Treatment of Mania Symptoms With Drug Therapy

Phase 3

Completed

Conditions: Schizophrenia
Bipolar Disorder

Interventions: Drug: Divalproex-extended release (DVP-ER)
Drug: Lithium
Drug: Quetiapine

Registration Number: NCT00183443

Lead Sponsor: Palo Alto Veterans Institute for Research

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

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 75

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DVP + Lithium	Lithium	Participants will receive divalproex ER at a therapeutic dose, plus lithium at a therapeutic blood level
DVP + placebo	Divalproex-extended release (DVP-ER)	Participants will receive divalproex ER at a therapeutic dose, plus placebo
DVP + Quetiapine	Divalproex-extended release (DVP-ER)	Participants will receive divalproex ER at a therapeutic dose, plus quetiapine up to 800 mg
DVP + Lithium	Divalproex-extended release (DVP-ER)	Participants will receive divalproex ER at a therapeutic dose, plus lithium at a therapeutic blood level
DVP + Quetiapine	Quetiapine	Participants will receive divalproex ER at a therapeutic dose, plus quetiapine up to 800 mg

Primary Outcome Measures

Name	Time	Method
Symptoms of Mania, as Measured by Young Mania Rating Scale	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.

Secondary Outcome Measures

Name	Time	Method
Hamilton Rating Scale for Depression (HAM-D,17)	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).
Clinical Global Impression Scale for Bipolar Disorder (CGI-BD)	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
Global Assessment of Functioning	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).
Social and Occupational Functioning Assessment Scale (SOFAS)	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.