid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptoms of Mania, as Measured by Young Mania Rating Scale | 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) | 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) | 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 | 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) | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mania, Manic-depressive, Psychotic disorder